221 results on '"Tadmor T"'
Search Results
2. REAL‐LIFE EXPERIENCE WITH RITUXIMAB‐DOSE‐ADJUSTED EPOCH (R‐da‐EPOCH) IN PRIMARY MEDIASTINAL LARGE B‐CELL LYMPHOMA (PMLBCL): A MULTINATIONAL ANALYSIS OF 274 PATIENTS
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Vassilakopoulos, T., primary, Ferhanoglu, B., additional, Horowitz, N., additional, Mellios, Z., additional, Kaynar, L., additional, Zektser, M., additional, Symeonidis, A., additional, Piperidou, A., additional, Giotas, A., additional, Agathocleous, A., additional, Kalpadakis, C., additional, Akay, O., additional, Atalar, S., additional, Katodritou, E., additional, Leonidopoulou, T., additional, Papageorgiou, S., additional, Tadmor, T., additional, Gutwein, O., additional, Karakatsanis, S., additional, Ganzel, C., additional, Karianakis, C., additional, Isenberg, G., additional, Gainaru, G., additional, Vrakidou, E., additional, Palassopoulou, M., additional, Ozgur, M., additional, Siakantaris, M., additional, Paydas, S., additional, Tsirigotis, P., additional, Tsirogianni, M., additional, Hatzimichael, E., additional, Tuglular, T., additional, Chatzidimitriou, C., additional, Megalakaki, E., additional, Kanellias, N., additional, Zikos, P., additional, Koumarianou, A., additional, Gafter‐Gvili, A., additional, Angelopoulou, M., additional, Karmiris, T., additional, and Gurion, R., additional
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- 2023
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3. P1229: RITUXIMAB-DOSE-ADJUSTED EPOCH (R-DA-EPOCH) IN PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA (PMLBCL): REAL-LIFE EXPERIENCE ON 225 PATIENTS FROM 4 COUNTRIES
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Vassilakopoulos, T., primary, Ferhanoglu, B., additional, Horowitz, N. A., additional, Apostolidis, J., additional, Mellios, Z., additional, Kaynar, L., additional, Zektser, M., additional, Symeonidis, A., additional, Piperidou, A., additional, Kalpadaki, C., additional, Akay, O. M., additional, Atalar, S. C., additional, Sayyed, A., additional, Katodritou, E., additional, Leonidopoulou, T., additional, Papageorgiou, S., additional, Tadmor, T., additional, Gutwein, O., additional, Karakatsanis, S., additional, Ganzel, C., additional, Karianakis, G., additional, Isenberg, G., additional, Gainaru, G., additional, Vrakidou, E., additional, Palassopoulou, M., additional, Ozgur, M., additional, Siakantaris, M., additional, Paydas, S., additional, Tsirigotis, P., additional, Tsirogianni, M., additional, Hatzimichael, E., additional, Tuglular, T. F., additional, Chatzidimitriou, C., additional, Liaskas, A., additional, Lefaki, M. A., additional, Kanellias, N., additional, Zikos, P., additional, Koumarianou, A., additional, Gafter-Gvili, A., additional, Angelopoulou, M., additional, Karmiris, T., additional, and Gurion, R., additional
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- 2022
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4. PB1885: THE ROLE OF PET CT IN HAIRY CELL LEUKEMIA
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itchaki, G., primary, gurevich, K., additional, Gorenberg, M., additional, and Tadmor, T., additional
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- 2022
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5. Merkel cell carcinoma, chronic lymphocytic leukemia and other lymphoproliferative disorders: an old bond with possible new viral ties
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Tadmor, T., Aviv, A., and Polliack, A.
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- 2011
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6. RITUXIMAB‐DOSE‐ADJUSTED EPOCH (R‐DA‐EPOCH) IN PRIMARY MEDIASTINAL LARGE B‐CELL LYMPHOMA (PMLBCL): REAL‐LIFE EXPERIENCE ON 190 PATIENTS FROM 3 MEDITERRANEAN COUNTRIES
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Vassilakopoulos, T., primary, Ferhanoglu, B., additional, Horowitz, N., additional, Mellios, Z., additional, Kaynar, L., additional, Zektser, M., additional, Symeonidis, A., additional, Piperidou, A., additional, Kalpadakis, C., additional, Akay, O. M., additional, Atalar, A. C., additional, Katodritou, E., additional, Leonidopoulou, T., additional, Papageorgiou, S., additional, Tadmor, T., additional, Gutwein, O., additional, Karakatsanis, S., additional, Ganzel, C., additional, Karianakis, G., additional, Isenberg, G., additional, Gainaru, G., additional, Vrakidou, E., additional, Palassopoulou, M., additional, Ozgur, M., additional, Siakantaris, M., additional, Paydas, S., additional, Tsirigotis, P., additional, Tsirogianni, M., additional, Hatzimichael, E., additional, Tuglular, T., additional, Chatzidimitriou, C., additional, Megalakaki, E., additional, Kanellias, N., additional, Zikos, P., additional, Koumarianou, A., additional, Gafter‐Gvili, A., additional, Angelopoulou, M., additional, Karmiris, T., additional, and Gurion, R., additional
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- 2021
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7. Frontline treatment with the combination obinutuzumab±chlorambucil for chronic lymphocytic leukemia outside clinical trials: results of a multinational, multicenter study by ERIC and the Israeli CLL study group
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Herishanu Y, Shaulov A, Fineman R, BasiC-Kinda S, Aviv A, Wasik-Szczepanek E, Jaksic O, Zdrenghea M, Greenbaum U, Mandac I, Simkovic M, Morawska M, Benjamini O, Spacek M, Nemets A, Bairey O, Trentin L, Ruchlemer R, Laurenti L, Ciocan O, Doubek M, Shvidel L, Dali N, Miras F, De Meuter A, Dimou M, Mauro F, Coscia M, Bumbea H, Szasz R, Tadmor T, Gutwein O, Gentile M, Scarfo L, Tedeschi A, Sportoletti P, Vazquez E, Marquet J, Assouline S, Papaioannou M, Braester A, Levato L, Gregor M, Rigolin G, Loscertales J, Perez A, Nijziel M, Popov V, Collado R, Slavutsky I, Itchaki G, Ringelstein S, Goldschmidt N, Perry C, Levi S, Polliack A, and Ghia P
- Abstract
In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O±Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del(17p13.1)/TP53mutation were excluded. A total of 437 patients (median age, 75.9years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min)were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95%CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del(11q22.3) and/or IGHV-unmutated], lymph nodes of diameter >5cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del(11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease. This article is protected by copyright. All rights reserved.
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- 2020
8. Primary diffuse large B-cell lymphoma of the breast: looking at pathogenesis, clinical issues and therapeutic options
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Aviv, A., Tadmor, T., and Polliack, A.
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- 2013
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9. The expression of lysyl-oxidase gene family members in myeloproliferative neoplasms
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Tadmor, T., Bejar, J., Attias, D., Mischenko, E., Sabo, E., Neufeld, G., and Vadasz, Z.
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- 2013
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10. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial
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Dimopoulos, M.A. Gay, F. Schjesvold, F. Beksac, M. Hajek, R. Weisel, K.C. Goldschmidt, H. Maisnar, V. Moreau, P. Min, C.K. Pluta, A. Chng, W.-J. Kaiser, M. Zweegman, S. Mateos, M.-V. Spencer, A. Iida, S. Morgan, G. Suryanarayan, K. Teng, Z. Skacel, T. Palumbo, A. Dash, A.B. Gupta, N. Labotka, R. Rajkumar, S.V. Bar, D. Basso, A. Fantl, D. He, S. Horvath, N. Lee, C. Rowlings, P. Taylor, K. Cochrane, T. Kwok, F. Ramanathan, S. Agis, H. Zojer, N. Kentos, A. Offner, F. Van Droogenbroeck, J. Wu, K.L. Maiolino, A. Martinez, G. Zanella, K. Capra, M. Araújo, S. Gregora, E. Pour, L. Scudla, V. Spicka, I. Abildgaard, N. Andersen, N. Jensen, B.A. Helleberg, C. Plesner, T. Salomo, M. Svirskaite, A. Delarue, R. Blau, I. Schieferdecker, A. Teleanu, V. Munder, M. Röllig, C. Salwender, H.-J. Fuhrmann, S. Weisel, K. Duerig, J. Zeis, M. Klein, S. Reimer, P. Schmidt, C. Scheid, C. Mayer, K. Hoffmann, M. Sosada, M. Dimopoulos, A. Delimpasi, S. Kyrtsonis, M.-C. Anagnostopoulos, A. Nagy, Z. Illés, Á. Egyed, M. Borbényi, Z. Mikala, G. Dally, N. Horowitz, N. Gutwein, O. Nemets, A. Vaxman, I. Shvetz, O. Trestman, S. Ruchlemer, R. Nagler, A. Tadmor, T. Rouvio, O. Preis, M. Cavo, M. De Rosa, L. Musto, P. Cafro, A. Tosi, P. Offidani, M. Corso, A. Rossi, G. Liberati, A.M. Bosi, A. Suzuki, K. Nakaseko, C. Ishikawa, T. Matsumoto, M. Nagai, H. Sunami, K. Chou, T. Akashi, K. Takezako, N. Hagiwara, S. Eom, H.S. Jo, D.-Y. Kim, J.S. Lee, J.H. Yoon, S.S. Yoon, D.H. Kim, K. Levin, M.-D. Vellenga, E. Minnema, M. Waage, A. Haukås, E. Grosicki, S. Pluta, A. Robak, T. Marques, H. Bergantim, R. Campilho, F. Chng, W.J. Goh, Y.T. McDonald, A. Rapoport, B. Álvarez Rivas, M.A. De Arriba de La Fuente, F. González Montes, Y. Martin Sanchez, J. Mateos, M.V. Oriol Rocafiguera, A. Rosinol, L. San Miguel, J. Pérez de Oteyza, J. Encinas, C. Alegre-Amor, A. López-Guía, A. Axelsson, P. Carlson, K. Stromberg, O. Hansson, M. Hveding Blimark, C. Mueller, R. Chen, C.-C. Liu, T.-C. Huang, S.-Y. Wang, P.-N. Na Nakorn, T. Prayongratana, K. Unal, A. Goker, H. Sonmez, M. Korenkova, S. Chaidos, A. Oakervee, H. Sati, H. Benjamin, R. Wechalekar, A. Garg, M. Ramasamy, K. Cook, G. Chantry, A. Jenner, M. Buadi, F. Berryman, R. Janakiram, M. TOURMALINE-MM3 study group
- Abstract
Background: Maintenance therapy following autologous stem cell transplantation (ASCT) can delay disease progression and prolong survival in patients with multiple myeloma. Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile. In this study, we aimed to determine the safety and efficacy of ixazomib as maintenance therapy following ASCT. Methods: The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study took place in 167 clinical or hospital sites in 30 countries in Europe, the Middle East, Africa, Asia, and North and South America. Eligible participants were adults with a confirmed diagnosis of symptomatic multiple myeloma according to International Myeloma Working Group criteria who had achieved at least a partial response after undergoing standard-of-care induction therapy followed by high-dose melphalan (200 mg/m2) conditioning and single ASCT within 12 months of diagnosis. Patients were randomly assigned in a 3:2 ratio to oral ixazomib or matching placebo on days 1, 8, and 15 in 28-day cycles for 2 years following induction, high-dose therapy, and transplantation. The initial 3 mg dose was increased to 4 mg from cycle 5 if tolerated during cycles 1–4. Randomisation was stratified by induction regimen, pre-induction disease stage, and response post-transplantation. The primary endpoint was progression-free survival (PFS) by intention-to-treat analysis. Safety was assessed in all patients who received at least one dose of ixazomib or placebo, according to treatment actually received. This trial is registered with ClinicalTrials.gov, number NCT02181413, and follow-up is ongoing. Findings: Between July 31, 2014, and March 14, 2016, 656 patients were enrolled and randomly assigned to receive ixazomib maintenance therapy (n=395) or placebo (n=261). With a median follow-up of 31 months (IQR 27·3–35·7), we observed a 28% reduction in the risk of progression or death with ixazomib versus placebo (median PFS 26·5 months [95% CI 23·7–33·8] vs 21·3 months [18·0–24·7]; hazard ratio 0·72, 95% CI 0·58–0·89; p=0·0023). No increase in second malignancies was noted with ixazomib therapy (12 [3%] patients) compared with placebo (eight [3%] patients) at the time of this analysis. 108 (27%) of 394 patients in the ixazomib group and 51 (20%) of 259 patients in the placebo group experienced serious adverse events. During the treatment period, one patient died in the ixazomib group and none died in the placebo group. Interpretation: Ixazomib maintenance prolongs PFS and represents an additional option for post-transplant maintenance therapy in patients with newly diagnosed multiple myeloma. Funding: Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company. © 2019 Elsevier Ltd
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- 2019
11. PB1869 PERSISTENT COMPLEMENT ACTIVATION IS PROVOKED BY IGG-AGGREGATES IN A SUB-POPULATION OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS
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Michelis, R., primary, Tadmor, T., additional, Barhoum, M., additional, Shehadeh, M., additional, Shvidel, L., additional, Aviv, A., additional, Stemer, G., additional, Dally, N., additional, Rahimi-Levene, N., additional, Yuklea, M., additional, and Braester, A., additional
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- 2019
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12. PS1399 REAL WORLD DATA ON THE EFFICACY AND SAFETY OF DARATUMUMAB FOR TREATMENT OF PATIENTS WITH RELAPSED/REFRACTORY AL AMYLOIDOSIS: A MULTI-SITE RETROSPECTIVE STUDY
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Shragai, T., primary, Gatt, M., additional, Lavie, N., additional, Vaxman, I., additional, Tadmor, T., additional, Rouvio, O., additional, Zektser, M., additional, Levi, S., additional, Avivi, I., additional, and Cohen, Y.C., additional
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- 2019
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13. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS) : a randomised, double-blind, phase 3 study
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Chanan-Khan, Asher, Cramer, Paula, Demirkan, Fatih, Fraser, Graeme, Silva, Rodrigo Santucci, Grosicki, Sebastian, Pristupa, Aleksander, Janssens, Ann, Mayer, Jiri, Bartlett, Nancy L, Dilhuydy, Marie-Sarah, Pylypenko, Halyna, Loscertales, Javier, Avigdor, Abraham, Rule, Simon, Villa, Diego, Samoilova, Olga, Panagiotidis, Panagiots, Goy, Andre, Mato, Anthony, Pavlovsky, Miguel A, Karlsson, Claes, Mahler, Michelle, Salman, Mariya, Sun, Steven, Phelps, Charles, Balasubramanian, Sriram, Howes, Angela, Hallek, Michael, Assouline, S, Bence-Bruckler, I, Buckstein, R, Fraser, G, Larratt, L, Minuk, L, Villa, D, Angevine, A, Bartlett, N, Bixby, D, Caimi, P, Chanan-Khan, A, Craig, M, Forero-Torres, A, Ganguly, S, Goy, A, Heffner, L, Hermann, R, Lansigan, F, Leis, J, Letzer, J, Link, B, Liu, D, McCaul, K, McGuire, E, Skinner, W, Starodub, A, Stuart, R, Thirman, M, Tirumali, N, Yang, J, Janssens, A, Offner, F, Van den Neste, E, Van Hoof, A, Mayer, J, Novak, J, Trneny, M, Cartron, G, Dartigeas, C, Dilhuydy, M, Ghez, D, Haioun, C, Leblond, V, Salles, G, Balser, C, Cramer, P, Dreger, P, Durig, J, Eckart, M, Heinrich, B, Illmer, T, Jentsch-Ullrich, K, Pfreundschuh, M, Schetelig, J, Schlag, R, Soling, U, Stilgenbauer, S, Anagnostopoulos, A, Dimopoulos, A, Panagiotidis, P, Vrakidou, E, Bairey, O, Yehuda, D Ben, Braester, A, Fineman, R, Herishanu, Y, Nagler, A, Ruchlemer, R, Tadmor, T, Grosicki, S, Homenda, W, Jurczak, W, Pluta, A, Woszczyk, D, Espirito Santo, A, Luis, R, Raposo, J, Viveiros, C, Alexeeva, J, Dunaev, Y, Golubeva, M, Khuageva, N, Loginov, A, Lysenko, I, Osmanov, E, Pavlov, V, Pristupa, A, Proydakov, A, Rossiev, V, Samarina, I, Samoilova, O, Serduk, O, Shneider, T, Udovitsa, D, Voloshin, S, Gayoso, J, Gonzalez, M, Gonzalez Barca, E, Hernandez Rivas, J, Jargue, I, Loscertales, J, Karlsson, C, Sender, M, Aktan, M, Arslan, O, Demirkan, F, Ferhanoglu, B, Kaynar, L, Sayinalp, N, Vaural, F, Yagci, M, Dyagil, I, Kaplan, P, Masliak, Z, Oliynyk, H, Popovska, T, Pylypenko, H, Rekhtman, G, Dearden, C, Morley, N, Moss, P, Rule, S, Pavlovsky, M, Riveros, D, Santucci-Silva, R, Romeo, M, Scheliga, A, Salazar, L, Gomez, D, Ramirez, E, and Jung, C
- Subjects
Male ,Medizin ,Gastroenterology ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,immune system diseases ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Atrial Fibrillation ,Bendamustine Hydrochloride ,Aged, 80 and over ,Anemia ,Nausea ,Middle Aged ,3. Good health ,Fludarabine ,Intention to Treat Analysis ,Oncology ,030220 oncology & carcinogenesis ,Ibrutinib ,Retreatment ,Disease Progression ,Rituximab ,Female ,medicine.drug ,Bendamustine ,Adult ,medicine.medical_specialty ,Neutropenia ,Hemorrhage ,Disease-Free Survival ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,Aged ,Performance status ,business.industry ,Adenine ,medicine.disease ,Interim analysis ,Leukemia, Lymphocytic, Chronic, B-Cell ,Thrombocytopenia ,Surgery ,Regimen ,Pyrimidines ,chemistry ,Pyrazoles ,Mantle cell lymphoma ,business ,030215 immunology - Abstract
Most patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma relapse after initial therapy. Bendamustine plus rituximab is often used in the relapsed or refractory setting. We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma.The HELIOS trial was an international, double-blind, placebo-controlled, phase 3 study in adult patients (≥18 years of age) who had active chronic lymphocytic leukaemia or small lymphocytic lymphoma with measurable lymph node disease (1·5 cm) by CT scan, and had relapsed or refractory disease following one or more previous lines of systemic therapy consisting of at least two cycles of a chemotherapy-containing regimen, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate bone marrow, liver, and kidney function. Patients with del(17p) were excluded because of known poor response to bendamustine plus rituximab. Patients who had received previous treatment with ibrutinib or other BTK inhibitors, refractory disease or relapse within 24 months with a previous bendamustine-containing regimen, or haemopoietic stem-cell transplant were also excluded. Patients were randomly assigned (1:1) by a web-based system to receive bendamustine plus rituximab given in cycles of 4 weeks' duration (bendamustine: 70 mg/m(2) intravenously on days 2-3 in cycle 1, and days 1-2 in cycles 2-6; rituximab: 375 mg/m(2) on day 1 of cycle 1, and 500 mg/m(2) on day 1 of cycles 2-6 for a maximum of six cycles) with either ibrutinib (420 mg daily orally) or placebo until disease progression or unacceptable toxicity. Patients were stratified according to whether they were refractory to purine analogues and by number of previous lines of therapy. The primary endpoint was independent review committee (IRC)-assessed progression-free survival. Crossover to ibrutinib was permitted for patients in the placebo group with IRC-confirmed disease progression. Analysis was by intention-to-treat and is continuing for further long-term follow-up. The trial is registered with ClinicalTrials.gov, number NCT01611090.Between Sept 19, 2012, and Jan 21, 2014, 578 eligible patients were randomly assigned to ibrutinib or placebo in combination with bendamustine plus rituximab (289 in each group). The primary endpoint was met at the preplanned interim analysis (March 10, 2015). At a median follow-up of 17 months (IQR 13·7-20·7), progression-free survival was significantly improved in the ibrutinib group compared with the placebo group (not reached in the ibrutinib group (95% CI not evaluable) vs 13·3 months (11·3-13·9) in the placebo group (hazard ratio [HR] 0·203, 95% CI 0·150-0·276; p0·0001). IRC-assessed progression-free survival at 18 months was 79% (95% CI 73-83) in the ibrutinib group and 24% (18-31) in the placebo group (HR 0·203, 95% CI 0·150-0·276; p0·0001). The most frequent all-grade adverse events were neutropenia and nausea. 222 (77%) of 287 patients in the ibrutinib group and 212 (74%) of 287 patients in the placebo group reported grade 3-4 events; the most common grade 3-4 adverse events in both groups were neutropenia (154 [54%] in the ibrutinib group vs 145 [51%] in the placebo group) and thrombocytopenia (43 [15%] in each group). A safety profile similar to that previously reported with ibrutinib and bendamustine plus rituximab individually was noted.In patients eligible for bendamustine plus rituximab, the addition of ibrutinib to this regimen results in significant improvements in outcome with no new safety signals identified from the combination and a manageable safety profile.Janssen ResearchDevelopment.
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- 2016
14. Monocyte count at diagnosis is a prognostic parameter in diffuse large B-cell lymphoma: results from a large multicenter study involving 1191 patients in the pre- and post-rituximab era
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Tadmor, T., primary, Bari, A., additional, Sacchi, S., additional, Marcheselli, L., additional, Liardo, E. V., additional, Avivi, I., additional, Benyamini, N., additional, Attias, D., additional, Pozzi, S., additional, Cox, M. C., additional, Baldini, L., additional, Brugiatelli, M., additional, Federico, M., additional, and Polliack, A., additional
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- 2013
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15. P-287 Infectious events are much more prevalent following a seven compared to five days cycle of azacitidine regardless of patient's age
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Ofran, Y., primary, Filanovsky, K., additional, Gafter-Gvili, A., additional, Vidal, L., additional, Aviv, A., additional, Gatt, M.E., additional, Silbershatz, I., additional, Herishanu, Y., additional, Arad, A., additional, Tadmor, T., additional, Dally, N., additional, Nemets, A., additional, Rouvio, O., additional, Ronson, A., additional, Herzog-Tzarfati, K., additional, Akria, L., additional, Braester, A., additional, Hellmann, I., additional, Yeganeh, S., additional, Nagler, A., additional, Leiba, R., additional, Mittelman, M., additional, and Merkel, D., additional
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- 2013
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16. Cell surface expression of CD25 antigen (surface IL-2 receptor alpha-chain) is not a prognostic marker in chronic lymphocytic leukemia: results of a retrospective study of 281 patients.
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Shvidel L, Braester A, Bairey O, Rahimi-Levene N, Herishanu Y, Tadmor T, Klepfish A, Ruchlemer R, Shtalrid M, Berrebi A, Polliack A, and Israeli CLL Study Group
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- 2012
17. First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia.
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Eichhorst, B., Niemann, C. U., Kater, A. P., Fürstenau, M., von Tresckow, J., Zhang, C., Robrecht, S., Gregor, M., Juliusson, G., Thornton, P., Staber, P. B., Tadmor, T., Lindström, V., da Cunha-Bang, C., Schneider, C., Poulsen, C. B., Illmer, T., Schöttker, B., Nösslinger, T., and Janssens, A.
- Subjects
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CHRONIC lymphocytic leukemia , *VENETOCLAX , *PROGRESSION-free survival , *RITUXIMAB , *DISEASE progression - Abstract
BACKGROUND Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking. METHODS In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine–cyclophosphamide–rituximab or bendamustine–rituximab) or 12 cycles of venetoclax–rituximab, venetoclax–obinutuzumab, or venetoclax–obinutuzumab–ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity, <10−4 [i.e., <1 CLL cell in 10,000 leukocytes]) as assessed by flow cytometry in peripheral blood at month 15 and progression-free survival. RESULTS A total of 926 patients were assigned to one of the four treatment regimens (229 to chemoimmunotherapy, 237 to venetoclax–rituximab, 229 to venetoclax–obinutuzumab, and 231 to venetoclax–obinutuzumab–ibrutinib). At month 15, the percentage of patients with undetectable minimal residual disease was significantly higher in the venetoclax–obinutuzumab group (86.5%; 97.5% confidence interval [CI], 80.6 to 91.1) and the venetoclax–obinutuzumab–ibrutinib group (92.2%; 97.5% CI, 87.3 to 95.7) than in the chemoimmunotherapy group (52.0%; 97.5% CI, 44.4 to 59.5; P<0.001 for both comparisons), but it was not significantly higher in the venetoclax–rituximab group (57.0%; 97.5% CI, 49.5 to 64.2; P=0.32). Three-year progression-free survival was 90.5% in the venetoclax–obinutuzumab–ibrutinib group and 75.5% in the chemoimmunotherapy group (hazard ratio for disease progression or death, 0.32; 97.5% CI, 0.19 to 0.54; P<0.001). Progression-free survival at 3 years was also higher with venetoclax–obinutuzumab (87.7%; hazard ratio for disease progression or death, 0.42; 97.5% CI, 0.26 to 0.68; P<0.001), but not with venetoclax–rituximab (80.8%; hazard ratio, 0.79; 97.5% CI, 0.53 to 1.18; P=0.18). Grade 3 and grade 4 infections were more common with chemoimmunotherapy (18.5%) and venetoclax–obinutuzumab–ibrutinib (21.2%) than with venetoclax–rituximab (10.5%) or venetoclax–obinutuzumab (13.2%). CONCLUSIONS Venetoclax–obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy as first-line treatment in fit patients with CLL. (Funded by AbbVie and others; GAIA–CLL13 ClinicalTrials.gov number, NCT02950051. opens in new tab; EudraCT number, 2015-004936-36. opens in new tab.) [ABSTRACT FROM AUTHOR]
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- 2023
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18. Hairy cell leukemia and COVID-19 adaptation of treatment guidelines
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Francesco Forconi, Jae H. Park, Martin S. Tallman, Brunangelo Falini, Robert J. Kreitman, James B. Johnston, Sameer A. Parikh, Timothy G. Call, Xavier Troussard, Seema A. Bhat, James S. Blachly, Sasha Dietrich, Gerard Lozanski, Matthew Cross, Jacqueline C. Barrientos, Thorsten Zenz, Claire Dearden, Sunil Iyengar, Alan Saven, Francesco Lauria, Judit Demeter, Gunnar Juliusson, Tadeusz Robak, Douglas E. Gladstone, Versha Banerji, Kerry A. Rogers, Enrico Tiacci, Tamar Tadmor, Pier Luigi Zinzani, John F. Seymour, Farhad Ravandi, Bernhard Wörmann, Constantine S. Tam, Michael R. Grever, Aaron Polliack, Alessandro Gozzetti, Clive S. Zent, Eric H. Kraut, Leslie A. Andritsos, Grever M., Andritsos L., Banerji V., Barrientos J.C., Bhat S., Blachly J.S., Call T., Cross M., Dearden C., Demeter J., Dietrich S., Falini B., Forconi F., Gladstone D.E., Gozzetti A., Iyengar S., Johnston J.B., Juliusson G., Kraut E., Kreitman R.J., Lauria F., Lozanski G., Parikh S.A., Park J., Polliack A., Ravandi F., Robak T., Rogers K.A., Saven A., Seymour J.F., Tadmor T., Tallman M.S., Tam C.S., Tiacci E., Troussard X., Zent C., Zenz T., Zinzani P.L., and Wormann B.
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Cancer Research ,medicine.medical_specialty ,Consensus ,Hairy Cell ,medicine.medical_treatment ,Diseases ,Consensu ,Review Article ,Disease ,Severity of Illness Index ,Internal medicine ,medicine ,Leukaemia ,Humans ,Hairy cell leukemia ,Intensive care medicine ,Cladribine ,Pandemics ,Leukemia, Hairy Cell ,Leukemia ,Hematology ,Pandemic ,SARS-CoV-2 ,business.industry ,Standard treatment ,COVID-19 ,Immunosuppression ,Practice Guidelines as Topic ,medicine.disease ,Oncology ,business ,Human ,medicine.drug - Abstract
Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients. The new recommendations adapt the 2017 consensus for the diagnosis and management with cHCL to the current COVID-19 pandemic. They underline the option of active surveillance in patients with low but stable blood counts, consider the use of targeted and non-immunosuppressive agents as first-line treatment for cHCL, and give recommendations on preventive measures against COVID-19.
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- 2021
19. COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study
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Ellen van der Spek, Emili Montserrat, Talha Munir, Paolo Ghia, Shaimaa El-Ashwah, Andreas Glenthøj, Viola Maria Popov, Sanne H. Tonino, Ann Janssens, Michel van Gelder, Lara Malerba, Rocío García-Serra, Alberto Lopez-Garcia, Juan-Gonzalo Correa, Christos Demosthenous, Idanna Innocenti, Maria Papaioannou, Lydia Scarfò, Antonio Cuneo, Francesca Romana Mauro, Sabina Kersting, Robin Foà, David Donaldson, Livio Trentin, Roberta Murru, Panagiotis Baliakas, Marina Motta, Deepesh Lad, Yervand K Hakobyan, Paolo Sportoletti, Lucrecia Yáñez San Segundo, Alicia Enrico, Elżbieta Kalicińska, Ewa Wasik-Szczepanek, Martin Spacek, Tamar Tadmor, Enrico Lista, Roel van Kampen, Lorella Orsucci, Michael Doubek, Yair Herishanu, Blanca Espinet, Jose Angel Hernandez-Rivas, Inga Piskunova, Ozren Jakšić, Georgios Karakatsoulis, Tomasz Wróbel, Oana Stanca, Luca Laurenti, Martin Andres, Roberto Marasca, Mark-David Levin, Giovanni Del Poeta, Miguel Arturo Pavlovsky, Maria Dimou, Monia Marchetti, Ivana Milosevic, Gianluigi Reda, Tobias Herold, David Allsup, Raul Cordoba, Andrea Visentin, Maria Gomes da Silva, Angela Ferrari, Antonella Capasso, Juan Marquet, Francesca Maria Quaglia, Candida Vitale, Mattias Mattsson, Marta Coscia, Moritz Fürstenau, Lucia Farina, Niki Stavroyianni, Marta Morawska, Arnon P. Kater, Mónica Baile, Gevorg Saghumyan, Carolina Cuéllar-García, Jacopo Olivieri, Darko Antic, Raquel Nunes Rodrigues, Alejandro Alonso Cabrero, Henrik Frederiksen, Alessandro Rambaldi, Marzia Varettoni, Amit Shrestha, Оlga B Kalashnikova, Thomas Chatzikonstantinou, José A. García-Marco, Martin Simkovic, Linda Katharina Karlsson, Odit Gutwein, Mohamed A. Yassin, Rosa Ruchlemer, Eva Gimeno, Kristian Qvist, Fatima Miras, Gilad Itchaki, Maria Rosaria De Paolis, Maria Efstathopoulou, Doreen te Raa, Barbara Eichhorst, Dominique Bron, Jorge Labrador, Gian Matteo Rigolin, Myriam Foglietta, Massimo Gentile, Sofia Chatzileontiadou, Carsten Utoft Niemann, Anargyros Kapetanakis, Kostas Stamatopoulos, Lorenzo De Paoli, Giulia Quaresmini, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Hematologie (9), Chatzikonstantinou, T., Kapetanakis, A., Scarfo, L., Karakatsoulis, G., Allsup, D., Cabrero, A. A., Andres, M., Antic, D., Baile, M., Baliakas, P., Bron, D., Capasso, A., Chatzileontiadou, S., Cordoba, R., Correa, J. -G., Cuellar-Garcia, C., De Paoli, L., De Paolis, M. R., Del Poeta, G., Demosthenous, C., Dimou, M., Donaldson, D., Doubek, M., Efstathopoulou, M., Eichhorst, B., El-Ashwah, S., Enrico, A., Espinet, B., Farina, L., Ferrari, A., Foglietta, M., Frederiksen, H., Furstenau, M., Garcia-Marco, J. A., Garcia-Serra, R., Gentile, M., Gimeno, E., Glenthoj, A., Gomes da Silva, M., Gutwein, O., Hakobyan, Y. K., Herishanu, Y., Hernandez-Rivas, J. A., Herold, T., Innocenti, I., Itchaki, G., Jaksic, O., Janssens, A., Kalashnikova, Оb., Kalicinska, E., Karlsson, L. K., Kater, A. P., Kersting, S., Labrador, J., Lad, D., Laurenti, L., Levin, M. -D., Lista, E., Lopez-Garcia, A., Malerba, L., Marasca, R., Marchetti, M., Marquet, J., Mattsson, M., Mauro, F. R., Milosevic, I., Miras, F., Morawska, M., Motta, M., Munir, T., Murru, R., Niemann, C. U., Rodrigues, R. N., Olivieri, J., Orsucci, L., Papaioannou, M., Pavlovsky, M. A., Piskunova, I., Popov, V. M., Quaglia, F. M., Quaresmini, G., Qvist, K., Reda, G., Rigolin, G. M., Ruchlemer, R., Saghumyan, G., Shrestha, A., Simkovic, M., Spacek, M., Sportoletti, P., Stanca, O., Stavroyianni, N., Tadmor, T., Te Raa, D., Tonino, S. H., Trentin, L., Van Der Spek, E., van Gelder, M., van Kampen, R., Varettoni, M., Visentin, A., Vitale, C., Wasik-Szczepanek, E., Wrobel, T., San Segundo, L. Y., Yassin, M., Coscia, M., Rambaldi, A., Montserrat, E., Foa, R., Cuneo, A., Stamatopoulos, K., Ghia, P., Experimental Immunology, Clinical Haematology, AII - Cancer immunology, and CCA - Cancer Treatment and Quality of Life
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Chronic lymphocytic leukaemia ,Cancer Research ,medicine.medical_specialty ,COVID-19 Vaccines ,Coronavirus disease 2019 (COVID-19) ,Epidemiology ,medicine.medical_treatment ,Chronic lymphocytic leukemia ,CLL, COVID-19 ,610 Medicine & health ,Disease ,Lower risk ,COVID-19 (Malaltia) ,Severity of Illness Index ,Article ,NO ,law.invention ,Risk Factors ,law ,Internal medicine ,Case fatality rate ,Mortalitat ,medicine ,Humans ,Hematologi ,Chronic ,Mortality ,Science & Technology ,Leukemia ,SARS-CoV-2 ,business.industry ,Vaccination ,B-Cell ,Leucèmia ,COVID-19 ,Immunosuppression ,Hematology ,Prognosis ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Survival Analysis ,Intensive care unit ,Lymphocytic ,Oncology ,business ,Life Sciences & Biomedicine - Abstract
Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p
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- 2021
20. Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group
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Rosa Ruchlemer, Angeles Medina Perez, Ariel Aviv, Alessandra Tedeschi, Sandra Bašić-Kinda, Sarit Assouline, Marta Morawska, Mihnea Zdrenghea, Maria Papaioannou, Gilad Itchaki, Viola Maria Popov, Odit Gutwein, Rosa Collado, Michael Gregor, Horia Bumbea, Inga Mandac, Livio Trentin, Neta Goldschmidt, Paolo Sportoletti, Adir Shaulov, Marta Coscia, Gian Matteo Rigolin, Anatoly Nemets, Francesca Romana Mauro, Róbert Szász, Nagib Dali, Fatima Miras, Massimo Gentile, Shimrit Ringelstein, Martin Simkovic, Martin Spacek, Uri Greenbaum, Aaron Polliack, Lydia Scarfò, Michael Doubek, Riva Fineman, Andrei Braester, Lev Shvidel, M.R. Nijziel, Irma Slavutsky, Tamar Tadmor, Eva Gimeno Vázquez, Yair Herishanu, Juan Marquet, Ozren Jakšić, Shai Levi, Ohad Benjamini, Javier Loscertales, Oana Stanca Ciocan, Paolo Ghia, Luciano Levato, Chava Perry, Maria Dimou, Anne De Meûter, Ewa Wasik-Szczepanek, Luca Laurenti, Osnat Bairey, Herishanu, Y., Shaulov, A., Fineman, R., Basic-Kinda, S., Aviv, A., Wasik-Szczepanek, E., Jaksic, O., Zdrenghea, M., Greenbaum, U., Mandac, I., Simkovic, M., Morawska, M., Benjamini, O., Spacek, M., Nemets, A., Bairey, O., Trentin, L., Ruchlemer, R., Laurenti, L., Stanca Ciocan, O., Doubek, M., Shvidel, L., Dali, N., Miras, F., De Meuter, A., Dimou, M., Mauro, F. R., Coscia, M., Bumbea, H., Szasz, R., Tadmor, T., Gutwein, O., Gentile, M., Scarfo', L., Tedeschi, A., Sportoletti, P., Gimeno Vazquez, E., Marquet, J., Assouline, S., Papaioannou, M., Braester, A., Levato, L., Gregor, M., Rigolin, G. M., Loscertales, J., Medina Perez, A., Nijziel, M. R., Popov, V. M., Collado, R., Slavutsky, I., Itchaki, G., Ringelstein, S., Goldschmidt, N., Perry, C., Levi, S., Polliack, A., and Ghia, P.
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obinutuzumab ,Oncology ,Male ,chemistry.chemical_compound ,0302 clinical medicine ,Obinutuzumab ,Monoclonal ,Antineoplastic Combined Chemotherapy Protocols ,80 and over ,Chronic ,Humanized ,chronic lymphocytic leukemia, obinutuzumab, chlorambucil ,Aged, 80 and over ,Leukemia ,Hematology ,Lymphocytic ,3. Good health ,Survival Rate ,030220 oncology & carcinogenesis ,Ibrutinib ,Female ,Aged ,Antibodies, Monoclonal, Humanized ,Chlorambucil ,Chromosomes, Human, Pair 17 ,Disease-Free Survival ,Humans ,Retrospective Studies ,Tumor Suppressor Protein p53 ,Chromosome Deletion ,Leukemia, Lymphocytic, Chronic, B-Cell ,IGHV@ ,medicine.drug ,Human ,medicine.medical_specialty ,chronic lymphocytic leukemia ,chlorambucil ,Antibodies ,Chromosomes ,NO ,03 medical and health sciences ,Internal medicine ,medicine ,Progression-free survival ,Survival rate ,Venetoclax ,business.industry ,Pair 17 ,B-Cell ,Clinical trial ,Settore MED/15 - MALATTIE DEL SANGUE ,chemistry ,business ,030215 immunology - Abstract
In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a “real-world” setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a “real-world” setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.
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- 2020
21. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial
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Meletios A Dimopoulos, Francesca Gay, Fredrik Schjesvold, Meral Beksac, Roman Hajek, Katja Christina Weisel, Hartmut Goldschmidt, Vladimir Maisnar, Philippe Moreau, Chang Ki Min, Agnieszka Pluta, Wee-Joo Chng, Martin Kaiser, Sonja Zweegman, Maria-Victoria Mateos, Andrew Spencer, Shinsuke Iida, Gareth Morgan, Kaveri Suryanarayan, Zhaoyang Teng, Tomas Skacel, Antonio Palumbo, Ajeeta B Dash, Neeraj Gupta, Richard Labotka, S Vincent Rajkumar, Daniel Bar, Alfredo Basso, Dorotea Fantl, Simon He, Neomi Horvath, Cindy Lee, Phillip Rowlings, Kerry Taylor, Tara Cochrane, Fiona Kwok, Sundreswran Ramanathan, Hermine Agis, Niklas Zojer, Alain Kentos, Fritz Offner, Jan Van Droogenbroeck, Ka Lung Wu, Angelo Maiolino, Gracia Martinez, Karla Zanella, Marcelo Capra, Sérgio Araújo, Evzen Gregora, Ludek Pour, Vlastimil Scudla, Ivan Spicka, Niels Abildgaard, Niels Andersen, Bo Amdi Jensen, Carsten Helleberg, Torben Plesner, Morten Salomo, Asta Svirskaite, Richard Delarue, Igor Blau, Aneta Schieferdecker, Veronica Teleanu, Markus Munder, Christoph Röllig, Han-Juergen Salwender, Stephan Fuhrmann, Katja Weisel, Jan Duerig, Matthias Zeis, Stefan Klein, Peter Reimer, Christian Schmidt, Christof Scheid, Karin Mayer, Martin Hoffmann, Markus Sosada, Athanasios Dimopoulos, Sosana Delimpasi, Mary-Christine Kyrtsonis, Achilleas Anagnostopoulos, Zsolt Nagy, Árpád Illés, Miklós Egyed, Zita Borbényi, Gabor Mikala, Najib Dally, Netanel Horowitz, Odit Gutwein, Anatoly Nemets, Iuliana Vaxman, Olga Shvetz, Svetlana Trestman, Rosa Ruchlemer, Arnon Nagler, Tamar Tadmor, Ory Rouvio, Meir Preis, Michele Cavo, Luca De Rosa, Pellegrino Musto, Anna Cafro, Patrizia Tosi, Massimo Offidani, Alessandro Corso, Giuseppe Rossi, Anna Marina Liberati, Alberto Bosi, Kenshi Suzuki, Chiaki Nakaseko, Takayuki Ishikawa, Morio Matsumoto, Hirokazu Nagai, Kazutaka Sunami, Takaaki Chou, Koichi Akashi, Naoki Takezako, Shotaro Hagiwara, Hyeon Seok Eom, Deog-Yeon Jo, Jin Seok Kim, Jae Hoon Lee, Sung Soo Yoon, Dok Hyun Yoon, Kihyun Kim, Mark-David Levin, Edo Vellenga, Monique Minnema, Anders Waage, Einar Haukås, Sebastian Grosicki, Andrzej Pluta, Tadeusz Robak, Herlander Marques, Rui Bergantim, Fernando Campilho, Wee Joo Chng, Yeow Tee Goh, Andrew McDonald, Bernado Rapoport, Miguel Angel Álvarez Rivas, Felipe De Arriba de La Fuente, Yolanda González Montes, Jesus Martin Sanchez, Maria Victoria Mateos, Albert Oriol Rocafiguera, Laura Rosinol, Jesús San Miguel, Jaime Pérez de Oteyza, Cristina Encinas, Adrian Alegre-Amor, Ana López-Guía, Per Axelsson, Kristina Carlson, Olga Stromberg, Markus Hansson, Cecile Hveding Blimark, Rouven Mueller, Chih-Cheng Chen, Ta-Chih Liu, Shang-Yi Huang, Po-Nan Wang, Thanyaphong Na Nakorn, Kannadit Prayongratana, Ali Unal, Hakan Goker, Mehmet Sonmez, Sybiryna Korenkova, Aristeidis Chaidos, Heather Oakervee, Hamdi Sati, Reuben Benjamin, Ashutosh Wechalekar, Mamta Garg, Karthik Ramasamy, Gordon Cook, Andrew Chantry, Matthew Jenner, Francis Buadi, Robert Berryman, Murali Janakiram, Takeda Pharmaceutical Company, Dimopoulos MA1, Gay F2, Schjesvold F3, Beksac M4, Hajek R5, Weisel KC6, Goldschmidt H7, Maisnar V8, Moreau P9, Min CK10, Pluta A11, Chng WJ12, Kaiser M13, Zweegman S14, Mateos MV15, Spencer A16, Iida S17, Morgan G18, Suryanarayan K19, Teng Z19, Skacel T19, Palumbo A20, Dash AB19, Gupta N19, Labotka R19, Rajkumar SV21, TOURMALINE-MM3 study group. Bar D, Basso A, Fantl D, He S, Horvath N, Lee C, Rowlings P, Taylor K, Spencer A, Cochrane T, Kwok F, Ramanathan S, Agis H, Zojer N, Kentos A, Offner F, Van Droogenbroeck J, Wu KL, Maiolino A, Martinez G, Zanella K, Capra M, Araújo S, Gregora E, Hajek R, Maisnar V, Pour L, Scudla V, Spicka I, Abildgaard N, Andersen N, Jensen BA, Helleberg C, Plesner T, Salomo M, Svirskaite A, Delarue R, Moreau P, Blau I, Goldschmidt H, Schieferdecker A, Teleanu V, Munder M, Röllig C, Salwender HJ, Fuhrmann S, Weisel K, Duerig J, Zeis M, Klein S, Reimer P, Schmidt C, Scheid C, Mayer K, Hoffmann M, Sosada M, Dimopoulos A, Delimpasi S, Kyrtsonis MC, Anagnostopoulos A, Nagy Z, Illés Á, Egyed M, Borbényi Z, Mikala G, Dally N, Horowitz N, Gutwein O, Nemets A, Vaxman I, Shvetz O, Trestman S, Ruchlemer R, Nagler A, Tadmor T, Rouvio O, Preis M, Gay F, Cavo M, De Rosa L, Musto P, Cafro A, Tosi P, Offidani M, Corso A, Rossi G, Liberati AM, Bosi A, Suzuki K, Iida S, Nakaseko C, Ishikawa T, Matsumoto M, Nagai H, Sunami K, Chou T, Akashi K, Takezako N, Hagiwara S, Eom HS, Jo DY, Kim JS, Lee JH, Min CK, Yoon SS, Yoon DH, Kim K, Zweegman S, Levin MD, Vellenga E, Minnema M, Schjesvold F, Waage A, Haukås E, Grosicki S, Pluta A, Robak T, Marques H, Bergantim R, Campilho F, Chng WJ, Goh YT, McDonald A, Rapoport B, Álvarez Rivas MA, De Arriba de La Fuente F, González Montes Y, Martin Sanchez J, Mateos MV, Oriol Rocafiguera A, Rosinol L, San Miguel J, Pérez de Oteyza J, Encinas C, Alegre-Amor A, López-Guía A, Axelsson P, Carlson K, Stromberg O, Hansson M, Hveding Blimark C, Mueller R, Chen CC, Liu TC, Huang SY, Wang PN, Na Nakorn T, Prayongratana K, Beksac M, Unal A, Goker H, Sonmez M, Korenkova S, Chaidos A, Oakervee H, Sati H, Benjamin R, Wechalekar A, Garg M, Kaiser M, Ramasamy K, Cook G, Chantry A, Jenner M, Buadi F, Berryman R, Janakiram M., Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), CCA - Cancer Treatment and quality of life, CCA - Imaging and biomarkers, CCA - Cancer biology and immunology, and Hematology
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Male ,Time Factors ,DIAGNOSED MULTIPLE-MYELOMA ,Clinical Trial, Phase III ,Administration, Oral ,030204 cardiovascular system & hematology ,Ixazomib ,chemistry.chemical_compound ,0302 clinical medicine ,Autologous stem-cell transplantation ,Maintenance therapy ,Clinical endpoint ,030212 general & internal medicine ,Non-U.S. Gov't ,Boron Compounds/administration & dosage ,IMPROVES SURVIVAL ,INDUCTION ,Research Support, Non-U.S. Gov't ,General Medicine ,CHEMOTHERAPY ,Middle Aged ,Clinical Trial ,DEXAMETHASONE ,Antineoplastic Agents/administration & dosage ,Multicenter Study ,Treatment Outcome ,Administration ,Randomized Controlled Trial ,Disease Progression ,Female ,Multiple Myeloma ,Autologous ,Boron Compounds ,Oral ,medicine.medical_specialty ,Glycine ,Multiple Myeloma/drug therapy ,BORTEZOMIB ,Antineoplastic Agents ,Placebo ,Research Support ,Transplantation, Autologous ,03 medical and health sciences ,Phase III ,Double-Blind Method ,Internal medicine ,medicine ,Journal Article ,Humans ,THALIDOMIDE ,Transplantation ,business.industry ,Clinical trial ,LENALIDOMIDE MAINTENANCE ,Regimen ,chemistry ,autologous stem cell transplantation, multiple myeloma, Ixazomib ,business ,HIGH-DOSE THERAPY ,Glycine/administration & dosage ,Stem Cell Transplantation - Abstract
[Background]: Maintenance therapy following autologous stem cell transplantation (ASCT) can delay disease progression and prolong survival in patients with multiple myeloma. Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile. In this study, we aimed to determine the safety and efficacy of ixazomib as maintenance therapy following ASCT. [Methods]: The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study took place in 167 clinical or hospital sites in 30 countries in Europe, the Middle East, Africa, Asia, and North and South America. Eligible participants were adults with a confirmed diagnosis of symptomatic multiple myeloma according to International Myeloma Working Group criteria who had achieved at least a partial response after undergoing standard-of-care induction therapy followed by high-dose melphalan (200 mg/m²) conditioning and single ASCT within 12 months of diagnosis. Patients were randomly assigned in a 3:2 ratio to oral ixazomib or matching placebo on days 1, 8, and 15 in 28-day cycles for 2 years following induction, high-dose therapy, and transplantation. The initial 3 mg dose was increased to 4 mg from cycle 5 if tolerated during cycles 1–4. Randomisation was stratified by induction regimen, pre-induction disease stage, and response post-transplantation. The primary endpoint was progression-free survival (PFS) by intention-to-treat analysis. Safety was assessed in all patients who received at least one dose of ixazomib or placebo, according to treatment actually received. This trial is registered with ClinicalTrials.gov, number NCT02181413, and follow-up is ongoing. [Findings]: Between July 31, 2014, and March 14, 2016, 656 patients were enrolled and randomly assigned to receive ixazomib maintenance therapy (n=395) or placebo (n=261). With a median follow-up of 31 months (IQR 27·3–35·7), we observed a 28% reduction in the risk of progression or death with ixazomib versus placebo (median PFS 26·5 months [95% CI 23·7–33·8] vs 21·3 months [18·0–24·7]; hazard ratio 0·72, 95% CI 0·58–0·89; p=0·0023). No increase in second malignancies was noted with ixazomib therapy (12 [3%] patients) compared with placebo (eight [3%] patients) at the time of this analysis. 108 (27%) of 394 patients in the ixazomib group and 51 (20%) of 259 patients in the placebo group experienced serious adverse events. During the treatment period, one patient died in the ixazomib group and none died in the placebo group. [Interpretation]: Ixazomib maintenance prolongs PFS and represents an additional option for post-transplant maintenance therapy in patients with newly diagnosed multiple myeloma, This study was sponsored by Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company.
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- 2019
22. Overcoming the unmet need of Richter transformation: the use of pirtobrutinib.
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Tadmor T
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- Humans, Adenine analogs & derivatives, Adenine therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Piperidines therapeutic use, Pyrazoles therapeutic use
- Abstract
Competing Interests: I declare no competing interests.
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- 2024
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23. Vitamin D supplement for patients with early-stage chronic lymphocytic leukemia is associated with a longer time to first treatment.
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Tadmor T, Melamed G, Alapi H, Gazit S, Patalon T, and Rokach L
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- Humans, Male, Female, Aged, Middle Aged, Retrospective Studies, Time-to-Treatment, Adult, Neoplasm Staging, Aged, 80 and over, Treatment Outcome, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Vitamin D therapeutic use, Vitamin D administration & dosage, Dietary Supplements
- Abstract
Abstract: Low levels of vitamin D are associated with a shorter time to first treatment (TTFT) and inferior overall survival in patients with chronic lymphocytic leukemia (CLL). But whether vitamin D supplement affects the clinical course of patients with CLL, remains an open question. In this study, we aimed to retrospectively explore the clinical benefit of vitamin D supplement or one of its analogs, on TTFT and treatment-free survival (TFS) in a large cohort of patients with asymptomatic CLL, who were under watch-and-wait approach. Among the 3474 patients included in the study, 931 patients (26.8%) received either vitamin D supplement or its analog, for a minimum of 6 months. We found that vitamin D supplement was statistically significant for longer TTFT in the young cohort (age ≤65) and was associated with a longer TFS for all ages (P = .004). Among non-vitamin-D users, the median TFS was found to be 84 months, whereas among vitamin D supplement users the median TFS extended to 169 months. In conclusion, our long-term retrospective study demonstrates that the administration of vitamin D to patients with CLL in a watch-and-wait active surveillance is significantly associated with a longer TFS (in any age) and a longer TTFT among young patients (age ≤65). A prospective clinical trial is needed to validate results., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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24. It's time to change the standard of care for hairy cell leukemia?!
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Lavie G and Tadmor T
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- 2024
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25. Hairy cell leukemia variant and WHO classification correspondence Re: 5 th edition WHO classification haematolymphoid tumors: lymphoid neoplasms.
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Grever M, Andritsos L, Anghelina M, Arons E, Banerji V, Barrientos J, Bhat SA, Blachly J, Broccoli A, Call T, Dearden C, Dietrich S, Else M, Epperla N, Fagarasanu A, Falini B, Forconi F, Gozzetti A, Hampel P, Hermel DJ, Iyengar S, Johnston JB, Juliusson G, Kreitman RJ, Lauria F, Lozanski G, Oakes CC, Parikh SA, Park J, Quest G, Rai K, Ravandi F, Robak T, Rogers KA, Saven A, Seymour JF, Tadmor T, Tallman MS, Tam CS, Tiacci E, Troussard X, Wörmann B, Zent CS, Zenz T, and Zinzani PL
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- Humans, Leukemia, Hairy Cell pathology, Leukemia, Hairy Cell classification, Leukemia, Hairy Cell diagnosis, World Health Organization
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- 2024
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26. Clinical and Economic Implications of Hydroxyurea Intolerance in Polycythemia Vera in Routine Clinical Practice.
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Ellis MH, Tadmor T, Yekutiel N, Chodick G, Levy M, Sharf G, Ben Zvi N, Leef R, Feine O, and Shavit O
- Abstract
Background/Objectives: Polycythemia vera (PV) is a chronic hematologic neoplasm commonly treated with hydroxyurea (HU). We utilized the advanced digitalized database of Maccabi Healthcare Services to retrospectively investigate the clinical and economic implications of HU intolerance in the routine clinical care of PV patients in Israel. Methods: We collected data on demographics, physician visits, hospitalizations, laboratory results, medication purchases, cardiovascular and thrombotic events, mental health, economic outcomes, and mortality. Outcomes included cardiovascular and other thrombotic events, disease progression, mental health events, economic outcomes, and overall mortality. Results: Of the 830 patients studied, 3 (0.4%) were resistant to HU treatment, 318 (38.3%) were intolerant to HU treatment, and 509 (61.3%) were stable on HU treatment. The venous thrombosis rate was significantly higher among HU-intolerant compared to HU-stable patients (1.58 vs. 0.47 per 100 person-years [PY], respectively; p < 0.001). The rate of progression to myelofibrosis was 6 vs. 0.9 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively ( p < 0.001), and the rate of progression to acute myeloid leukemia (AML) was 1.16 vs. 0.2 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively ( p < 0.001). The phlebotomy requirement, mortality rate, and total hospitalization days among HU-intolerant patients were significantly higher than in HU-stable patients ( p = 0.049, p < 0.001, p < 0.001, respectively). More mental health-related events were noted in HU-intolerant patients vs. HU-stable patients ( p = 0.007), and the total healthcare cost ratio was 2.65 for the HU-intolerant patients compared with HU-stable patients. Conclusions: This study suggests that HU-intolerant patients are more likely to have worse outcomes than HU-stable patients, highlighting the need for the close monitoring of these patients for disease-related complications or progression.
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- 2024
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27. Placental and serum levels of human α-Klotho in preeclampsia & intra-uterine growth retardation: A potential sensitive biomarker?
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Sabren S, Hagar T, Khateeb N, Evgeny F, Yara FN, Perlitz Y, and Farid N
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- Humans, Female, Pregnancy, Adult, Case-Control Studies, Glucuronidase blood, Glucuronidase genetics, Pre-Eclampsia blood, Fetal Growth Retardation blood, Klotho Proteins, Placenta metabolism, Biomarkers blood
- Abstract
Introduction: α-Klotho protein has three isoforms: a transmembrane (mKL), a shed- soluble isoform, and a circulating soluble isoform (sKL). mKL is expressed in the kidney and placenta, while sKL is detectable in blood and urine. It is known that α-Klotho levels fluctuate during pregnancy mainly in women with complications such as preeclampsia (PE) and intra-uterine growth restriction (IUGR)., Methods: Forty-nine participants were divided into two groups: healthy and complicated pregnancy (PE, IUGR or both). Tissue samples (2 cm3) from the maternal side, Blood and urine samples were collected during pregnancy and postpartum. Samples were subjected to biochemical (WB), histological (H&E and IHC) staining as well as genetic analysis (qPCR)., Results: Blood αKL levels were preserved in both healthy and complicated pregnancies. Significantly lower blood αKL concentrations were found in PE postpartum (PP) compared to levels during pregnancy, and were significantly lower compared with postpartum of a healthy pregnancy. αKL activity was reduced in complicated pregnancies vs. healthy pregnancies. Placen tal mKL levels (ELISA) and expression (WB) were lowered in complicated pregnancies compared with the healthy pregnancies group. Additionally, we found a significant decline in the expression of mKL mRNA in PE/IUGR placentas compared with the healthy group., Discussion: Several studies have focused on the involvement of αKL in normal placentation during pregnancy. Our results suggest lower function of sKL in complicated pregnancy compared with a control, and present differences in placental mKL levels as well as tissue and gene expression between healthy and complicated pregnancy. In light of our results, we conclude that complicated pregnancy is associated with in decline in mKL., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nakhoul Farid M.D reports was provided by The Galilee medical center Nahariya Israel., (Copyright © 2024 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)
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- 2024
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28. First-line venetoclax combinations versus chemoimmunotherapy in fit patients with chronic lymphocytic leukaemia (GAIA/CLL13): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial.
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Fürstenau M, Kater AP, Robrecht S, von Tresckow J, Zhang C, Gregor M, Thornton P, Staber PB, Tadmor T, Lindström V, Juliusson G, Janssens A, Levin MD, da Cunha-Bang C, Schneider C, Goldschmidt N, Vandenberghe E, Rossi D, Benz R, Nösslinger T, Heintel D, Poulsen CB, Christiansen I, Frederiksen H, Enggaard L, Posthuma EFM, Issa DE, Visser HPJ, Bellido M, Kutsch N, Dürig J, Stehle A, Vöhringer M, Böttcher S, Schulte C, Simon F, Fink AM, Fischer K, Holmes EE, Kreuzer KA, Ritgen M, Brüggemann M, Tausch E, Stilgenbauer S, Hallek M, Niemann CU, and Eichhorst B
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Follow-Up Studies, Rituximab administration & dosage, Rituximab adverse effects, Adenine analogs & derivatives, Adenine administration & dosage, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Progression-Free Survival, Cyclophosphamide administration & dosage, Pyrazoles administration & dosage, Pyrimidines administration & dosage, Immunotherapy, Adult, Bridged Bicyclo Compounds, Heterocyclic administration & dosage, Sulfonamides administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Piperidines administration & dosage, Vidarabine analogs & derivatives, Vidarabine administration & dosage
- Abstract
Background: In the primary analysis report of the GAIA/CLL13 trial, we found that venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib improved undetectable measurable residual disease (MRD) rates and progression-free survival compared with chemoimmunotherapy in patients with previously untreated chronic lymphocytic leukaemia. However, to our knowledge, no data on direct comparisons of different venetoclax-based combinations are available., Methods: GAIA/CLL13 is an open-label, randomised, phase 3 study conducted at 159 sites in ten countries in Europe and the Middle East. Eligible patients were aged 18 years or older, with a life expectancy of at least 6 months, an Eastern Cooperative Oncology group performance status of 0-2, a cumulative illness rating scale score of 6 or lower or a single score of 4 or lower, and no TP53 aberrations. Patients were randomly assigned (1:1:1:1), with a computer-generated list stratified by age, Binet stage, and regional study group, to either chemoimmunotherapy, venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. All treatments were administered in 28-day cycles. Patients in the chemoimmunotherapy group received six cycles of treatment, with patients older than 65 years receiving intravenous bendamustine (90 mg/m
2 , days 1-2), whereas patients aged 65 years or younger received intravenous fludarabine (25 mg/m2 , days 1-3) and intravenous cyclophosphamide (250 mg/m2 , days 1-3). Intravenous rituximab (375 mg/m2 , day 1 of cycle 1; 500 mg/m2 , day 1 of cycles 2-6) was added to chemotherapy. In the experimental groups, patients received daily venetoclax (400 mg orally) for ten cycles after a 5-week ramp-up phase starting on day 22 of cycle 1. In the venetoclax-rituximab group, intravenous rituximab (375 mg/m2 , day 1 of cycle 1; 500 mg/m2 , day 1 of cycles 2-6) was added. In the obinutuzumab-containing groups, obinutuzumab was added (cycle 1: 100 mg on day 1, 900 mg on day 2, and 1000 mg on days 8 and 15; cycles 2-6: 1000 mg on day 1). In the venetoclax-obinutuzumab-ibrutinib group, daily ibrutinib (420 mg orally, from day 1 of cycle 1) was added until undetectable MRD was reached in two consecutive measurements (3 months apart) or until cycle 36. The planned treatment duration was six cycles in the chemoimmunotherapy group, 12 cycles in the venetoclax-rituximab and the venetoclax-obinutuzumab group and between 12 and 36 cycles in the venetoclax-obinutuzumab-ibrutinib group. Coprimary endpoints were the undetectable MRD rate in peripheral blood at month 15 for the comparison of venetoclax-obinutuzumab versus standard chemoimmunotherapy and investigator-assessed progression-free survival for the comparison of venetoclax-obinutuzumab-ibrutinib versus standard chemoimmunotherapy, both analysed in the intention-to-treat population (ie, all patients randomly assigned to treatment) with a split α of 0·025 for each coprimary endpoint. Both coprimary endpoints have been reported elsewhere. Here we report a post-hoc exploratory analysis of updated progression-free survival results after a 4-year follow-up of our study population. Safety analyses included all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT02950051, recruitment is complete, and all patients are off study treatment., Findings: Between Dec 13, 2016, and Oct 13, 2019, 1080 patients were screened and 926 were randomly assigned to treatment (chemoimmunotherapy group n=229; venetoclax-rituximab group n=237; venetoclax-obinutuzumab group n=229; and venetoclax-obinutuzumab-ibrutinib group n=231); mean age 60·8 years (SD 10·2), 259 (28%) of 926 patients were female, and 667 (72%) were male (data on race and ethnicity are not reported). At data cutoff for this exploratory follow-up analysis (Jan 31, 2023; median follow-up 50·7 months [IQR 44·6-57·9]), patients in the venetoclax-obinutuzumab group had significantly longer progression-free survival than those in the chemoimmunotherapy group (hazard ratio [HR] 0·47 [97·5% CI 0·32-0·69], p<0·0001) and the venetoclax-rituximab group (0·57 [0·38-0·84], p=0·0011). The venetoclax-obinutuzumab-ibrutinib group also had a significantly longer progression-free survival than the chemoimmunotherapy group (0·30 [0·19-0·47]; p<0·0001) and the venetoclax-rituximab group (0·38 [0·24-0·59]; p<0·0001). There was no difference in progression-free survival between the venetoclax-obinutuzumab-ibrutinib and venetoclax-obinutuzumab groups (0·63 [0·39-1·02]; p=0·031), and the proportional hazards assumption was not met for the comparison between the venetoclax-rituximab group versus the chemoimmunotherapy group (log-rank p=0·10). The estimated 4-year progression-free survival rate was 85·5% (97·5% CI 79·9-91·1; 37 [16%] events) in the venetoclax-obinutuzumab-ibrutinib group, 81·8% (75·8-87·8; 55 [24%] events) in the venetoclax-obinutuzumab group, 70·1% (63·0-77·3; 84 [35%] events) in the venetoclax-rituximab group, and 62·0% (54·4-69·7; 90 [39%] events) in the chemoimmunotherapy group. The most common grade 3 or worse treatment-related adverse event was neutropenia (114 [53%] of 216 patients in the chemoimmunotherapy group, 109 [46%] of 237 in the venetoclax-rituximab group, 127 [56%] of 228 in the venetoclax-obinutuzumab group, and 112 [48%] of 231 in the venetoclax-obinutuzumab-ibrutinib group). Deaths determined to be associated with study treatment by the investigator occurred in three (1%) patients in the chemoimmunotherapy group (n=1 due to each of sepsis, metastatic squamous cell carcinoma, and Richter's syndrome), none in the venetoclax-rituximab and venetoclax-obinutuzumab groups, and four (2%) in the venetoclax-obinutuzumab-ibrutinib group (n=1 due to each of acute myeloid leukaemia, fungal encephalitis, small-cell lung cancer, and toxic leukoencephalopathy)., Interpretation: With more than 4 years of follow-up, venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib significantly extended progression-free survival compared with both chemoimmunotherapy and venetoclax-rituximab in previously untreated, fit patients with chronic lymphocytic leukaemia, thereby supporting their use and further evaluation in this patient group, while still considering the higher toxicities observed with the triple combination., Funding: AbbVie, Janssen, and F Hoffmann-La Roche., Competing Interests: Declaration of interests MF reports research funding from AbbVie, AstraZeneca, BeiGene, Janssen, and Roche, and honoraria from AbbVie. JvT reports honoraria from AbbVie, BeiGene, Amgen, AstraZeneca, Janssen, Lilly, and Roche; travel grants from AbbVie, AstraZeneca, BeiGene, Roche, Lilly, and Janssen; and has received consulting fees from and participated on advisory boards for AbbVe, BeiGene, Amgen, and AstraZeneca. MG has received honoraria for participation in symposia and advisory boards from AbbVie, Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb (BMS)/Celgene, GSK, Novartis, Incyte, Janssen-Cilag, Jazz, Roche, Pfizer, Sanofi, and Servier; travel support from AbbVie, BeiGene, Pfizer, and Roche; all fees went to their institution. GJ has received honoraria from Astellas and AbbVie and participated on advisory boards for AbbVie and Servier. M-DL reports travel grants from AbbVie and Janssen. CdC-B reports consulting fees from Janssen, honoraria for lectures from Octapharma, support for attending meetings from AbbVie and Octapharma, and participation on advisory boards for Janssen, BeiGene, and AstraZeneca. CSchn reports speakers fees from AstraZeneca and AbbVie, travel support from AbbVie, and participation on an advisory board for Janssen. RB reports travel support from BeiGene, Janssen, and AbbVie, and honoraria for participation on an advisory board from AbbVie. TN reports honoraria for lectures or presentations and has participated at advisory boards from AbbVie, Roche, AstraZeneca, Gilead, BeiGene, and Janssen. CBP is the chairman of the Danish CLL group. HF reports research funding from Sanofi, Novartis, and Alexion and honoraria for lectures from Sanofi. NK reports research funding from AstraZeneca; honoraria from AbbVie, AstraZeneca, Kite/Gilead, BMS, and Lilly; and travel support from AbbVie, AstraZeneca, BeiGene, Lilly, and Janssen; and participation on advisory boards for AstraZeneca and Janssen. JD reports consulting fees, honoraria, and travel support from AbbVie and Janssen. SB reports honoraria from and participation on speakers bureaus for Roche, Janssen, AbbVie, AstraZeneca, and Sanofi; travel support from Janssen, BeiGene, and Roche; and research funding from Janssen and Miltenyi. FS reports speakers fees from AstraZeneca, travel support from Lilly, and research funding from AstraZeneca. A-MF reports research funding and honoraria from AstraZeneca and travel support from AbbVie. KF reports research grants from AbbVie and Roche, honoraria for advisory boards from AstraZeneca, and travel support from Roche. K-AK reports consulting fees, participation on speakers bureaus, and research funding from Roche, AbbVie, and Janssen. MR reports honoraria from Janssen, Roche, and AstraZeneca; consulting fees from Roche, Janssen, AstraZeneca, and AbbVie; research funding from AbbVie and Roche, and travel support from AstraZeneca. MBr reports research funding and consulting fees from Amgen; honoraria for speakers bureaus from Amgen, Becton Dickinson, Janssen, and Pfizer; travel support from Janssen; and participation on advisory boards for Incyte and Amgen. ET reports participation on advisory boards and honoraria from AbbVie, Janssen-Cilag, and BeiGene, AstraZeneca, and Roche; and travel support from AstraZeneca, AbbVie, BeiGene, Janssen. SS reports honoraria from AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann-La Roche, Janssen, Novartis, and Sunesis; research funding from AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann-La Roche, Janssen, Novartis, and Sunesis; travel support from AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann-La Roche, Janssen, Novartis, Sunesis; and speaker fees from AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann-La Roche, Janssen, Novartis, and Sunesis. MH reports consulting fees from Roche, Gilead, Janssen, BMS, AbbVie, and AstraZeneca and honoraria from Roche, Gilead, Janssen, BMS, AbbVie, and AstraZeneca. APK reports honoraria from AbbVie, AstraZeneca, BMS, Janssen, LAVA, and Roche/Genentech; travel grants from AbbVie and Janssen; research funding from AstraZeneca, Janssen, Roche/Genentech, AbbVie, and BMS. CUN reports research funding from Octapharma and AstraZeneca; consultancy and speaker fees from AbbVie, AstraZeneca, Janssen, Genmab, BeiGene, Octapharma, CSL Behring, Takeda, Lilly, and MSD; and participation on advisory boards for AstraZeneca, MSD, Genmab, and Janssen. BE reports consulting fees fromJanssen, AbbVie, Gilead, AstraZeneca, MSD, BeiGene, and Lilly; participation on speakers bureau for Roche, AbbVie, BeiGene, AstraZeneca, and MSD; honoraria from Roche, AbbVie, AstraZeneca, BeiGene, and MSD; research funding from Janssen, Gilead, Roche, AbbVie, BeiGene, and AstraZeneca; and travel support from BeiGene. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
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29. Improved Survival of Patients With Chronic Lymphocytic Leukemia Between 1998-2022, Including the Era of Target Therapies With BCL2 and BTK Inhibitors.
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Tadmor T, Melamed G, Alapi H, Gazit S, Patalon T, and Rokach L
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- Female, Humans, Male, Israel epidemiology, Molecular Targeted Therapy, Retrospective Studies, Agammaglobulinaemia Tyrosine Kinase antagonists & inhibitors, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Protein Kinase Inhibitors therapeutic use, Proto-Oncogene Proteins c-bcl-2 antagonists & inhibitors
- Abstract
Background/aim: The treatment for chronic lymphocytic leukemia (CLL) has changed dramatically over the last two decades. The current study aimed to investigate the impact on overall survival (OS) and time to next treatment (TTT) among CLL patients from 1998 to 2022., Patients and Methods: The cohort was based on data obtained from electronic medical records of Maccabi, the second largest healthcare organization in Israel. All included patients were diagnosed with CLL based on the IWCLL criteria and complete clinical, laboratory, and treatment data were available. The study encompassed 3,964 patients diagnosed with CLL during the specified study period., Results: Patients with CLL who required therapy were divided into three eras based on the dominant treatment approach: chemotherapy alone before 2010, therapy with chemotherapy and anti-CD20 between 2010 and 2017, and therapy with targeted agents between 2017 and 2022. Median OS was 4.1 years, 7.5 years, and not reached, respectively. The six-year OS rates were 40%, 55%, and 69%, respectively, (p=0.0001). The median time to the next treatment improved from 5.5 years before 2010, to 8.3 between 2010-2017, to not reached after 2017 (p=0.0021)., Conclusion: Marked improvements in survival subsequent to fundamental changes in first-line therapy were found in patients with CLL from before 2010 to after 2017., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2024
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30. Therapy with mosunetuzumab, a bispecific antibody for relapsed/refractory hairy cell leukemia.
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Tadmor T and Levy Yurkovski I
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- Humans, Middle Aged, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Agents, Immunological therapeutic use, Drug Resistance, Neoplasm, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology, Recurrence, Treatment Outcome, Female, Antibodies, Bispecific therapeutic use, Leukemia, Hairy Cell drug therapy
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- 2024
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31. Efficacy of preexposure prophylaxis with monoclonal-antibody tixagevimab-cilgavimab against emerging SARS-CoV-2 resistant variants in patients with chronic lymphocytic leukemia.
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Benjamini O, Tadmor T, Avigdor A, Gershon R, Kliker L, Fares F, Atari N, Laevsky I, Abd Elkader B, Hod T, Golan-Shany O, Mandelboim M, and Rahav G
- Abstract
Introduction Pre exposure prophylaxis with monoclonal antibodies (mAbs) were developed in addition to COVID19 vaccine for immunocompromised and those with insufficient immune response, among them patients with CLL. Omicron variant and its sublineages evolved mutations that escape mAbs neutralizing effect, yet the extent of which was not studied. Methods We evaluated anti-spike titters and neutralization activity of COVID-19 wild type (WT) , Delta , Omicron, BA2, BA4 and BA5 before and after tixagevimab-cilgavimab (TGM/CGM) dose of 150/150mg or 300/300mg in patients with CLL. Results 70 patients were tested 2 weeks before and 4 weeks after receiving TGM/CGM mAbs. After TGM/CGM anti-spike ab level increased 170 folds from 13.6 BAU/ml (IQR, 0.4-288) to 2328 BAU/ml (IQR, 1681-3500). Neutralization activity increased in all variants, and was 176 folds higher in WT and 55 folds higher in Delta compared to 10 folds higher in Omicron and its sublineages (BA2 x11, BA4 x4 , BA5 x18). Over follow-up period of 3 months, 20 patients (29%) with CLL acquired COVID-19 infection, all recovered uneventfully. In a multivariate analysis anti-spike antibody titer was found a significant predictor for post TGM/CGM COVID19 infection. Conclusion Efficacy of preexposure prophylaxis with TGM/CGM in patients with CLL is significantly reduced in era of Omicron and its sublineages BA2, BA4 and BA5., (The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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32. Accelerated Chronic Lymphocytic Leukemia and Richter Transformation in the Era of Novel Agents.
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Levy Yurkovski I and Tadmor T
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- Humans, B-Lymphocytes, Prognosis, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
Background: Tremendous developments in the field of chronic lymphocytic leukemia (CLL) in recent years have led to a revolutionary change in the treatment approach, which today is based on targeted treatments with a good response and optimal prognosis. Nevertheless, CLL can present or progress to "accelerated CLL" (A-CLL) or to "Richter transformation" (RT) and these two entities have a more aggressive course and are still characterized by challenges in the fields of diagnosis and therapy. In the current review, we summarized the latest knowledge in terms of diagnostic approaches to A-CLL, available treatments and clinical trials, for both A-CLL and RT which still pose an unmet need and require additional basic and clinical investigations., Summary: A-CLL is a rare and underdiagnosed entity that probably stands in the "gray zone" between CLL and RT, generally holding an intermediate prognosis. Its diagnosis is mainly based on histological findings including expanded proliferation centers, increased mitotic activity, and/or high Ki-67 index. Due to its rarity, its treatment approach has still not been defined, but it seems that novel agents, especially Bruton tyrosine kinase inhibitors (BTKi), are effective. As for RT, the standard therapy still consists of chemo-immunotherapy followed by stem-cell transplantation for fit responders with a dismal prognosis. New approaches are recently adopted including B-cell inhibition via novel agents (BTKi, venetoclax), T-cell engagers (checkpoint inhibitors, bispecific antibodies [BiTe] or the chimeric antigen receptor [CAR] technology), antibody-drug conjugates, or drug combinations. Although both CAR-T and BiTe seem promising, especially when combined with BTKi, evidence is still insufficient, and patients should generally be recruited in clinical trials., Key Messages: The field of CLL has been a subject of major advances in recent years, but A-CLL and RT remain topics of "unmet need" and require further studies to identify the best diagnostic approach and a more effective treatment., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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33. Chronic Lymphocytic Leukemia: Novel Perspectives - How to Teach an Old Dog New Tricks.
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Tadmor T and Burger J
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- Humans, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
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- 2024
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34. The Involvement of LAG-3 positive Plasma Cells in the Development of Multiple Myeloma.
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Kreiniz N, Eiza N, Tadmor T, Levy Yurkovski I, Matarasso Greenfeld S, Sabag A, Mubariki R, Suriu C, Votinov E, Toubi E, and Vadasz Z
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- Humans, Plasma Cells, Granzymes, Multiple Myeloma, Neoplasms, Plasma Cell, Paraproteinemias, Monoclonal Gammopathy of Undetermined Significance
- Abstract
The Lymphocyte-Activation Protein 3 (LAG-3) inhibitory receptor is expressed on regulatory plasma cells (PCs). Micro-environmental cells that express LAG-3 were found to be increased during the progression of smoldering multiple myeloma (SMM). To assess the possible role of LAG-3 expression on regulatory PCs in patients with plasma cell dyscrasia. Purified Cluster of Differentiation 138 (CD138
+) PCs from patients with premalignant conditions, active multiple myeloma (MM), and controls were analyzed for the expression of LAG-3 by flow cytometry. Autologous CD8+ T cells were incubated with sorted LAG-3pos or LAG-3neg PCs for 24 h. The expression of granzyme (Grz) in CD8+ T cells was assessed by flow cytometry. LAG-3 expression on PCs in active MM (newly diagnosed and relapse refractory MM) was significantly increased compared to monoclonal gammopathy of undetermined significance (MGUS)/ SMM. Grz expression was significantly decreased in CD8+ T cells incubated with CD138+ LAG-3pos PCs, compared to CD138+ LAG-3neg PCs in patients with plasma cell dyscrasia, n = 31, p = 0.0041. LAG-3 expression on malignant PCs can be involved in the development of MM from MGUS by decreasing the expression of Grz in CD8+ T cells.- Published
- 2023
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35. Integrative Approaches in the Treatment of Patients Affected by Lymphoma.
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Levy Yurkovski I, Andreazzoli F, Ben-Arye E, Attias S, and Tadmor T
- Subjects
- Humans, Diet, Nausea, Complementary Therapies, Acupuncture Therapy, Lymphoma therapy, Integrative Medicine
- Abstract
Purpose of Review: Lymphoma is the most frequent hematological malignancy with wide disease spectrum of watchful waiting period, active treatment, survivorship, and palliative care. All these steps impose unmet needs in terms of prevention, symptom alleviation, or prognosis. Complementary and integrative medicine (CIM) is widely used by patients with lymphoma to cope with such issues. Here, we describe the different CIM modalities that may be effective and safe for the management of patients with lymphoma., Recent Findings: Low inflammatory diet and ginseng seem effective for lymphoma prevention. Pain and neuropathy may be improved using acupuncture, touch therapy and specific dietary supplements. Nausea/vomiting, fatigue, and insomnia may be relieved by acupuncture, mind-body, touch therapy, and certain dietary supplements. Vitamin D, curcumin, and some traditional medicine herbs may positively impact lymphoma prognosis. Finally, safety issues should be considered especially for the concomitant use of dietary supplements and lymphoma-directed therapies. CIM may be beneficial along the continuum of lymphoma management although safety concerns should be considered when used concomitantly with conventional therapy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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36. The course of patients with hairy cell leukemia during the omicron surge of the Covid-19 pandemic.
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Tadmor T, Melamed G, Patalon T, Alapi H, and Rokach L
- Subjects
- Humans, Aged, BNT162 Vaccine, Pandemics, COVID-19 epidemiology, Leukemia, Hairy Cell epidemiology, Cardiovascular Diseases
- Abstract
In this study, we aim to explore the outcomes of Covid-19 infection in patients with Hairy cell leukemia (HCL). The cohort is based on data obtained from electronic medical records. It includes 218 consecutive patients diagnosed with HCL between 16 June 1998, and 20 September 2022, out of which the coronavirus has infected 85 patients during the Omicron surge. Out of 85 patients with HCL who were infected by Covid-19; 7 patients (8.2%) have been hospitalized, and the mortality rate was 2.3% (two patients). Thirteen of the 85 patients had been infected by Covid-19 in previous waves, including 9/13 after vaccination, and none of them developed a severe disease. Humoral immune response after three doses of the BNT162b2 mRNA vaccination regimen was evaluated in 40 patients and was attained in 67.5%. Based on multivariate analysis: unfavorable outcome was significantly more common in patients with HCL above 65 years old, who had at least one cytopenia, and with comorbidity of cardiovascular disease or asplenia. Our results indicates that the course of COVID-19 in patients with HCL during the Omicron wave has been improved relatively favorable., (© 2023 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)
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- 2023
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37. The evolving landscape of COVID-19 and post-COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL.
- Author
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Visentin A, Chatzikonstantinou T, Scarfò L, Kapetanakis A, Demosthenous C, Karakatsoulis G, Minga E, Chamou D, Allsup D, Cabrero AA, Andres M, Antic D, Baile M, Baliakas P, Besikli-Dimou S, Bron D, Chatzileontiadou S, Cordoba R, Correa JG, Cuéllar-García C, De Paoli L, De Paolis MR, Delgado J, Dimou M, Donaldson D, Catherwood M, Doubek M, Efstathopoulou M, Eichhorst B, Elashwah S, Enrico A, Espinet B, Farina L, Ferrari A, Foglietta M, Frederiksen H, Fürstenau M, García-Marco JA, García-Serra R, Collado R, Gentile M, Gimeno E, Glenthøj A, da Silva MG, Hakobyan YK, Herishanu Y, Hernández-Rivas JÁ, Herold T, Innocenti I, Itchaki G, Jaksic O, Janssens A, Kalashnikova ОB, Kalicińska E, Kater AP, Kersting S, Labrador J, Lad D, Laurenti L, Levin MD, Lista E, Lopez-Garcia A, Malerba L, Marasca R, Marchetti M, Marquet J, Mattsson M, Mauro FR, Morawska M, Motta M, Munir T, Murru R, Niemann CU, Rodrigues RN, Olivieri J, Orsucci L, Papaioannou M, Pavlovsky MA, Piskunova I, Popov VM, Quaglia FM, Quaresmini G, Qvist K, Rigolin GM, Ruchlemer R, Šimkovič M, Špaček M, Sportoletti P, Stanca O, Tadmor T, Capasso A, Del Poeta G, Gutwein O, Karlsson LK, Milosevic I, Mirás F, Reda G, Saghumyan G, Shrestha A, Te Raa D, Tonino SH, Van Der Spek E, van Gelder M, van Kampen R, Wasik-Szczepanek E, Wróbel T, Segundo LYS, Yassin M, Pocali B, Vandenberghe E, Iyengar S, Varettoni M, Vitale C, Coscia M, Rambaldi A, Montserrat E, Cuneo A, Stavroyianni N, Trentin L, Stamatopoulos K, and Ghia P
- Subjects
- Humans, SARS-CoV-2, Post-Acute COVID-19 Syndrome, Retrospective Studies, COVID-19, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Abstract
In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
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- 2023
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38. Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY.
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Chatzikonstantinou T, Scarfò L, Karakatsoulis G, Minga E, Chamou D, Iacoboni G, Kotaskova J, Demosthenous C, Smolej L, Mulligan S, Alcoceba M, Al-Shemari S, Aurran-Schleinitz T, Bacchiarri F, Bellido M, Bijou F, Calleja A, Medina A, Khan MA, Cassin R, Chatzileontiadou S, Collado R, Christian A, Davis Z, Dimou M, Donaldson D, Santos GD, Dreta B, Efstathopoulou M, El-Ashwah S, Enrico A, Fresa A, Galimberti S, Galitzia A, García-Serra R, Gimeno E, González-Gascón-Y-Marín I, Gozzetti A, Guarente V, Guieze R, Gogia A, Gupta R, Harrop S, Hatzimichael E, Herishanu Y, Hernández-Rivas JÁ, Inchiappa L, Jaksic O, Janssen S, Kalicińska E, Laribi K, Karakus V, Kater AP, Kho B, Kislova M, Konstantinou E, Koren-Michowitz M, Kotsianidis I, Kreitman RJ, Labrador J, Lad D, Levin MD, Levy I, Longval T, Lopez-Garcia A, Marquet J, Martin-Rodríguez L, Maynadié M, Maslejova S, Mayor-Bastida C, Mihaljevic B, Milosevic I, Miras F, Moia R, Morawska M, Murru R, Nath UK, Navarro-Bailón A, Oliveira AC, Olivieri J, Oscier D, Panovska-Stavridis I, Papaioannou M, Papajík T, Kubova Z, Phumphukhieo P, Pierie C, Puiggros A, Rani L, Reda G, Rigolin GM, Ruchlemer R, Daniel de Deus Santos M, Schipani M, Schiwitza A, Shen Y, Simkovic M, Smirnova S, Abdelrahman Soliman DS, Spacek M, Tadmor T, Tomic K, Tse E, Vassilakopoulos T, Visentin A, Vitale C, von Tresckow J, Vrachiolias G, Vukovic V, Walewska R, Wasik-Szczepanek E, Xu Z, Yagci M, Yañez L, Yassin M, Zuchnicka J, Angelopoulou M, Antic D, Biderman B, Catherwood M, Claus R, Coscia M, Cuneo A, Demirkan F, Espinet B, Gaidano G, Kalashnikova OB, Laurenti L, Nikitin E, Pangalis GA, Panagiotidis P, Popov VM, Pospisilova S, Sportoletti P, Stavroyianni N, Tam C, Trentin L, Chatzidimitriou A, Bosch F, Doubek M, Ghia P, and Stamatopoulos K
- Abstract
Background: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work., Methods: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022., Findings: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79-4.91; p < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49-2.11; p < 0.001/OR = 1.89; 95% CI = 1.6-2.24; p < 0.001).CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36-2.41; p < 0.001/OR = 2.11; 95% CI = 1.12-3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08-0.33; p < 0.001).Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001)., Interpretation: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS., Funding: AbbVie, and EU/EFPIAInnovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026., Competing Interests: TC received honoraria from AbbVie. LS received consulting fees from AbbVie, BeiGene, AstraZeneca, Lilly, and Janssen, honoraria from Janssen and Octapharma, support for attending meetings from BeiGene and Janssen and advisory board fees from Merck. SMu received advisory board fees from AbbVie, AstraZeneca, Janssen, Roche and BeiGene. JAHR received honoraria as a consultant from Janssen, AbbVie, AstraZeneca, Lilly, and BeiGene and support for attending meetings from Janssen, AbbVie, AstraZeneca, and BeiGene. LI received honoraria from AbbVie, Roche, and Janssen-Cilag. APK received advisory board fees and research money from Janssen, AbbVie, BMS, AstraZeneca, Roche/Genentech, support for attending meetings from Janssen and AbbVie. M-DL received travel expenses from Janssen and AbbVie. GMR received honoraria for participation to speaker's bureau from AbbVie, Astra Zeneca, Beigene, and Janssen, and support for attending meetings from Janssen. JVT received consulting fees from AbbVie, AstraZeneca, BeiGene, and Janssen, honoraria for scientific talks from AbbVie, AstraZeneca, BeiGene, Janssen, Lilly, and Roche, travel support from AbbVie, AstraZeneca, BeiGene, Janssen, Roche, and Lilly, and advisory boards fees for AbbVie, Amgen, AstraZeneca, BeiGene. GI received honoraria from Novartis, BMS, Sandoz, AstraZeneca, Janssen, Kite/Gilead, and Miltenyi, support for attending meetings from Kite/Gilead, AstraZeneca, and AbbVie and advisory board fees from Kite/Gilead, Novartis, BMS, and Autolus. FBi received support for attending meetings from AbbVie. RCo received support for attending meetings from Janssen-Cilag and S.A. SG received honoraria support for attending meetings from AbbVie, AstraZeneca, Jazz, Novartis, and Incyte, honoraria from Roche, Celgene, Pfizer, and Janssen, and support for attending meetings from Jazz, AstraZeneca, and Roche. RGS received support for attending meetings from AbbVie and S.L.U. RG received honoraria, consulting fees, and support for attending meetings from AbbVie, Beigene, Roche, Janssen, AstraZeneca. YH received honoraria from Janssen, AbbVie, Roche, AstraZeneca, Medion, and Lilly. OJ received honoraria from Johnson and Johnson, AstraZeneca, and Lilly, honoraria from Johnson and Johnson, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Johnson and Johnson, and AbbVie. LK received consulting fees from AbbVie, AstraZeneca, Janssen, Beigene, Takeda, and Novartis. MKM received honoraria from Novartis, Pfizer, and Gad Medical LTD and support for attending meetings from Novartis. IKo received honoraria and consulting fees from AbbVie and Janssen. IM received honoraria from AbbVie, Roche, Sandoz, AstraZeneca, and Janssen, and support for attending meetings from AbbVie, Roche, and Takeda. ANB received honoraria, advisory board fees and support for attending meetings from AbbVie, AstraZeneca, Takeda, Janssen, and Beigene. JO received honoraria from AbbVie, AstraZeneca, and Janssen. GR received consulting fees from AbbVie, AstraZeneca, Janssen, and Beigene, and is currently employed by AstraZeneca. TP received honoraria and advisory board fees from AbbVie, Janssen-Cilag, and AstraZeneca and support for attending meeting from AstraZeneca. MS received honoraria and support for attending meeting from AstraZeneca, AbbVie, and Janssen-Cilag and owns shares of stock in AbbVie, AstraZeneca, Merck, Eli Lilly, Sanofi, Johnson and Johnson, Pfizer, Gilead, and GSK. MSp received honoraria and consulting and advisory board fees, and support for attending meeting from AbbVie, AstraZeneca, and Janssen. ET received support for attending meetings from Takeda. TV received honoraria from Takeda, Roche, Genesis Pharma, Merck, Novartis, Gilead, Sandoz, AstraZeneca, Integris, and Servier and support for attending meetings from Takeda, Roche, Genesis Pharma, Merck, Pfizer, and Winmedica. CV received honoraria from AbbVie, consulting fees from AstraZeneca and support for attending meeting from AstraZeneca, Takeda, and Janssen. RW received honoraria from AbbVie, AstraZeneca, and Beigene, support for attending meetings from Janssen, AbbVie, and AstraZeneca and advisory board fees from AbbVie, AstraZeneca, Janssen, Beigene, and SecuraBio. EWS received honoraria from AbbVie, Roche, and Janssen-Cilag and support for attending meetings from AbbVie. LY received honoraria from AbbVie, AstraZeneca, Novartis, Gilead, Janssen, Jazz, MSD, and Pfizer, support for attending meetings from AbbVie, AstraZeneca, Gilead, Janssen, and Pfizer, and advisory board fees from AbbVie, AstraZeneca, Jazz, Janssen, Beigene, and Celgene. MAn received consulting fees from AbbVie, Takeda, Janssen, Roche, Genesis, Gilead, and Amgen and honoraria from AbbVie, Takeda, Roche, Genesis, Gilead, and Novartis. MC received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, and Janssen. ACu received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, Beigene, Janssen, and Lilly. FD support for attending meetings from Janssen and AbbVie. GG received honoraria, and advisory board fees from AbbVie, AstraZeneca, Beigene, Janssen and advisory board fees from Lilly. EN received honoraria from AbbVie. LSm received consulting fees, honoraria and support for attending meetings from AbbVie, AstraZeneca, and Janssen and advisory board fees from AbbVie and AstraZeneca. NS received honoraria from Janssen, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Janssen and AstraZeneca. CT received honoraria from AbbVie, Beigene, Janssen, and LOXO. FB received consulting fees, honoraria and payment for expert testimony from AbbVie, Genentech, Novartis, Takeda, Janssen, Roche, Mundipharma, Celgene/BMS, AstraZeneca, Lilly, Beigene, Gilead and TG Therapeutics, Advantage Allogene, Lava Therapeutics, and Enterome. MDo received honoraria and advisory board fees from AbbVie, AstraZeneca and Janssen, advisory board fees from Swixx, and support for attending meetings from Janssen. PG received honoraria and consulting fees from AbbVie, AstraZeneca, BMS, Janssen, Lilly/Loxo Oncology, MSD, and Roche; grant support from AbbVie, AstraZeneca, BMS, Janssen. KS received honoraria from Janssen, AbbVie, Lilly and AstraZeneca, consulting fees and support for attending meetings from Janssen and AstraZeneca. GK, EM, DC, JK, CD, MA, SA, TAS, FBa, MB, ACa, AM, AKM, RC, SC, ACh, ZD, MDi, DD, GDS, BD, ME, SEA, AE, AF, AG, EG, IGGM, AGo, AjG, RGu, SH, EH, SJ, EKa, VK, BK, MK, EK, RJK, JL, DL, IL, TL, ALG, JM, LMR, MMa, SM, CMB, BM, FM, RM, MMo, RMu, UKN, ACO, DO, IPS, MP, ZK, PP, CP, AP, LR, RR, MDDS, AS, YS, MSi, SS, DSAS, TT, KT, AV, GV, VV, ZX, MYa, MY, JZ, DA, BB, MCa, RCl, BE, OBK, LL, GP, PPa, VMP, SP, PS, LT, AC, have no conflict of interest to disclose., (© 2023 Published by Elsevier Ltd.)
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- 2023
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39. Timing of BNT162b2 vaccine prior to COVID-19 infection, influence disease severity in patients with hematologic malignancies: Results from a cohort study.
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Gutwein O, Herzog Tzarfati K, Apel A, Rahimi-Levene N, Ilana L, Tadmor T, and Koren-Michowitz M
- Subjects
- Humans, BNT162 Vaccine, Cohort Studies, Pandemics, Retrospective Studies, SARS-CoV-2, Patient Acuity, Antiviral Agents, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, COVID-19 prevention & control, Hematologic Neoplasms complications, Vaccines
- Abstract
The COVID-19 pandemic continues to pose challenges to the treatment of hemato-oncology patients. Emergence of COVID-19 variants, availability of vaccine boosters and antiviral treatments could impact their outcome. We retrospectively studied patients with hematologic malignancies and confirmed COVID-19 during the Omicron outbreak. Of 116 evaluated patients, 16% developed severe or critical COVID-19. Diagnosis of chronic lymphocytic leukemia (CLL) was significantly associated with severe COVID-19 (p = 0.01). The vaccine effectiveness was related to the timing of the vaccine, with patients who received a mRNA vaccine within 7-90 days prior to COVID-19 being less likely to develop severe disease compared to all other patients (p = 0.019). There was no correlation between disease severity and antiviral therapies. Importantly, 45% of patients undergoing active hematological treatment had to interrupt their treatment due to COVID-19. In conclusion, patients with hematologic malignancies are at a considerable risk for severe COVID-19 during the Omicron outbreak, with patients with CLL being the most vulnerable. mRNA vaccines have the potential to protect hematological patients from severe COVID-19 if administered within the previous 3 months. Hematological treatment interruption is a frequent adverse outcome of COVID-19 infection., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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40. High karyotypic complexity is an independent prognostic factor in patients with CLL treated with venetoclax combinations.
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Fürstenau M, Thus YJ, Robrecht S, Mellink CHM, van der Kevie-Kersemaekers AM, Dubois J, von Tresckow J, Patz M, Gregor M, Thornton P, Staber PB, Tadmor T, Levin MD, da Cunha-Bang C, Schneider C, Poulsen CB, Illmer T, Schöttker B, Janssens A, Christiansen I, Nösslinger T, Baumann M, Hebart H, Gaska T, Regelink JC, Dompeling EC, Lindström V, Juliusson G, Widmer A, Goede J, Goldschmidt N, Simon F, De Silva N, Fink AM, Fischer K, Wendtner CM, Ritgen M, Brüggemann M, Tausch E, Spaargaren M, Eldering E, Stilgenbauer S, Niemann CU, Hallek M, Eichhorst B, Kreuzer KA, and Kater AP
- Subjects
- Humans, Abnormal Karyotype, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Karyotype, Karyotyping, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell genetics
- Abstract
Complex karyotypes have been associated with inferior outcomes in chronic lymphocytic leukemia (CLL) treated with chemoimmunotherapy (CIT), whereas their prognostic impact in the context of venetoclax-based treatments is still debated. In this prospective analysis on karyotype complexity in CLL, we evaluated the impact of complex (≥3 chromosomal aberrations [CAs], CKTs) and highly complex karyotypes (≥5 CAs; hCKTs) as well as specific aberrations in previously untreated patients without TP53 aberrations undergoing either CIT or time-limited venetoclax-based therapies in the phase 3 GAIA/CLL13 trial. Karyotype analyses were available for 895 of 926 patients (96.7%), of whom 153 (17%) had a CKT and 43 (5%) hCKT. In the CIT arm, CKT was associated with shorter progression-free survival (PFS) (hazard ratio [HR] 2.58; 95% confidence interval [95% CI], 1.54-4.32; P < .001) and overall survival (HR, 3.25; 95% CI, 1.03-10.26; P = .044). In the pooled venetoclax arms, a multivariable analysis identified hCKTs (HR, 1.96; 95% CI, 1.03-3.72; P = .041), but not CKTs, as independent adverse prognosticators for PFS. The presence of translocations (unbalanced and/or balanced) was also independently associated with shorter PFSs in the venetoclax arms. CIT led to the acquisition of additional CAs (mean CAs, 2.0-3.4; from baseline to CLL progression), whereas karyotype complexity remained stable after venetoclax-based treatments (2.0, both time points). This analysis establishes highly complex karyotypes and translocations as adverse prognostic factors in the context of venetoclax-based combination treatments. The findings of this study support the incorporation of karyotyping into the standard diagnostic workup of CLL, because it identifies patients at high risk of poor treatment outcomes and thereby improves prognostication. This trial was registered at www.clinicaltrials.gov as #NCT02950051., (© 2023 by The American Society of Hematology.)
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- 2023
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41. The Effectiveness of Bivalent mRNA Omicron Containing Booster Vaccines Among Patients With Hematological Neoplasms.
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Tadmor T, Melamed G, Alapi H, Patalon T, and Rokach L
- Subjects
- Humans, Vaccines, Combined, SARS-CoV-2, RNA, Messenger genetics, COVID-19 prevention & control, Hematologic Neoplasms therapy
- Abstract
Background/aim: Last year was characterized by the appearance of novel SARS-CoV-2 virus variants, mainly the omicron sub-lineages BA.2.12.1, BA.4, and BA.5, which have confirmed resistance to the acquired immune response developed following first-generation mRNA vaccines. Given the ability to use mRNA technology to respond quickly to variant strains, novel bivalent vaccines against novel omicron variants were generated. In the current work, we evaluated the efficacy and safety of novel bivalent mRNA Omicron-containing booster vaccines among patients with hematological neoplasms, including both lymphoproliferative and myeloid malignancies., Patients and Methods: Cohort patients were obtained from electronic medical records of Maccabi Healthcare Services (MHS), the second-largest healthcare organization in Israel. We analyzed the outcome of all patients with hematological neoplasms, between September 21, 2022, and December 31, 2022, who were identified as having SARS-CoV-2 infection based on polymerase chain reaction (PCR) tests. The Kaplan-Meier method was used to compare the proportion of patients hospitalized for SARS-CoV-2 infection within 30 days among recipients and non-recipients of omicron vaccine., Results: During the study period, 472 patients were infected with Omicron. We compared the outcome of 70 patients who received the bivalent mRNA booster to 402 who did not. Fewer bivalent recipients needed COVID-19-related hospitalization [2 of 70 (2.9%)] in comparison to the non-vaccinated cohort [42 of 402 (10.4%)] (p-value=0.0304). This represents an 89% relative risk reduction in COVID-19-related hospitalization in patients with hematological neoplasms. The median duration of hospitalization was 7 days for the non-vaccinated group and 4 for the vaccinated group. A statistically significant increase in ischemic stroke rates due to bivalent mRNA Omicron-containing booster vaccine was not observed., Conclusion: The bivalent Omicron-containing vaccine mRNA booster has a protective effect in preventing and shortening hospitalization in patients with hematological neoplasms with an acceptable safety profile., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2023
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42. Effectiveness of nirmatrelvir plus ritonavir treatment for patients with chronic lymphocytic leukemia during the Omicron surge.
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Tadmor T, Alapi H, and Rokach L
- Subjects
- Humans, Retrospective Studies, Ritonavir therapeutic use, COVID-19 Drug Treatment, Antiviral Agents, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, COVID-19
- Abstract
Patients with chronic lymphoid leukemia (CLL), even in the Omicron era and after vaccination, suffer from persistent COVID-19 infection, higher complications, and mortality compared with the general population. In this study, we evaluated retrospectively the effectiveness of nirmatrelvir + ritonavir among 1080 patients with CLL who were infected with severe acute respiratory syndrome coronavirus 2. Nirmatrelvir administration was associated with a reduction in COVID-19-related hospitalization or death by day 35. Specifically, the rate of COVID-19-related hospitalization or death in the treated group compared with the untreated group was 4.8% (14 out of 292) vs 10.2% (75 out of 733), respectively. Moreover, we report a 69% relative risk reduction in COVID-19-related hospitalization or death in patients with CLL at the age of ≥65 years. Multivariate analysis indicates that patients aged >65 years, patients who received heavy treatment (>2 previous treatments), patients with recent hospitalizations, intravenous immunoglobulin (IVIG) treatment, and comorbidity had significant improvement outcomes after treatment with nirmatrelvir., (© 2023 by The American Society of Hematology.)
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- 2023
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43. Rebound of COVID-19 infection in patients with chronic lymphocytic leukemia treated for SARS-CoV-2 with Nirmatrelvir/Ritonavir or Molnupiravir.
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Tadmor T, Melamed G, Patalon T, Alapi H, and Rokach L
- Subjects
- Humans, SARS-CoV-2, Ritonavir adverse effects, COVID-19 Drug Treatment, Antiviral Agents, COVID-19, Leukemia, Lymphocytic, Chronic, B-Cell complications, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
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- 2023
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44. [HEPATIC MANIFESTATIONS OF CHRONIC LYMPHOCYTIC LEUKEMIA AND CORRELATION WITH PROGNOSIS].
- Author
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Levy Yurkovski I, Shiti Y, and Tadmor T
- Subjects
- Humans, Female, Aged, Male, Retrospective Studies, Prognosis, Hyperbilirubinemia complications, Leukemia, Lymphocytic, Chronic, B-Cell complications, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell epidemiology
- Abstract
Introduction: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Liver function tests (LFT) revealing impairment are described in 5% of CLL patients. Although these effects are described in the literature, their occurrence at the diagnosis of CLL and correlation with prognostic data have rarely been evaluated. We aimed to evaluate the prevalence of impairment of different LFT at CLL diagnosis and its correlation with prognosis., Methods: This is a descriptive observational retrospective study. Diagnostic and prognostic data from CLL patients followed at Bnai Zion Medical Center were collected from charts for the period January 1st, 2000 until October 6, 2020. A t-test for continuous variables, Chi-2 and Fisher-exact tests for discrete variables, and log-rank test for survival analysis, were performed to evaluate prognostic correlations of impaired as compared with normal LFT. The significance level was defined as p value < 0.05., Results: Overall, 153 patients with CLL diagnosed from 2000 until 2020 were included. The median age was 66 (42-89) years, and 62 were women (40.5%). Before CLL treatment initiation, mildly elevated cholestatic enzymes were encountered among 12% patients, while hepatocellular enzymes were elevated in only 2%. After excluding patients with hemolysis, hyperbilirubinemia was found among 5% of the patients. Cholestatic impairment was associated with negative prognostic data, especially increased alkaline phosphatase levels which was associated with a shorter overall survival (p=0.001)., Conclusions: Impairment of cholestatic enzymes and hyperbilirubinemia is not rare before CLL treatment. Despite its mild impairment, it seems to be associated with worse prognosis.
- Published
- 2023
45. Efficacy of front-line ibrutinib versus fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia: A retrospective multicenter "Real-World" study.
- Author
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Levi S, Bronstein Y, Goldschmidt N, Morabito F, Ziv-Baran T, Del Poeta G, Bairey O, Del Principe MI, Fineman R, Mauro FR, Gutwein O, Reda G, Ruchlemer R, Sportoletti P, Laurenti L, Shvidel L, Coscia M, Tadmor T, Varettoni M, Aviv A, Murru R, Braester A, Chiarenza A, Visentin A, Pietrasanta D, Loseto G, Zucchetto A, Bomben R, Olivieri J, Neri A, Rossi D, Gaidano G, Trentin L, Foà R, Cuneo A, Perry C, Gattei V, Gentile M, and Herishanu Y
- Subjects
- Humans, Rituximab therapeutic use, Cyclophosphamide therapeutic use, Vidarabine therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Published
- 2023
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- View/download PDF
46. Incidence and risk factors for central nervous system relapse in patients with primary mediastinal large B-cell lymphoma in the rituximab era.
- Author
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Vassilakopoulos TP, Panitsas F, Mellios Z, Apostolidis J, Michael M, Gurion R, Ferhanoglu B, Hatzimichael E, Karakatsanis S, Dimou M, Kalpadakis C, Katodritou E, Leonidopoulou T, Kotsianidis I, Giatra H, Kanellias N, Sayyed A, Tadmor T, Akay OM, Angelopoulou MK, Horowitz N, Bakiri M, Pangalis GA, Panayiotidis P, and Papageorgiou SG
- Subjects
- Humans, Rituximab therapeutic use, Incidence, Neoplasm Recurrence, Local pathology, Antineoplastic Combined Chemotherapy Protocols adverse effects, Risk Factors, Cyclophosphamide, Vincristine, Doxorubicin, Chronic Disease, Central Nervous System pathology, Central Nervous System Neoplasms drug therapy, Central Nervous System Neoplasms epidemiology, Central Nervous System Neoplasms pathology, Lymphoma, B-Cell drug therapy, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
Central nervous system (CNS) involvement is rare in primary mediastinal large B-cell lymphoma (PMLBCL). We aimed to evaluate the incidence of CNS relapse as first treatment failure event and the effect of the induction chemotherapy regimen, central nervous system - international prognostic index (CNS-IPI) and other clinical and laboratory variables on the risk of CNS relapse in 564 PMLBCL patients treated with immunochemotherapy. Only 17 patients (3.0%) received CNS prophylaxis. During a 55-month median follow-up only 8 patients experienced CNS relapse as first event, always isolated. The 2-year cumulative incidence of CNS relapse (CI-CNSR) was 1.47% and remained unchanged thereafter. The CI-CNSR was not affected by the chemotherapy regimen (R-CHOP or R-da-EPOCH). None of the established International Prognostic Index factors for aggressive lymphomas predicted CNS relapse in PMLBCL. The 2-year CI-CNSR in patients with versus without kidney involvement was 13.3% versus 0.96% (p < 0.001); 14.3% versus 1.13% with versus without adrenal involvement (p < 0.001); and 10.2% versus 0.97% with versus without either kidney or adrenal involvement. CNS-IPI was also predictive (2-year CI-CNSR in high-risk vs. intermediate/low-risk: 10.37% vs. 0.84%, p < 0.001). However, this association may be driven mainly by kidney and/or adrenal involvement. In conclusion, in PMLBCL, CNS relapse is rare and appears to be strongly associated with kidney and/or adrenal involvement., (© 2022 John Wiley & Sons Ltd.)
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- 2023
- Full Text
- View/download PDF
47. Pregnancy Course of 10 Women Diagnosed with Chronic Lymphocytic Leukemia.
- Author
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Tadmor T, Melamed G, Alapi H, Gazit S, Patalon T, and Rokach L
- Subjects
- Pregnancy, Humans, Female, Aged, Retrospective Studies, Leukemia, Lymphocytic, Chronic, B-Cell complications, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Abstract
Pregnancies following diagnosis of chronic lymphocytic leukemia (CLL) are rare events, mainly because the disease is typically diagnosed in the elderly. Literature on the topic is based only on case reports, and limited data are available on the influence of pregnancy on CLL course. In this retrospective study, we aimed to summarize the clinical and laboratory course of 10 women with CLL who became pregnant. None of the patients had significant changes in blood count during or after pregnancy or had complications such as infection, autoimmune phenomenon, or preeclampsia. Four out of 10 pregnancies were terminated with an early miscarriage. Following labor, 1 patient started anti-CLL treatment due to preexisting anemia, but none of the women required therapy during CLL progression during the first 2 years of follow-up. We conclude that based on our serial, pregnancy does not negatively impact on CLL course., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2023
- Full Text
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48. Real-world experience with belantamab mafodotin therapy for relapsed/refractory multiple myeloma: A multicentre retrospective study.
- Author
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Shragai T, Magen H, Lavi N, Gatt M, Trestman S, Zektser M, Ganzel C, Jarchowsky O, Berger T, Tadmor T, Leiba M, Hertzog-Tzarfaty K, Horowitz N, Shapira M, Varssano D, Berger Y, Frenkel S, Krauthammer M, Avivi I, Luttwak E, and Cohen YC
- Subjects
- Humans, Aged, Retrospective Studies, Prospective Studies, Treatment Outcome, Multiple Myeloma drug therapy
- Abstract
Belantamab mafodotin, an immuno-conjugate targeting B-cell maturation antigen, showed single-agent activity in phase 1 and 2 studies, and was recently approved for heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients. Real-world data and long-term follow-up are scarce. We conducted a multisite retrospective study aimed to assess safety and efficacy of belantamab mafodotin monotherapy administered via the GSK expanded access compassionate care programme. One-hundred and six RRMM patients were treated with belantamab mafodotin between July 2019 and March 2021. The median age was 69.4 years. Patients were heavily pretreated with a median of six (range 2-11) prior therapy lines. Major adverse effects included ocular toxicity (keratopathy 68.4%, grade ≥3: 40.5%; blurred vision 36.8%, grade ≥3: 6.3%), thrombocytopenia (27.4%, grade ≥3: 17.9%) and infections (11.3%, grade ≥3: 7.5%). Median follow-up time was 11.9 [95% confidence interval (CI) 10.0-13.8] months. Overall response rate was 45.5%. Median progression-free survival was 4.7 (95% CI 3.5-5.9) months in the entire cohort and 8.8 (95% CI 6.6-10.9) months among responders. Median overall survival was 14.5 (95% CI 9.5-19.6) months, and not reached for responders. To conclude, in a real-world setting, belantamab mafodotin monotherapy showed efficacy comparable with the prospective clinical trials, with a tolerable toxicity profile., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
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49. Clinical Outcomes of COVID-19 in Mycosis Fungoides and Sezary Syndrome.
- Author
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Levy Yurkovski I, Rokach L, Melamed G, Alapi H, Gazit S, Patalon T, and Tadmor T
- Subjects
- Humans, SARS-CoV-2, Mycosis Fungoides complications, Mycosis Fungoides epidemiology, Mycosis Fungoides diagnosis, Sezary Syndrome complications, Sezary Syndrome diagnosis, Sezary Syndrome therapy, Skin Neoplasms diagnosis, Skin Neoplasms therapy, COVID-19 complications, COVID-19 epidemiology
- Abstract
Introduction: Haemato-oncologic patients are more susceptible to severe infections with SARS-CoV-2. We aimed to assess the clinical outcomes of SARS-CoV-2 infection among patients with Mycosis Fungoides and Sezary Syndrome (MF/SS)., Methods: The data were retrieved from anonymized electronic medical records of Maccabi Healthcare Services (MHS), the second-largest healthcare organization in Israel. Patients diagnosed with MF/SS were included in the study. COVID-19 PCR test results together with sociodemographic and clinical data were extracted and analyzed to evaluate the association of COVID-19 with clinical outcomes., Results: In the period of 2020-2022, 1,472 MF/SS patients were included in the study. Among them, 768 (52%) had SARS-CoV-2 infection. The hospitalization rate was 2.9% and infection by the Delta variant was associated with the highest hospitalization rate (7.7%). The hospitalization rate was lower among fully vaccinated patients (p = 0.032) but higher for patients older than 65 (p < 0.001) and patients with SS (vs. MF) (p < 0.001) or COPD (p = 0.024) diagnosis. There was a tendency for decreased hospitalization among patients treated with nirmatrelvir + ritonavir within 5 days of infection, with a 79% risk reduction, although it was not statistically significant (p = 0.164)., Conclusion: Patients with MF/SS do not necessarily have worse COVID-19 outcomes compared to the general population., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2023
- Full Text
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50. Consensus opinion from an international group of experts on measurable residual disease in hairy cell leukemia.
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Ravandi F, Kreitman RJ, Tiacci E, Andritsos L, Banerji V, Barrientos JC, Bhat SA, Blachly JS, Broccoli A, Call T, Chihara D, Dearden C, Demeter J, Dietrich S, Else M, Epperla N, Falini B, Forconi F, Gladstone DE, Gozzetti A, Iyengar S, Johnston JB, Jorgensen J, Juliusson G, Lauria F, Lozanski G, Parikh SA, Park JH, Polliack A, Quest G, Robak T, Rogers KA, Saven A, Seymour JF, Tadmor T, Tallman MS, Tam CS, Thompson PA, Troussard X, Zent CS, Zenz T, Zinzani PL, Wörmann B, Rai K, and Grever M
- Subjects
- Humans, Neoplasm, Residual diagnosis, Neoplasm, Residual genetics, Remission Induction, Genes, Immunoglobulin Heavy Chain, Flow Cytometry, Leukemia, Hairy Cell diagnosis, Leukemia, Hairy Cell genetics, Leukemia, Hairy Cell therapy
- Abstract
A significant body of literature has been generated related to the detection of measurable residual disease (MRD) at the time of achieving complete remission (CR) in patients with hairy cell leukemia (HCL). However, due to the indolent nature of the disease as well as reports suggesting long-term survival in patients treated with a single course of a nucleoside analog albeit without evidence of cure, the merits of detection of MRD and attempts to eradicate it have been debated. Studies utilizing novel strategies in the relapse setting have demonstrated the utility of achieving CR with undetectable MRD (uMRD) in prolonging the duration of remission. Several assays including immunohistochemical analysis of bone marrow specimens, multi-parameter flow cytometry and molecular assays to detect the mutant BRAF V600E gene or the consensus primer for the immunoglobulin heavy chain gene (IGH) rearrangement have been utilized with few comparative studies. Here we provide a consensus report on the available data, the potential merits of MRD assessment in the front-line and relapse settings and recommendations on future role of MRD assessment in HCL., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
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