22 results on '"Bouabdallah, K."'
Search Results
2. Long-term safety and efficacy of the PI3K inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2-year follow-up of the CHRONOS-1 study
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Dreyling, M. Santoro, A. Mollica, L. Leppä, S. Follows, G. Lenz, G. Kim, W.S. Nagler, A. Dimou, M. Demeter, J. Özcan, M. Kosinova, M. Bouabdallah, K. Morschhauser, F. Stevens, D.A. Trevarthen, D. Munoz, J. Rodrigues, L. Hiemeyer, F. Miriyala, A. Garcia-Vargas, J. Childs, B.H. Zinzani, P.L.
- Abstract
Safety profiles of oral PI3K inhibitors have resulted in US FDA black box warnings regarding fatal/serious toxicities. The approved intravenous PI3K inhibitor copanlisib has low incidence of severe toxicities and no black box warnings, but chronic treatment effects were unknown. We provide an update on safety and efficacy of copanlisib with a minimum 2-year follow-up of the CHRONOS-1 study. A total of 142 patients with histologically confirmed indolent B-cell lymphoma who had relapsed after or were refractory to ≥2 prior treatments received intravenous copanlisib 60 mg on days 1, 8, and 15 (28-day cycle). The primary efficacy endpoint was objective response rate (ORR) after ≥4 cycles (independent assessment). The predominant histology was follicular lymphoma (n = 104). The ORR was 60.6% (seven additional complete responses since primary analysis). Secondary endpoints of median duration of response, progression-free survival, and overall survival were 14.1 months (median follow-up, 16.1 months), 12.5 months (median follow-up, 14.0 months), and 42.6 months (median follow-up, 31.5 months), respectively. Median safety follow-up was 6.7 months; 26% of patients received treatment for >1 year. Common treatment-emergent adverse events (TEAEs) (all grade/grade 3/grade 4) were transient hyperglycemia (50.0%/33.1%/7.0%), diarrhea (35.2%/8.5%/0%), transient hypertension (29.6%/23.9%/0%), and neutropenia (28.9%/9.2%/14.8%). Serious AEs were largely unchanged, with no new cases of pneumonitis (4.2%), diarrhea (2.8%), or grade 5 events. Note, TEAEs showed no evidence for increased incidence or worsening following longer exposure in patients treated >1 year. Long-term follow-up of patients with relapsed/refractory indolent B-cell lymphoma treated with intravenous copanlisib demonstrated durable, enhanced responses without evidence of worsening TEAEs, as reported for orally administered PI3K inhibitors. © 2019 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.
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- 2020
3. Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma
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Morschhauser F, Fowler N, Feugier P, Bouabdallah R, Tilly H, Palomba M, Fruchart C, Libby E, Casasnovas R, Flinn I, Haioun C, Maisonneuve H, Ysebaert L, Bartlett N, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica G, Garcia-Sancho A, Lopez-Guillermo A, Larouche J, Ando K, da Silva M, Andre M, Zachee P, Sehn L, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles G, and RELEVANCE Trial Investigators
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- 2018
4. Phosphatidylinositol 3-kinase inhibition by Copanlisib in relapsed or refractory indolent lymphoma
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Dreyling, M. Santoro, A. Mollica, L. Leppä, S. Follows, G.A. Lenz, G. Kim, W.S. Nagler, A. Panayiotidis, P. Demeter, J. Öcan, M. Kosinova, M. Bouabdallah, K. Morschhauser, F. Stevens, D.A. Trevarthen, D. Giurescu, M. Cupit, L. Liu, L. Köchert, K. Seidel, H. Peña, C. Yin, S. Hiemeyer, F. Garcia-Vargas, J. Childs, B.H. Zinzani, P.L.
- Abstract
Purpose: Phosphatidylinositol 3-kinase (PI3K) signaling is critical for the proliferation and survival of malignant B cells. Copanlisib, a pan-class I PI3K inhibitor with predominant activity against PI3K-a and -d isoforms, has demonstrated efficacy and a manageable safety profile in patients with indolent lymphoma. Patients and Methods: In this phase II study, 142 patients with relapsed or refractory indolent lymphoma after two or more lines of therapy were enrolled to receive copanlisib 60 mg intravenously on days 1, 8, and 15 of a 28-day cycle. The primary end point was objective response rate; secondary end points included duration of response, progression-free survival, and overall survival. In addition, safety and gene expression were evaluated. Results: Median age was 63 years (range, 25 to 82 years), and patients had received a median of three (range, two to nine) prior regimens. The objective response rate was 59% (84 of 142 patients); 12% of patients achieved a complete response. Median time to response was 53 days. Median duration of response was 22.6 months, median progression-free survival was 11.2 months, and median overall survival had not yet been reached. The most frequent treatment-emergent adverse events were transient hyperglycemia (all grades, 50%; grade 3 or 4, 41%) and transient hypertension (all grades, 30%; grade 3, 24%). Other grade $3 events included decreased neutrophil count (24%) and lung infection (15%). High response rates to copanlisib were associated with high expression of PI3K/B-cell receptor signaling pathway genes. Conclusion: PI3K-α and -δ inhibition by copanlisib demonstrated significant efficacy and a manageable safety profile in heavily pretreated patients with relapsed or refractory indolent lymphoma. © 2017 by American Society of Clinical Oncology.
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- 2017
5. DESIGN OF A PHYSICAL ACTIVITY PROGRAM TO PREVENT FUNCTIONAL DECLINE IN ONCO-GERIATRIC PATIENTS (CAPADOGE): A RANDOMIZED MULTICENTER TRIAL
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Adélaïde Doussau, Durrieu J, Périé Jl, Robert B, Maget B, Dauba J, Rieger A, Sophie C. Regueme, Isabelle Bourdel-Marchasson, Bouabdallah K, Zwolakowski, Trager S, Mariette C, and Terrebonne E
- Subjects
medicine.medical_specialty ,business.industry ,media_common.quotation_subject ,Cognition ,General Medicine ,law.invention ,Quality of life ,Feeling ,Randomized controlled trial ,Weight loss ,law ,Intervention (counseling) ,Multicenter trial ,Physical therapy ,Medicine ,medicine.symptom ,business ,Balance (ability) ,media_common - Abstract
Background: Cancer in older patient favours the development of frailty: feeling of exhaustion, loss of weight, decreased muscle strength, slow gait speed, and low physical activity. Objectives: To evaluate the efficacy of adapted physical activity phone advices in limiting the cancer-induced loss of autonomy and frailty phenotype development. Design: Multicenter randomized controlled trial. Setting: Patients (>70y) undergoing curative treatment for cancer (n=400) will be recruited from 12 centres. Intervention: The intervention consists in phoned personalized physical activity advices related to strength, aerobic, balance, proprioception, and flexibility. The contacts are performed twice a month during six months and then monthly until 1 year. The intervention complements the PNNS booklet advices (National Nutritional Health Program). The trial compares "individualized phone advices + PNNS" to "usual care + PNNS". Measurements: Functional, cognitive, clinical and self-reported data are assessed before treatment and at 3, 6, 12, 18, and 24 month follow-up. The primary outcome is the proportion of subjects with a one-year decreased SPPB (Short Physical Performance Battery) score of one point or more, as compared to baseline. The secondary outcomes include quality of life items, rate of hospitalizations, institutionalizations, mortality, Fried phenotype at 1 and 2 years, and the SPPB score at 2 years. Discussion: This large trial will provide clinical data of the effects of an exercise advices intervention in older patients during cancer therapy on function and cognition evolution, and quality of life. The possibilities of minimizing the development of frailty phenotype due to these advices will be explored.
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- 2012
6. Aggressive lymphomas with renal involvement: a study of 48 patients treated with the LNH-84 and LNH-87 regimens. Groupe d'Etude des Lymphomes de l'Adulte
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Morel, P., Dupriez, B., Herbrecht, R., Bastion, Y., Tilly, H., Delannoy, A., Haioun, C., Nouvel, C., Bouabdallah, K., and Baumelou, E.
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Adult ,Male ,Adolescent ,Vindesine ,Prednisolone ,Kidney ,Methylprednisolone ,Bleomycin ,Actuarial Analysis ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Lymphoma, Large-Cell, Immunoblastic ,Cyclophosphamide ,Lymphoma, Follicular ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Antibiotics, Antineoplastic ,Chi-Square Distribution ,L-Lactate Dehydrogenase ,Lymphoma, Non-Hodgkin ,Remission Induction ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Prognosis ,Survival Analysis ,Kidney Neoplasms ,Survival Rate ,Methotrexate ,Treatment Outcome ,Doxorubicin ,Creatinine ,Female ,Lymphoma, Large B-Cell, Diffuse ,Research Article - Abstract
In order to describe renal involvement in aggressive non-Hodgkin's lymphomas (NHLs) and its prognostic significance, we reviewed the outcome of 48 patients with renal involvement treated with the LNH-84 or LNH-87 regimen. Histology was diffuse large cell in 29 (60%) patients; immunoblastic, diffuse mixed cell and lymphoblastic in four each; follicular large cell, diffuse small cleaved cell and diffuse small non-cleaved cell in one each; and unclassified in four. Ann Arbor stage was IV in 44 patients, and IE or IIE in four. Tumour mass > or = 10 cm, performance status (ECOG scale) > 2 and increased LDH level were present in 69%, 20% and 76% of patients respectively. Fifteen patients (31%) had multiple intraparenchymal nodules, 14 (29%) had direct spread into the kidney from a perirenal mass, ten (21%) had a single intraparenchymal nodule and nine (19%) had diffuse infiltration. Twenty-one patients (43%) presented with bilateral lesions. Three patients (6%) presented with acute renal failure. Ten other patients (21%) had serum creatinine > 120 mumol l-1. In 12 of these 13 patients renal function was restored with chemotherapy. Twenty-eight patients (57%) achieved complete remission. Estimated 4 year disease-free survival was 39%. Disease-free survival and actuarial survival at 4 years were estimated to be 58% respectively. Two renal parameters had adverse prognostic significance for survival: renal hilum involvement (P = 0.02) and diffuse renal infiltration (P = 0.01). A Cox model identified only two independent prognostic factors for survival, namely performance status > or = 2 and tumour size > or = 10 cm. We conclude that alteration in renal function occurs in 27% of patients with renal involvement. Systemic chemotherapy improves renal function rapidly. Long-term outcome is similar to that expected in NHL patients presenting with the same prognostic factors.
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- 1994
7. Response of iron overload to deferasirox in rare transfusion-dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias
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Porter, Jb, Lin, Kh, Beris, P, Forni, Gl, Taher, A, Habr, D, Domokos, G, Roubert, B, Thein, Sl, EPIC study investigators including Agaoglu, L, Alimena, G, Alonso, D, Ame, S, Angelucci, E, Arrizabalaga, B, Athanasiou Metaxa, M, Augustson, B, Aydinok, Y, Baba, A, Baccarani, M, Beck, J, Beyne Rauzy, O, Birgens, H, Bordessoule, D, Borgna Pignatti, C, Bosly, A, Bouabdallah, K, Bowen, D, Bron, D, Cappellini, Md, Capra, M, Cartron, G, Cazzola, M, Chalkias, C, Chan, Ll, Chancharunee, S, Chapman, C, Charoenkwan, P, Chasapopoulou, E, Cheze, S, Chuansumrit, A, Cianciulli, P, Dauriac, C, Delforge, M, Dölken, G, Dombret, H, Duyster, J, Economopoulos, T, Ehninger, G, Elalfy, M, El Beshlawy, A, Enggaard, L, Fenaux, P, Fillet, G, Filosa, A, Galanello, R, Ganser, A, Gastl, G, Gattermann, N, Giraudier, S, Goldfarb, A, Grigg, A, Guerci Bresler, A, Gumruk, F, Ha, Sy, Haase, D, Heinrich, B, Hertzberg, M, Ho, J, Hsu, Hc, Huang, S, Hunault Berger, M, Inusa, B, Jalumes, D, Jensen, J, Kattamis, A, Kilinc, Y, Kim, Kh, Kinsey, S, Kjeldsen, L, Koren, A, Lai, Me, Lai, Y, Lee, Jw, Lee, Kh, Lee, Sh, Legros, L, Li, C, Li, Ck, Li, Q, Linkesch, W, Lübbert, M, Lutz, D, Mohamed Thalha AJ, Mufti, G, Muus, P, Nobile, F, Ozsahin, H, Papadopoulos, N, Perrotta, S, Petrini, M, Pfeilstöcker, M, Piga, Antonio Giulio, Poole, J, Pungolino, E, Quarta, G, Ravoet, C, Remacha, Af, Rose, C, Roy, L, Saglio, Giuseppe, Sanz, G, Schmid, M, Schmugge, M, Schots, H, Secchi, G, Seymour, Jf, Shah, F, Shah, H, Shen, Z, Slama, B, Sutcharitchan, P, Tamary, H, Taylor, K, Tesch, Hj, Troncy, J, Vassilieff, D, Villegas, A, Viprakasit, V, Wainwright, L, Wassmann, B, Wettervald, M, Will, A, Wörmann, B, Wright, J, Yeh, Sp, Yoon, Ss, Zoumbos, Nc, Zweegman, S., Ozsahin, Ayse Hulya, Porter, Jb, Lin, Kh, Beris, P, Forni, Gl, Taher, A, Habr, D, Domokos, G, Roubert, B, Thein, Sl, on behalf of the EPIC study, Investigator, and Perrotta, Silverio
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safety ,Male ,Iron Overload ,Adolescent ,iron chelation therapy ,Iron ,Iron Chelating Agents/therapeutic use ,Iron Chelating Agents ,Benzoates ,Anemia/drug therapy ,Humans ,Blood Transfusion ,Benzoates/therapeutic use ,Child ,Iron/blood ,ddc:616 ,ddc:618 ,iron overload ,rare anaemias ,serum ferritin ,Ferritins/blood ,Anemia ,Original Articles ,Triazoles ,Deferasirox ,Child, Preschool ,Ferritins ,rare anaemia ,Female ,Triazoles/therapeutic use - Abstract
Objectives: It is widely assumed that, at matched transfusional iron-loading rates, responses to chelation therapy are similar, irrespective of the underlying condition. However, data are limited for rare transfusiondependent anaemias, and it remains to be elucidated if response differs, depending on whether the anaemia has a primary haemolytic or production mechanism. Methods: The efficacy and safety of deferasirox (Exjade) in rare transfusion-dependent anaemias were evaluated over 1 yr, with change in serum ferritin as the primary efficacy endpoint. Initial deferasirox doses were 10–30 mg⁄ kg ⁄ d, depending on transfusion requirements; 34 patients had production anaemias, and 23 had haemolytic anaemias. Results: Patients with production anaemias or haemolytic anaemias had comparable transfusional iron-loading rates (0.31 vs. 0.30 mL red blood cells ⁄ kg ⁄ d), mean deferasirox dosing (19.3 vs. 19.0 mg⁄ kg ⁄ d) and baseline median serum ferritin (2926 vs. 2682 ng ⁄ mL). Baseline labile plasma iron (LPI) levels correlated significantly with the transfusional iron-loading rates and with serum ferritin levels in both cohorts. Reductions in median serum ferritin levels were initially faster in the production than the haemolytic anaemias, but at 1 yr, similar significant reductions of 940 and 617 ng ⁄mL were attained, respectively ()26.0% overall). Mean LPI decreased significantly in patients with production (P < 0.0001) and haemolytic (P = 0.037) anaemias after the first dose and was maintained at normal mean levels (
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- 2011
8. Iron chelation therapy with deferasirox in patients with aplastic anemia: a subgroup analysis of 116 patients from the EPIC trial
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Lee, Jw, Yoon, Ss, Shen, Zx, Ganser, A, Hsu, Hc, Habr, D, Domokos, G, Roubert, B, Porter, Jb, Agaoglu, L, Alimena, G, Alonso, D, Ame, S, Angelucci, E, Arrizabalaga, B, Athanasiou Metaxa, M, Augustson, B, Aydinok, Y, Baba, A, Baccarani, M, Beck, J, Beris, P, Beyne Rauzy, O, Birgens, H, Bordessoule, D, Borgna, Caterina, Bosly, A, Bouabdallah, K, Bowden, D, Bowen, D, Bron, D, Cappellini, Md, Capra, M, Cartron, G, Cazzola, M, Chalkias, C, Chan, Ll, Chancharunee, S, Chapman, C, Charoenkwan, P, Chasapopoulou, E, Cheze, S, Chuansumrit, A, Cianciulli, P, Dauriac, C, Delforge, M, Dölken, G, Dombret, H, Duyster, J, Economopoulos, T, Ehninger, G, Elalfy, M, El Beshlawy, A, Enggaard, L, Fenaux, P, Fillet, G, Filosa, A, Forni, G, Galanello, R, Gastl, G, Gattermann, N, Giraudier, S, Goldfarb, A, Grigg, A, Guerci Bresler, A, Gumruk, F, Ha, Sy, Haase, D, Heinrich, B, Hertzberg, M, Ho, J, Huang, S, Hunault Berger, M, Inusa, B, Jaulmes, D, Jensen, J, Kattamis, A, Kilinc, Y, Kim, Kh, Kinsey, S, Kjeldsen, L, Koren, A, Lai, Me, Lai, Y, Lee, Kh, Lee, Sh, Legros, L, Li, C, Li, Ck, Li, Q, Lin, Kh, Linkesch, W, Lübbert, M, Lutz, D, Mohamed Thalha AJ, Mufti, G, Muus, P, Nobile, F, Papadopoulos, N, Perrotta, S, Petrini, M, Pfeilstöcker, M, Piga, A, Poole, J, Pungolino, E, Quarta, G, Ravoet, C, Remacha, Af, Rose, C, Roy, L, Saglio, G, Sanz, G, Schmid, M, Schmugge, M, Schots, H, Secchi, G, Seymour, Jf, Shah, F, Shah, H, Shen, Z, Slama, B, Sutcharitchan, P, Taher, A, Tamary, H, Taylor, K, Tesch, Hj, Thein, Sl, Troncy, J, Vassilieff, D, Villegas, A, Viprakasit, V, Wainwright, L, Wassmann, B, Wettervald, M, Will, A, Wörmann, B, Wright, J, Yeh, Sp, Zoumbos, Nc, Zweegman, S., Lee, Jw, Yoon, S, Shen, Zx, Ganser, A, Hsu, Hc, Habr, D, Domokos, G, Roubert, B, Porter, Jb, EPIC study, Investigator, and Perrotta, Silverio
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Male ,Biochemistry ,Gastroenterology ,Benzoates ,beta-thalassemia ,chemistry.chemical_compound ,overloaded patients ,oxidative stress ,Prospective Studies ,Prospective cohort study ,pathophysiology ,Beta thalassemia ,complications ,epidemiology ,labile plasma iron ,myelodysplastic syndromes ,serum ferritin ,transfusion-dependent anemias ,Anemia, Aplastic ,Hematology ,Middle Aged ,Tolerability ,Creatinine ,Iron chelation ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,aplastic anemia ,Adolescent ,Anemia ,Immunology ,Iron Chelating Agents ,Young Adult ,Internal medicine ,medicine ,Humans ,Aplastic anemia ,therapy ,business.industry ,Myelodysplastic syndromes ,Deferasirox ,deferasirox ,Cell Biology ,Triazoles ,medicine.disease ,Chelation Therapy ,Surgery ,chemistry ,Ferritins ,business - Abstract
The prospective 1-year Evaluation of Patients' Iron Chelation with Exjade (EPIC) study enrolled a large cohort of 116 patients with aplastic anemia; the present analyses evaluated the efficacy and safety of deferasirox in this patient population. After 1 year, median serum ferritin decreased significantly from 3254 ng/mL at baseline to 1854 ng/mL (P < .001). Decreases occurred in chelation-naive (3229-1520 ng/mL; P < .001, last-observation-carried-forward analysis), and previously chelated (3263-2585 ng/mL; P = .21, last-observation-carried-forward analysis) patients and were reflective of dose adjustments and ongoing iron intake. Baseline labile plasma iron levels were within normal range despite high serum ferritin levels. The most common drug-related adverse events were nausea (22%) and diarrhea (16%). Serum creatinine increases more than 33% above baseline and the upper limit of normal occurred in 29 patients (25%), but there were no progressive increases; concomitant use of cyclosporine had a significant impact on serum creatinine levels. The decrease in mean alanine aminotransferase levels at 1 year correlated significantly with reduction in serum ferritin (r = 0.40, P < .001). Mean absolute neutrophil and platelet counts remained stable during treatment, and there were no drug-related cytopenias. This prospective dataset confirms the efficacy and well characterizes the tolerability profile of deferasirox in a large population of patients with aplastic anemia. This study was registered at www.clinicaltrials.gov as #NCT00171821.
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- 2010
9. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study
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Gattermann, N. Finelli, C. Della Porta, M. Fenaux, P. Ganser, A. Guerci-Bresler, A. Schmid, M. Taylor, K. Vassilieff, D. Habr, D. Domokos, G. Roubert, B. Rose, C. Agaoglu, L. Alimena, G. Alonso, D. Ame, S. Angelucci, E. Arrizabalaga, B. Athanasiou-Metaxa, M. Augustson, B. Aydinok, Y. Baba, A. Baccarani, M. Beck, J. Beris, P. Beyne-Rauzy, O. Birgens, H. Bordessoule, D. Borgna-Pignatti, C. Bosly, A. Bouabdallah, K. Bowden, D. Bowen, D. Bron, D. Cappellini, M.D. Capra, M. Cartron, G. Cazzola, M. Chalkias, C. Chan, L.L. Chancharunee, S. Chapman, C. Charoenkwan, P. Chasapopoulou, E. Cheze, S. Chuansumrit, A. Cianciulli, P. Dauriac, C. Delforge, M. Dölken, G. Dombret, H. Duyster, J. Economopoulos, T. Ehninger, G. Elalfy, M. El-Beshlawy, A. Enggaard, L. Fillet, G. Filosa, A. Forni, G. Galanello, R. Gastl, G. Giraudier, S. Goldfarb, A. Grigg, A. Gumruk, F. Ha, S.Y. Haase, D. Heinrich, B. Hertzberg, M. Ho, J. Hsu, H.-C. Huang, S. Hunault-Berger, M. Inusa, B. Jaulmes, D. Jensen, J. Kattamis, A. Kilinc, Y. Kim, K.-H. Kinsey, S. Kjeldsen, L. Koren, A. Lai, M.E. Lai, Y. Lee, J.-W. Lee, K.-H. Lee, S.-H. Legros, L. Li, C. Li, C.-K. Li, Q. Lin, K.-H. Linkesch, W. Lübbert, M. Lutz, D. Mohamed Thalha, A.J. Mufti, G. Muus, P. Nobile, F. Papadopoulos, N. Perrotta, S. Petrini, M. Pfeilstöcker, M. Piga, A. Poole, J. Porter, J.B. Pungolino, E. Quarta, G. Ravoet, C. Jolimont Lobbes, H.H. Remacha, A.F. Roy, L. Saglio, G. Sanz, G. Schmugge, M. Schots, H. Secchi, G. Seymour, J.F. Shah, F. Shah, H. Shen, Z. Slama, B. Sutcharitchan, P. Taher, A. Tamary, H. Tesch, H.-J. Thein, S.L. Troncy, J. Villegas, A. Viprakasit, V. Wainwright, L. Wassmann, B. Wettervald, M. Will, A. Wörmann, B. Wright, J. Yeh, S.-P. Yoon, S.-S. Zoumbos, N.C. Zweegman, S.
- Abstract
The prospective 1-year EPIC study enrolled 341 patients with myelodysplastic syndromes (MDS); although baseline iron burden was >2500. ng/mL, ∼50% were chelation-naïve. Overall median serum ferritin decreased significantly at 1 year (p=0.002). Decreases occurred irrespective of whether patients were chelation-naïve or previously chelated; changes were dependent on dose adjustments and ongoing iron intake. Sustained reductions in labile plasma iron were observed. Discontinuation rate (48.7%) and adverse event profile were consistent with previously reported deferasirox data in MDS. Alanine aminotransferase levels decreased significantly; change correlated significantly with reduction in serum ferritin (p
- Published
- 2010
10. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study
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Gattermann, N., Finelli, C., Porta, M. D., Fenaux, P., Ganser, A., Guerci Bresler, A., Schmid, M., Taylor, K., Vassilieff, D., Habr, D., Domokos, G., Roubert, B., Rose, C., Agaoglu, L., Alimena, G., Alonso, D., Ame, S., Angelucci, E., Businco, A., Arrizabalaga, B., Athanasiou Metaxa, M., Augustson, B., Aydinok, Y., Baba, A., Baccarani, M., Beck, J., Beris, P., Beyne Rauzy, O., Birgens, H., Bordessoule, D., Borgna, Caterina, Bosly, A., Bouabdallah, K., Bowden, D., Bowen, D., Bron, D., Cappellini, M. D., Capra, M., Cartron, G., Cazzola, M., Chalkias, C., Chan, L. L., Chancharunee, S., Chapman, C., Charoenkwan, P., Chasapopoulou, E., Cheze, S., Chuansumrit, A., Cianciulli, P., Dauriac, C., Delforge, M., Dölken, G., Dombret, H., Duyster, J., Economopoulos, T., Ehninger, G., Elalfy, M., El Beshlawy, A., Enggaard, L., Fillet, G., Filosa, A., Forni, G., Galanello, R., Gastl, G., Giraudier, S., Goldfarb, A., Grigg, A., Gumruk, F., S. Y., Ha, Haase, D., Heinrich, B., Hertzberg, M., Ho, J., Hsu, H. C., Huang, S., Hunault Berger, M., Inusa, B., Jaulmes, D., Jensen, J., Kattamis, A., Kilinc, Y., Kim, K. H., Kinsey, S., Kjeldsen, L., Koren, A., Lai, M. E., Lai, Y., Lee, J. W., Lee, K. H., Lee, S. H., Legros, L., Li, C., C. K., Li, Li, Q., Lin, K. H., Linkesch, W., Lübbert, M., Lutz, D., Mohamed Thalha, A. J., Mufti, G., Muus, P., Nobile, F., Papadopoulos, N., Perrotta, S., Petrini, M., Pfeilstöcker, M., Piga, A., Poole, J., Porter, J. B., Pungolino, E., Quarta, G., Ravoet, C., Jolimont Lobbes, H. H., Remacha, A. F., Roy, L., Saglio, G., Sanz, G., Schmugge, M., Schots, H., Secchi, G., Seymour, J. F., Shah, F., Shah, H., Shen, Z., Slama, B., Sutcharitchan, P., Taher, A., Tamary, H., Tesch, H. J., Thein, S. L., Troncy, J., Villegas, A., Viprakasit, V., Wainwright, L., Wassmann, B., Wettervald, M., Will, A., Wörmann, B., Wright, J., Yeh, S. P., Yoon, S. S., Zoumbos, N. S., Zweegman, S., Gattermann, N, Finelli, C, Porta, Md, Fenaux, P, Ganser, A, GUERCI BRESLER, A, Schmid, M, Taylor, K, Vassilieff, D, Habr, D, Domokos, G, Roubert, B, Rose, C, EPIC study, Investigator, Perrotta, Silverio, Gattermann N, Finelli C, Porta MD, Fenaux P, Ganser A, Guerci-Bresler A, Schmid M, Taylor K, Vassilieff D, Habr D, Domokos G, Roubert B, Rose C, Baccarani M, EPIC study investigators., and Çukurova Üniversitesi
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Male ,Pediatrics ,Cancer Research ,Blood transfusion ,Thalassemia ,medicine.medical_treatment ,Gastroenterology ,Benzoates ,Child ,Hematology ,biology ,Benzoic Acids ,Alanine Transaminase ,Adolescent ,Adult ,Aged ,Blood Transfusion ,Preschool ,Female ,Ferritins ,Humans ,Iron Chelating Agents ,Iron Overload ,Middle Aged ,Myelodysplastic Syndromes ,Triazoles ,Young Adult ,Oncology ,Child, Preschool ,medicine.drug ,medicine.medical_specialty ,Myelodysplastic syndromes ,deferasirox ,iron chelation therapy ,labile plasma iron ,myelodysplastic syndromes ,serum ferritin ,Serum ferritin ,Deferasirox ,Iron chelation therapy ,Labile plasma iron ,Internal medicine ,medicine ,Adverse effect ,iron-overloaded patients ,transfusion ,Labile plasmairon ,business.industry ,medicine.disease ,Discontinuation ,Iron chelationtherapy ,Alanine transaminase ,biology.protein ,business ,Myelodysplastic syndrome - Abstract
PubMedID: 20451251 The prospective 1-year EPIC study enrolled 341 patients with myelodysplastic syndromes (MDS); although baseline iron burden was >2500. ng/mL, ~50% were chelation-naïve. Overall median serum ferritin decreased significantly at 1 year (p=0.002). Decreases occurred irrespective of whether patients were chelation-naïve or previously chelated; changes were dependent on dose adjustments and ongoing iron intake. Sustained reductions in labile plasma iron were observed. Discontinuation rate (48.7%) and adverse event profile were consistent with previously reported deferasirox data in MDS. Alanine aminotransferase levels decreased significantly; change correlated significantly with reduction in serum ferritin (p
- Published
- 2010
11. Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias
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Cappellini, M. D., Porter, J., El Beshlawy, A., C. K., Li, Seymour, J. F., Elalfy, M., Gattermann, N., Giraudier, S., Lee, J. W., Chan, L. L., Lin, K. H., Rose, C., Taher, A., Thein, S. L., Viprakasit, V., Habr, D., Domokos, G., Roubert, B., Kattamis, A., Agaoglu, L., Alimena, G., Alonso, D., Ame, S., Angelucci, E., Businco, A., Arrizabalaga, B., Athanasiou Metaxa, M., Augustson, B., Aydinok, Y., Baba, A., Baccarani, M., Beck, J., Beris, P., Beyne Rauzy, O., Birgens, H., Bordessoule, D., Borgna, Caterina, Bosly, A., Bouabdallah, K., Bowden, D., Bowen, D., Bron, D., Capra, M., Cartron, G., Cazzola, M., Chalkias, C., Chancharunee, S., Chapman, C., Charoenkwan, P., Chasapopoulou, E., Cheze, S., Chuansumrit, A., Cianciulli, P., Dauriac, C., Delforge, M., Dölken, G., Dombret, H., Duyster, J., Economopoulos, T., Ehninger, G., Enggaard, L., Fillet, G., Filosa, A., Forni, G., Galanello, R., Gastl, G., Goldfarb, A., Grigg, A., Gumruk, F., S. Y., Ha, Haase, D., Heinrich, B., Hertzberg, M., Ho, J., Hsu, H. C., Huang, S., Hunault Berger, M., Inusa, B., Jaulmes, D., Jensen, J., Kilinc, Y., Kim, K. H., Kinsey, S., Kjeldsen, L., Koren, A., Lai, M. E., Lai, Y., Lee, K. H., Lee, S. H., Legros, L., Li, C., Li, Q., Linkesch, W., Lübbert, M., Lutz, D., Mohamed Thalha, A. J., Mufti, G., Muus, P., Nobile, F., Papadopoulos, N., Perrotta, S., Petrini, M., Pfeilstöcker, M., Piga, A., Poole, J., Porter, J. B., Pungolino, E., Quarta, G., Ravoet, C., Jolimont Lobbes, H. H., Remacha, A. F., Roy, L., Saglio, G., Sanz, G., Schmugge, M., Schots, H., Secchi, G., Shah, F., Shah, H., Shen, Z., Slama, B., Sutcharitchan, P., Tamary, H., Tesch, H. J., Troncy, J., Villegas, A., Wainwright, L., Wassmann, B., Wettervald, M., Will, A., Wörmann, B., Wright, J., Yeh, S. P., Yoon, S. S., Zoumbos, N. S., and Zweegman, S.
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Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Blood transfusion ,Iron Overload ,Adolescent ,Anemia ,Thalassemia ,medicine.medical_treatment ,Iron chelation therapy ,Transfusion medicine ,Transfusion-dependent anemias ,Hemosiderosis ,Iron Chelating Agents ,Gastroenterology ,Benzoates ,Young Adult ,IRON CHELATION ,Internal medicine ,medicine ,Humans ,Blood Transfusion ,Tissue Distribution ,SERUM FERRITIN ,Chelation therapy ,Prospective Studies ,Child ,Aged ,Aged, 80 and over ,business.industry ,Myelodysplastic syndromes ,Deferasirox ,Hematology ,Middle Aged ,Triazoles ,medicine.disease ,DEFERASOROX ,Deferoxamine ,Child, Preschool ,Ferritins ,Female ,Original Article ,business ,TRANSFUSION-DEPENDENT ANEMIAS ,Iron, Dietary ,medicine.drug - Abstract
Background Following a clinical evaluation of deferasirox (Exjade) it was concluded that, in addition to baseline body iron burden, ongoing transfusional iron intake should be considered when selecting doses. The 1-year EPIC study, the largest ever investigation conducted for an iron chelator, is the first to evaluate whether fixed starting doses of deferasirox, based on transfusional iron intake, with dose titration guided by serum ferritin trends and safety markers, provides clinically acceptable chelation in patients (agedor=2 years) with transfusional hemosiderosis from various types of anemia.The recommended initial dose was 20 mg/kg/day for patients receiving 2-4 packed red blood cell units/month and 10 or 30 mg/kg/day was recommended for patients receiving less or more frequent transfusions, respectively. Dose adjustments were based on 3-month serum ferritin trends and continuous assessment of safety markers. The primary efficacy end-point was change in serum ferritin after 52 weeks compared with baseline.The 1744 patients enrolled had the following conditions; thalassemia (n=1115), myelodysplastic syndromes (n=341), aplastic anemia (n=116), sickle cell disease (n=80), rare anemias (n=43) and other transfused anemias (n=49). Overall, there was a significant reduction in serum ferritin from baseline (-264 ng/mL; P0.0001), reflecting dosage adjustments and ongoing iron intake. The most common (5%) adverse events were gastrointestinal disturbances (28%) and skin rash (10%). Conclusions Analysis of this large, prospectively collected data set confirms the response to chelation therapy across various anemias, supporting initial deferasirox doses based on transfusional iron intake, with subsequent dose titration guided by trends in serum ferritin and safety markers (clinicaltrials.gov identifier: NCT00171821).
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- 2009
12. Kinematical and thermal fields observations associated with the Portevin Le Châtelier effect on an Al-Mg alloy
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Louche, Hervé, Bouabdallah, K., Vacher, Pierre, Coudert, T., Balland, P., Laboratoire SYstèmes et Matériaux pour la MEcatronique (SYMME), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Laboratoire SYstèmes et Matériaux pour la MEcatronique ( SYMME ), and Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] )
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Portevin-Le-Châtelier effect ,Acoustic emission ,[PHYS.MECA.MEMA]Physics [physics]/Mechanics [physics]/Mechanics of materials [physics.class-ph] ,Condensed Matter::Materials Science ,[ PHYS.MECA.MEMA ] Physics [physics]/Mechanics [physics]/Mechanics of materials [physics.class-ph] ,[ SPI.MECA.MEMA ] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Mechanics of materials [physics.class-ph] ,Aluminum magnesium alloy ,otorhinolaryngologic diseases ,Strain field measurement ,Strain localization ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience; This paper presents experimental tensile test results obtained on flat aluminum magnesium alloy samples on a hard machine. The mechanical response, kinematic fields and acoustic emissions were simultaneously obtained in an experimental setup. Propagation instabilities associated with the Portevin-Le-Châtelier effect were observed as localized intense strain increment bands. Depending on the strain rate, A, B or C types were studied on the basis of stress drops, acoustic emission and strain fields. Then the band characteristics (position, orientation, width, thickness reduction, intensity, acoustic emission, principal strain direction) were presented in various strain rate conditions.
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- 2007
13. Bendamustine-Based (BeEAM) conditioning before autologous stem cell transplantation: results of a multicenter study of 474 patients
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Chantepie, S., Sylvain Garciaz, Tchernonog, E., Peyrade, F., Larcher, M-V, Diouf, M., Fornecker, L-M, Houot, R., Gastinne, T., Soussain, C., Malak, S., Tournilhac, O., Delette, C., Ahmad, I., Gac, A-C, Vilque, J-P, Bekadja, M. A., Casasnovas, R-O, Gressin, R., Jaccard, A., Carpentier, B., Garidi, R., Choufi, B., Guidez, S., Tempescul, A., Chauchet, A., Bouabdallah, R., Gyan, E., Yakoub-Agha, I., Bouabdallah, K., Durot, E., and Damaj, G.
14. Phase II study of 3-hour infusion of high dose paclitaxel in refractory and relapsed aggressive non-Hodgkin's lymphomas
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Casasnovas, R. O., Haioun, C., Dumontet, C., Gabarre, J., Richard, B., Lederlin, P., Caillot, D., Stamatoullas, A., Morel, P., Quesnel, B., Jean-Yves Blay, Bouabdallah, K., Gisselbrecht, C., and Grp Etud Lymphomes, Adulte
15. MUTATIONAL ANALYSIS AND LONG TERM OUTCOME IN ADVANCED CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML) TREATED BY DECITABINE: AN UPDATE OF THE GFM-CMML-2007 PHASE II TRIAL
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Braun, T., Itzykson, R., Droin, N., ALINE RENNEVILLE, Renzis, B., Dreyfus, F., Laribi, K., Bouabdallah, K., Cordonnier, C., Recher, C., Vey, N., Bastie, J. N., Beyne-Rauzy, O., Jolie, B., Jourdan, E., Legros, L., Marjanovic, Z., Sanhes, L., Tertian, G., Vaida, I., Gardin, C., Ades, L., Solary, E., and Fenaux, P.
16. Final Results of-the RiPAD plus C Regimen Including Velcade In Front Line Therapy for Elderly Patients with-Mantle Cell Lymphoma. A Phase II Prospective Study of the GOELAMS Group
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remy GRESSIN, Houot, R., Uribe, M. O., Mounier, C., Bouabdallah, K., Alexis, M., Senecal, D., Molless, M. P., Tournilhac, O., Park, S., Rodon, P., El Yamani, A., Sutton, L., Lioure, B., Assouline, D., Harousseau, J. L., Maisonneuve, H., Maugendre, S. C., and Le Gouill, S.
17. Graft versus lymphoma effect for aggressive T-cell lymphomas in adults: A study from the SFGM-TC (Societe Francaise de Greffe de Moelle et de Therapie Cellulaire)
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Le Gouill, S., Milpied, N., Buzyn, A., Latour, R. Peffault, Vernant, J., Mothy, M., Moles, M., Bouabdallah, K., Bulabois, C., Dupuis, J., Rio, B., Yakoub-Agha, I., Attal, M., Tournilhac, O., Didier Blaise, and Michallet, M.
18. Interim Results of the RiPAD plus C Regimen Including Velcade in Front Line Therapy for Elderly Patients with Mantle Cell Lymphoma. A Phase If Prospective Study of the GOELAMS Group
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remy GRESSIN, Maugendre, S. C., Le Gouill, S., Uribe, M. O., Vigier, M. A., Bouabdallah, K., Mounier, C., Tournilhac, O., Rodon, P., El Yamani, A., Sutton, L., Senecal, D., Lioure, B., Assouline, D., Le Mevel, A., Villemagne, B., Dauriac, C., Gardembas, M., Park, S., and Lamy, T.
19. Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma
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Didier Blaise, Tycel Phillips, Jason T. Romancik, Roch Houot, Robert Lowsky, Martina Sollini, Jean Marc Schiano De Colella, Amer Beitinjaneh, Gunjan L. Shah, Lazaros J. Lekakis, Stephen D. Smith, Paolo Corradini, Mohamad Mohty, Maryam Rahimian, Luca Castagna, Taiga Nishihori, Asad Bashey, Talha Badar, Reid W. Merryman, Mehdi Hamadani, Carmelo Carlo-Stella, Dipenkumar Modi, Sally Arai, Kamal Bouabdallah, Valter Torri, Joseph P. McGuirk, Guillaume Manson, Anna Guidetti, Yi-Bin Chen, Hatcher J. Ballard, Julio C. Chavez, Pier Luigi Zinzani, Tatyana Feldman, Sunita Nathan, Anurag K. Singh, Massimo Magagnoli, Marie Pierre Moles-Moreau, Beatrice Casadei, Anthony Serritella, Michael Byrne, Radhakrishnan Ramchandren, Miguel-Angel Perales, Chiara De Philippis, Samantha Jaglowski, Justin Kline, Remy Dulery, Laura Giordano, Alex F. Herrera, Jonathon B. Cohen, Philippe Armand, Armando Santoro, Aspasia Stamatoulas, Stephen M. Ansell, Michael A. Spinner, Lori Dahncke, Corentin Orvain, Chloé Spilleboudt, Geoffrey Shouse, Robin Joyce, Vincent T. Ho, Matthew J. Frigault, Ryan C. Lynch, Uttam Rao, Jakub Svoboda, David A. Bond, Yago Nieto, Dana-Farber Cancer Institute [Boston], Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Università degli Studi di Milano = University of Milan (UNIMI), University of Bologna/Università di Bologna, Ohio State University [Columbus] (OSU), Stanford University, Memorial Sloane Kettering Cancer Center [New York], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], Humanitas University [Milan] (Hunimed), P01 CA23766, U.S. Department of Health & Human Services | National Institutes of Health, U.S. Department of Health & Human Services | National Institutes of Health, 20575, Associazione Italiana per la Ricerca sul Cancro, Università degli Studi di Milano [Milano] (UNIMI), University of Bologna, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Merryman R.W., Castagna L., Giordano L., Ho V.T., Corradini P., Guidetti A., Casadei B., Bond D.A., Jaglowski S., Spinner M.A., Arai S., Lowsky R., Shah G.L., Perales M.-A., De Colella J.M.S., Blaise D., Herrera A.F., Shouse G., Spilleboudt C., Ansell S.M., Nieto Y., Badar T., Hamadani M., Feldman T.A., Dahncke L., Singh A.K., McGuirk J.P., Nishihori T., Chavez J., Serritella A.V., Kline J., Mohty M., Dulery R., Stamatoulas A., Houot R., Manson G., Moles-Moreau M.-P., Orvain C., Bouabdallah K., Modi D., Ramchandren R., Lekakis L., Beitinjaneh A., Frigault M.J., Chen Y.-B., Lynch R.C., Smith S.D., Rao U., Byrne M., Romancik J.T., Cohen J.B., Nathan S., Phillips T., Joyce R.M., Rahimian M., Bashey A., Ballard H.J., Svoboda J., Torri V., Sollini M., De Philippis C., Magagnoli M., Santoro A., Armand P., Zinzani P.L., and Carlo-Stella C.
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,allogenic stem cell transplantation, PD-1 blockade, Hodgkin lymhpoma ,[SDV]Life Sciences [q-bio] ,Programmed Cell Death 1 Receptor ,Salvage therapy ,0302 clinical medicine ,Young adult ,Immune Checkpoint Inhibitors ,ComputingMilieux_MISCELLANEOUS ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Prognosis ,Hodgkin Disease ,3. Good health ,Survival Rate ,surgical procedures, operative ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Allogeneic transplantation ,Cyclophosphamide ,Adolescent ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,Young Adult ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Survival rate ,Aged ,Retrospective Studies ,Salvage Therapy ,business.industry ,Retrospective cohort study ,[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy ,Blockade ,Transplantation ,030104 developmental biology ,Drug Resistance, Neoplasm ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
International audience; Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3-4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population.
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- 2021
20. Copanlisib plus rituximab versus placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (CHRONOS-3): a double-blind, randomised, placebo-controlled, phase 3 trial
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Aryan Hamed, Güray Saydam, Muhit Ozcan, Aruna Mehra, Klaus Geissler, Florian Hiemeyer, Yuankai Shi, Toshiki Uchida, Árpád Szomor, Rinat Galiulin, Lidia Mongay Soler, Fangfang Lv, Eduardo Yanez, Igor Bondarenko, Katya Sapunarova, Matthew J. Matasar, Marcelo Capra, Anjun Cao, Jifeng Feng, Pier Luigi Zinzani, Mihaela Lazaroiu, Krimo Bouabdallah, Jie Jin, Wei Li, Qingyuan Zhang, Wojciech Jurczak, T. Lin, Barrett H. Childs, Ming-Chung Wang, Ross Baker, Matasar M.J., Capra M., Ozcan M., Lv F., Li W., Yanez E., Sapunarova K., Lin T., Jin J., Jurczak W., Hamed A., Wang M.-C., Baker R., Bondarenko I., Zhang Q., Feng J., Geissler K., Lazaroiu M., Saydam G., Szomor A., Bouabdallah K., Galiulin R., Uchida T., Soler L.M., Cao A., Hiemeyer F., Mehra A., Childs B.H., Shi Y., and Zinzani P.L.
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0301 basic medicine ,Male ,medicine.medical_specialty ,Follicular Lymphoma ,Phases of clinical research ,Placebo ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,Double-Blind Method ,law ,immune system diseases ,Recurrence ,Internal medicine ,hemic and lymphatic diseases ,Phosphoinositide-3 Kinase Inhibitor ,Antineoplastic Combined Chemotherapy Protocols ,Indolent Non-Hodgkin Lymphoma ,Medicine ,Humans ,Monoclonal-Antibody Therapy ,Copanlisib ,Aged ,Phosphoinositide-3 Kinase Inhibitors ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Lymphoma, Non-Hodgkin ,Response Assessment ,Quinazoline ,Middle Aged ,medicine.disease ,Lymphoma ,Clinical trial ,030104 developmental biology ,Pyrimidines ,Oncology ,chemistry ,Pyrimidine ,030220 oncology & carcinogenesis ,Quinazolines ,Rituximab ,Female ,business ,medicine.drug ,Human - Abstract
Background Copanlisib, an intravenous pan-class I PI3K inhibitor, showed efficacy and safety as monotherapy in patients with relapsed or refractory indolent non-Hodgkin lymphoma who had received at least two therapies. The CHRONOS-3 study aimed to assess the efficacy and safety of copanlisib plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma. Methods CHRONOS-3 was a multicentre, double-blind, randomised, placebo-controlled, phase 3 study in 186 academic medical centres across Asia, Australia, Europe, New Zealand, North America, Russia, South Africa, and South America. Patients aged 18 years and older with an Eastern Cooperative Oncology Group performance status of no more than 2 and histologically confirmed CD20-positive indolent B-cell lymphoma relapsed after the last anti-CD20 monoclonal antibody-containing therapy and progression-free and treatment-free for at least 12 months, or at least 6 months for patients unwilling or unfit to receive chemotherapy, were randomly assigned (2:1) with an interactive voice-web response system via block randomisation (block size of six) to copanlisib (60 mg given as a 1-h intravenous infusion on an intermittent schedule on days 1, 8, and 15 [28-day cycle]) plus rituximab (375 mg/m(2) given intravenously weekly on days 1, 8, 15, and 22 during cycle 1 and day 1 of cycles 3, 5, 7, and 9) or placebo plus rituximab, stratified on the basis of histology, progression-free and treatment-free interval, presence of bulky disease, and previous treatment with PI3K inhibitors. The primary outcome was progression-free survival in the full analysis set (all randomised patients) by masked central review. Safety was assessed in all patients who received at least one dose of any study drug. This study is registered with ClinicalTrials.gov, NCT02367040 and is ongoing. Findings Between Aug 3, 2015, and Dec 17, 2019, 652 patients were screened for eligibility. 307 of 458 patients were randomly assigned to copanlisib plus rituximab and 151 patients were randomly assigned to placebo plus rituximab. With a median follow-up of 19.2 months (IQR 7.4-28.8) and 205 total events, copanlisib plus rituximab showed a statistically and clinically significant improvement in progression-free survival versus placebo plus rituximab; median progression-free survival 21.5 months (95% CI 17.8-33.0) versus 13.8 months (10.2-17.5; hazard ratio 0.52 [95% CI 0.39-0.69]; p, Bayer, Bayer.
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- 2021
21. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma
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Dominique Bron, Catherine Thieblemont, Umberto Vitolo, M Neves, Kim Linton, Martin Dreyling, Igor Gorbatchevsky, Pier Luigi Zinzani, J. Garcia-Vargas, David Cunningham, Li Liu, Carol Peña, Karl Koechert, M. Giurescu, Barrett H. Childs, Sarit Assouline, Krimo Bouabdallah, Gregor Verhoef, Florian Hiemeyer, Franck Morschhauser, Dreyling, M, Morschhauser, F, Bouabdallah, K, Bron, D, Cunningham, D, Assouline, S. E, Verhoef, G, Linton, K, Thieblemont, C, Vitolo, U, Hiemeyer, F, Giurescu, M, Garcia-Vargas, J, Gorbatchevsky, I, Liu, L, Koechert, K, Peña, C, Neves, M, Childs, B. H, Zinzani, P. L., Klinikum der Universität [München], Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Bordeaux [Bordeaux], Ecole de Santé Publique [Université Libre de Bruxelles], Université libre de Bruxelles (ULB), IBM Thomas J. Watson Research Center, IBM, Jewish General Hospital, University Hospitals Leuven [Leuven], Manchester University NHS Foundation Trust (MFT), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli studi di Torino (UNITO), Bayer Pharma AG [Berlin], Bayer HealthCare Pharmaceuticals Inc [Whippany], University of Bologna, Università degli studi di Torino = University of Turin (UNITO), University of Bologna/Università di Bologna, Université de Lille, CHU Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - EA 7365, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA], Manchester University NHS Foundation Trust [MFT], Hopital Saint-Louis [AP-HP] [AP-HP], and Università degli studi di Torino = University of Turin [UNITO]
- Subjects
Male ,0301 basic medicine ,Pathology ,copanlisib ,Lymphoma ,[SDV]Life Sciences [q-bio] ,Follicular lymphoma ,Phases of clinical research ,Aggressive lymphoma ,Gastroenterology ,Phosphatidylinositol 3-Kinases ,chemistry.chemical_compound ,0302 clinical medicine ,Recurrence ,Phosphoinositide-3 Kinase Inhibitors ,Aged, 80 and over ,Haematologic Malignancies ,Manchester Cancer Research Centre ,treatment ,Lymphoma, Non-Hodgkin ,Malignant lymphoma ,Hematology ,Middle Aged ,Hodgkin Disease ,3. Good health ,Oncology ,030220 oncology & carcinogenesis ,Female ,Rituximab ,malignant lymphoma ,medicine.drug ,medicine.medical_specialty ,Antineoplastic Agents ,PI3K inhibitor ,Neutropenia ,03 medical and health sciences ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Survival analysis ,Aged ,Copanlisib ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,PTEN Phosphohydrolase ,Original Articles ,medicine.disease ,Isoflavones ,Survival Analysis ,Treatment ,Editor's Choice ,Pyrimidines ,030104 developmental biology ,chemistry ,Quinazolines ,business ,Hématologie - Abstract
Background: Copanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms. Patients and methods: This phase II study evaluated the response rate of copanlisib administered intravenously on days 1, 8, and 15 of a 28-day cycle, in patients with indolent or aggressive malignant lymphoma. Archival tumor tissues were used for immunohistochemistry, gene-expression profiling, and mutation analysis. Results: Thirty-three patients with indolent lymphoma and 51 with aggressive lymphoma received copanlisib. Follicular lymphoma (48.5%) and peripheral T-cell lymphoma (33.3%) were the most common histologic subtypes. Most patients (78.6%) had received prior rituximab and 54.8% were rituximab-refractory. Median duration of treatment was 23 and 8 weeks in the indolent and aggressive cohorts, respectively (overall range 2-138). Eighty patients were evaluated for efficacy. The objective response rate was 43.7% (14/32) in the indolent cohort and 27.1% (13/48) in the aggressive cohort; median progression-free survival was 294 days (range 0-874) and 70 days (range 0-897), respectively; median duration of response was 390 days (range 0-825) and 166 days (range 0-786), respectively. Common adverse events included hyperglycemia (57.1%; grade ≥3, 23.8%), hypertension (54.8%; grade ≥3, 40.5%), and diarrhea (40.5%; grade ≥3, 4.8%), all generally manageable. Neutropenia occurred in 28.6% of patients (grade 4, 11.9%). Molecular analyses showed enhanced antitumor activity in tumors with upregulated phosphatidylinositol 3-kinase pathway gene expression. Conclusion: Intravenous copanlisib demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma. Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell, and mantle cell lymphomas are ongoing., SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2017
22. A multicenter phase II trial (SAKK 36/06) of single-agent Everolimus(RAD001) in patients with relapsed or refractory mantle cell lymphoma
- Author
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Christoph Renner, Emmanuel Gyan, Pier Luigi Zinzani, Pierre-Yves Dietrich, Remy Gressin, Krimo Bouabdallah, Peter Brauchli, Walter Mingrone, Andreas Lohri, Mario Bargetzi, Felicitas Hitz, Nicolas Ketterer, Dirk Klingbiel, Andreas Trojan, Giovanni Martinelli, Sergio Cogliatti, Francesco Bertoni, Michele Ghielmini, Christine Biaggi, Renner C, Zinzani P.L., Gressin R, Klingbiel D, Dietrich PY, Hitz F, Bargetzi M, Mingrone W, Martinelli G, Trojan A, Bouabdallah K, Lohri A, Gyan E, Biaggi C, Cogliatti S, Bertoni F, Ghielmini M, Brauchli P, Ketterer N., Swiss SAKK, French GOELAMS group from European Mantle Cell Lymphoma Network, University of Zurich, and Renner, C
- Subjects
Male ,medicine.medical_treatment ,2720 Hematology ,Lymphoma, Mantle-Cell ,Gastroenterology ,Recurrence ,Clinical endpoint ,Prospective Studies ,ddc:616 ,Aged, 80 and over ,TOR Serine-Threonine Kinases/antagonists & inhibitors ,TOR Serine-Threonine Kinases ,Remission Induction ,Hematology ,Middle Aged ,Neoplasm Proteins ,Refractory Mantle Cell Lymphoma ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Neoplasm Proteins/antagonists & inhibitors ,mantle cell lymphoma ,610 Medicine & health ,Lymphoma, Mantle-Cell/drug therapy/mortality ,Neutropenia ,Disease-Free Survival ,Drug Administration Schedule ,Multicenter trial ,Internal medicine ,Protein Kinase Inhibitors/administration & dosage/adverse effects ,medicine ,Humans ,Protein Kinase Inhibitors ,RAD001 ,Aged ,Neoplasm Staging ,Sirolimus ,Chemotherapy ,Everolimus ,business.industry ,medicine.disease ,everolimus ,Sirolimus/administration & dosage/adverse effects/analogs & derivatives ,Surgery ,relapsed ,refractory ,10032 Clinic for Oncology and Hematology ,Mantle cell lymphoma ,Original Articles and Brief Reports ,business - Abstract
Background Mantle cell lymphoma accounts for 6% of all B-cell lymphomas and is generally incurable. It is characterized by the translocation t(11;14) leading to cyclin D1 over-expression. Cyclin D1 is downstream of the mammalian target of rapamycin threonine kinase and can be effectively blocked by mammalian target of rapamycin inhibitors. We set out to examine the single agent activity of the orally available mammalian target of rapamycin inhibitor everolimus in a prospective, multicenter trial in patients with relapsed or refractory mantle cell lymphoma ([NCT00516412][1]). Design and Methods Eligible patients who had received a maximum of three prior lines of chemotherapy were given everolimus 10 mg for 28 days (one cycle) for a total of six cycles or until disease progression. The primary endpoint was the best objective response. Adverse reactions, progression-free survival and molecular response were secondary endpoints. Results Thirty-six patients (35 evaluable) were enrolled and treatment was generally well tolerated with Common Terminology Criteria grade ≥3 adverse events (>5%) including anemia (11%), thrombocytopenia (11%) and neutropenia (8%). The overall response rate was 20% (95% CI: 8–37%) with two complete remissions and five partial responses; 49% of the patients had stable disease. At a median follow-up of 6 months, the median progression-free survival was 5.5 months (95% CI: 2.8–8.2) overall and 17.0 (6.4–23.3) months for 18 patients who received six or more cycles of treatment. Three patients achieved a lasting complete molecular response, as assessed by polymerase chain reaction analysis of peripheral blood. Conclusions Everolimus as a single agent is well tolerated and has anti-lymphoma activity in relapsed or refractory mantle cell lymphoma. Further studies of everolimus in combination with chemotherapy or as a single agent for maintenance treatment are warranted. ([Clinicaltrials.gov][2] identifier: [NCT00516412][1]) [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00516412&atom=%2Fhaematol%2F97%2F7%2F1085.atom [2]: http://Clinicaltrials.gov
- Published
- 2012
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