20 results on '"Beatrice, Casadei"'
Search Results
2. Critical Role of Hodgkin Lymphoma Cells-Derived Large and Small Extracellular Vesicles in the Regulation of the Immune-Inflammatory Microenvironment
- Author
-
Filippo Maltoni, Chiara Ciardiello, Laura Nanni, Martina Barone, Ghazal Narimanfar, Beatrice Casadei, Lisa Argnani, Alessandro Broccoli, Dorian Forte, Alfredo Budillon, Pier Luigi Zinzani, and Lucia Catani
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
3. Rituximab As an Effective Salvage Therapy in Pretreated Hairy Cell Leukemia Patients: The Bologna Experience
- Author
-
Alessandro Broccoli, Lisa Argnani, Laura Nanni, Gianmarco Bagnato, Matteo Carella, Beatrice Casadei, Paolo Elia Coppola, Gabriele Gugliotta, Ginevra Lolli, Marianna Gentilini, Alice Morigi, Cinzia Pellegrini, Vittorio Stefoni, and Pier Luigi Zinzani
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
4. Gut Microbiota Role in Response to Checkpoint Inhibitor Treatment in Patients with Relapsed/Refractory B-Cell Hodgkin Lymphoma: The MICRO-Linf Study
- Author
-
Patrizia Brigidi, Silvia Turroni, Beatrice Casadei, Monica Barone, Serafina Guadagnuolo, Pier Luigi Zinzani, and Lisa Argnani
- Subjects
biology ,business.industry ,Immune checkpoint inhibitors ,Immunology ,Cell Biology ,Hematology ,Gut flora ,biology.organism_classification ,Biochemistry ,medicine.anatomical_structure ,Relapsed refractory ,Cancer research ,medicine ,Hodgkin lymphoma ,In patient ,business ,B cell - Abstract
Single-agent monoclonal antibodies targeting the immune checkpoint PD1 (programmed death 1) are an efficient and safe therapeutic option in patients with relapsed/refractory B-cell lymphoma. However, many patients progress or lose response to anti-PD1. Recent studies have highlighted the role of the gut microbiota (GM) in influencing the response to chemo-immunotherapeutic agents. Here we hypothesize that the GM dynamics in B-cell lymphoma patients during anti-PD1 therapy correlate with treatment response. From December 2017 to December 2020, we enrolled 17 patients (12 with classical Hodgkin lymphoma [cHL] and 5 with primary mediastinal B-cell lymphoma [PMBCL]) treated with anti-PD1 due to relapsed/refractory disease. Feces were collected at baseline, before each therapy cycle, at response assessment (both during therapeutic course and at the end of treatment) and for grade >2 adverse events. All the samples were profiled through Illumina sequencing. At each time point, patients compiled a 7-day weighted food intake record that was analyzed by MètaDieta (METEDA). We report the results of the first 6 patients enrolled, all affected by cHL. Of the six patients, five were females. The median age was 31 years (range 26-71). Five patients were refractory to the last therapy, with a median of previous treatments of 3 (range 3-5). All the six patients discontinued the chemo-immunotherapy. In particular, three patients were discontinued due to disease progression, two achieved a complete remission and consolidated the response with autologous stem cell transplantation and the last one discontinued due to a grade 3 adverse event, despite partial remission. The median number of anti-PD1 cycles was 15 (range 7-18). The baseline GM was found to be distinct from that of age-/gender-matched healthy controls (HC). In particular, the Bray-Curtis dissimilarity index showed significant segregation between the two study groups (p value < 1×10 -4, PERMANOVA), as well as greater dispersion in the patient group. Regarding intra-individual diversity, although no significant differences were found with both metrics used (Inverse Simpson and Shannon index, Wilcoxon test), a slight decrease in patients compared to HC was observed. By analyzing the genus-level composition, compared to HC, the microbial ecosystem of patients was enriched in the pathobiont Collinsella while depleted of health-associated taxa, e.g., Faecalibacterium, Ruminococcus, Coprococcus and Roseburia (p value < 0.05; Figure 1A). When focusing the analysis on the GM trajectories along the checkpoint inhibitor treatment (Figure 1B), we found that intra-individual variability underwent cyclical fluctuations in responders, while values remained nearly constant in non-responders. Furthermore, significant differences were found between the GM structures of the two patient groups (responders vs non-responders), both at the level of dominant (weighted UniFrac, p value = 0.02) and subdominant (unweighted UniFrac, p value = 0.01) microbial components. The analysis of the questionnaires on eating habits filled in by the patients at each time point made it possible to estimate the daily consumption of the main macronutrients. Despite comparable energy intake and protein and fiber consumption, a greater lipid consumption and lower carbohydrate consumption were observed in responders than in non-responders. In conclusion, the GM of patients affected by B-cell Hodgkin lymphoma showed some peculiarities compared to the HC microbiota, with a depletion of health-promoting microbial components, including producers of short-chain fatty acids (i.e., Faecalibacterium, Roseburia, Coprococcus and Ruminococcus). During therapy, a peculiar trend of GM response emerged in patients with different therapeutic outcomes. Beyond the different structures in terms of dominant and subdominant microbial components, responders showed greater biodiversity plasticity than non-responders. This difference possibly suggests a lower resilience of the disease state. Furthermore, the responder group showed a greater consumption of lipids and a lower intake of carbohydrates during therapy, opening interesting perspectives towards the development of integrated intervention strategies in this peculiar setting. Figure 1 Figure 1. Disclosures Zinzani: GILEAD: Other: Advisory board, Speakers Bureau; MSD: Consultancy, Other: Advisory board, Speakers Bureau; TAKEDA: Other: Advisory board, Speakers Bureau; TG Therapeutics: Other: Advisory board, Speakers Bureau; BMS: Other: Advisory board, Speakers Bureau; Beigene: Other, Speakers Bureau; Incyte: Other, Speakers Bureau; SANDOZ: Other: Advisory board; ADC Therap.: Other; JANSSEN-CILAG: Other: Advisory board, Speakers Bureau; CELLTRION: Other: Advisory board, Speakers Bureau; EUSAPHARMA: Consultancy, Other, Speakers Bureau; KYOWA KIRIN: Other, Speakers Bureau; NOVARTIS: Consultancy, Other, Speakers Bureau; SERVIER: Other: Advisory board, Speakers Bureau; ROCHE: Other, Speakers Bureau; VERASTEM: Consultancy, Other: Advisory board, Speakers Bureau.
- Published
- 2021
5. Real-Life CAR-T Cell Treatment in Large B-Cell Lymphomas Indicates That Axi-Cel and Tisa-Cel Have Similar Outcomes, but Long-Term Cytopenia Is an Emerging Problem
- Author
-
Pier Luigi Zinzani, Patrizia Chiusolo, Massimo Martino, Annalisa Chiappella, Matteo Carrabba, Cristiana Carniti, Paolo Corradini, Enrico Orciuolo, Domenico Russo, Armando Santoro, Vincenzo Perriello, Riccardo Saccardi, Anna Maria Barbui, Stefania Bramanti, Beatrice Casadei, Maria Chiara Tisi, Rosalba Miceli, Anna Guidetti, Alice Di Rocco, Barbara Botto, Silva Ljevar, and Anna Dodero
- Subjects
Cytopenia ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Term (time) ,medicine.anatomical_structure ,Cancer research ,Medicine ,Car t cells ,business ,B cell - Abstract
Introduction. The outcome of relapsed/refractory large B-cell lymphomas, not eligible or cured by high dose chemotherapy due to persistent disease, is very unsatisfactory. The introduction of anti-CD19 chimeric antigen receptor T cells (CAR-T) in this setting, showed impressive long-term results in registrative trials. Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are registered and reimbursed in Italy by Agenzia Italiana del Farmaco (AIFA) for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) patients after at least 2 lines, with an ECOG 0-1, and an age lower than 71 years. To evaluate in real-life the patients treated in Italy with CAR-T cells, the Italian Society of Hematology (SIE) designed an observational study. Methods. The CART-SIE is an ongoing prospective and retrospective observational trial with the following aims: 1. consecutively register all DLBCL and PMBCL treated in the Italian authorized centers; 2. evaluate the intention to treat overall response rate (ORR, complete [CR] and partial response [PR]), duration of response (DOR), progression free survival (PFS) and overall survival (OS); 3. evaluate safety in terms of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and long-term cytopenia; 4. compare the two different CAR-T products. Primary endpoint was to evaluate the overall response and survival at one year of the patients receiving CAR-T cells. Results. Since March 2019 to June 2021, 208 patients were enrolled and leukapheresed; 191 patients were infused (92%); 17 were not due to rapidly progressive disease and worsening of clinical conditions (11), severe infection (4), persistent complete remission (1) and manufacturing failure (1). Clinical characteristics of the 191 infused patients were: median age 53 years (range 19-70), stage III/IV 127 (69%); median number of prior lines was 3 (2-12), including 58 (30%) with prior autologous stem cell transplantation. According to local pathology reports, 134 (70%) were DLBCL, 22 (12%) high-grade B-cell lymphoma (HGBCL) and 35 (18%) PMBCL. Bridging therapy was delivered to 177 (93%) patients: 45 (25%) radiotherapy, 115 (65%) systemic therapy (chemotherapy and/or immunotherapy), 17 (10%) combined therapy (radiotherapy + chemotherapy). All patients received Fludarabine-Cyclophosphamide as lymphodepletion regimen. Axi-cel was infused in 92 (48%), and tisa-cel in 99 (52%) patients. Median follow-up time for infused patients was 7.66 months (IQR: 4.14-14.74). All 191 patients were evaluable for response at 30-days after the infusion: 84 (44%) CR, 61 (32%) PR, with an ORR of 76%. Median DOR was not reached for CR and PR patients, but CR patients did better than PRs (p=0.04). In the whole series, 6 and 12-months PFS were 56% (95% CI:49-65) and 47% (95%CI:39-56); 6 and 12-months OS were 80% (95%CI:74-87); 71% (95%CI:63-80), respectively. The 6-months PFS and OS by histotype were: 52% (95% CI: 44-62) and 79% (95% CI: 72-87) for DLBCL, 57% (95% CI: 39-83) and 72% (95% CI: 54-97) for HGBCL, 73% (95% CI: 59-90) and 87% (95% CI: 76-99) for PMBCL. No outcome differences between axi-cel and tisa-cel were reported: 6-months PFS and OS were 58% (95% CI: 48-70) and 81% (95% CI: 73-91) vs. 55% (95% CI: 45-66) and 79% (95% CI: 70-88), respectively. Of note, tisa-cel was not used in PMBCL. Severe (grade 3-4) CRS was observed in only 9 (5%) patients, and severe ICANS in 15 (8%). One-hundred and eight (57%) patients received at least one dose of tocilizumab and 62 (33%) received steroids; 24 (13%) patients were admitted in intensive care unit. Cytopenia beyond 90 days was reported in 59 of 179 (33%) evaluable patients. At the time of the analysis, 43 (23%) patients had died, 39 due to lymphoma progression, 4 due to complications related to subsequent therapies. Conclusions. In CART-SIE study, the outcome of patients treated with CAR-T was similar to those of the registrative trials. No differences across histotypes and commercial CAR-T products (axi-cel and tisa-cel) were observed. CRS and ICANS in real world are manageable with adequate risk management plan. Cytopenias are emerging problems in real-life setting. Disclosures Chiappella: Gilead Sciences: Other: lecture fee, advisory board; Roche: Other: lecture fee, advisory board; Takeda: Other: advisory board; Clinigen: Other: lecture fee, advisory board; Celgene Bristol Myers Squibb: Other: lecture fee, advisory board; Astrazeneca: Other: lecture fee; Janssen: Other: lecture fee, advisory board; Incyte: Other: lecture fee; Novartis: Other: lecture fee; Servier: Other: lecture fee. Santoro: Eli-Lilly: Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau; Arqule: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Roche: Speakers Bureau; AbbVie: Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Sanofi: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tisi: Incyte: Membership on an entity's Board of Directors or advisory committees; BWS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Perriello: Novartis: Other: Advisory Board. Corradini: AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Consultancy; AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Honoraria; KiowaKirin; Incyte; Daiichi Sankyo; Janssen; F. Hoffman-La Roche; Kite; Servier: Consultancy; Amgen; Takeda; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations; Novartis; Gilead; Celgene: Consultancy, Other: Travel and accommodations; BMS: Other: Travel and accommodation; Sanofi: Consultancy, Honoraria; Incyte: Consultancy; Novartis, Janssen, Celgene, BMS, Takeda, Gilead/Kite, Amgen, AbbVie: Other: travel and accomodations.
- Published
- 2021
6. Safety and Efficacy of Allogeneic Hematopoietic Stem Cell Transplant after Programmed Cell Death 1 (PD-1) / Programmed Cell Death Ligand 1 (PD-L1) Blockade for Classical Hodgkin Lymphoma: Analysis of a Large International Cohort
- Author
-
Philippe Armand, Asad Bashey, Stephen D. Smith, Pier Luigi Zinzani, Tatyana Feldman, Talha Badar, Alex F. Herrera, Roch Houot, Valter Torri, Corentin Orvain, Anna Guidetti, Joseph P. McGuirk, Uttam Rao, Marie-Pierre Moles, Michael Byrne, Geoffrey Shouse, Matthew J. Frigault, Jonathon B. Cohen, Armando Santoro, Jean Marc Schiano De Colella, Robin Joyce, Carmelo Carlo-Stella, Guillaume Manson, Yago Nieto, Didier Blaise, Sally Arai, Lori Dahncke, Robert Lowsky, Anurag K. Singh, Vincent T. Ho, Stephen M. Ansell, Chiara De Philippis, Maryam Rahimian, Martina Sollini, Luca Castagna, David A. Bond, Reid W. Merryman, Paolo Corradini, Michael A. Spinner, Hatcher J. Ballard, Kamal Bouabdallah, Massimo Magagnoli, Jason T. Romancik, Mohamad Mohty, Mehdi Hamadani, Remy Dulery, Laura Giordano, Chloé Spilleboudt, Beatrice Casadei, Samantha Jaglowski, Yi-Bin Chen, Aspasia Stamatoulas Bastard, Ryan C. Lynch, and Jakub Svoboda
- Subjects
biology ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Pembrolizumab ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Lymphoma ,Avelumab ,Apoptosis ,PD-L1 ,biology.protein ,Cancer research ,Medicine ,Nivolumab ,Stem cell ,business ,medicine.drug - Abstract
Introduction: Anti-PD-1 monoclonal antibodies (mAbs) are highly active in relapsed/refractory classical Hodgkin lymphoma (cHL), but most patients (pts) will still relapse. Given this, allogeneic stem cell transplantation (alloHSCT) remains an important option for pts after PD-1 blockade, as it offers the possibility of cure. Prior reports have suggested that alloHSCT after PD-1 mAbs may be associated with severe immune-related complications including acute graft-versus-host disease (GVHD), veno-occlusive disease (VOD) and cytokine release/febrile non-infectious syndrome (CRS). Prior studies of alloHSCT after PD-1 blockade in cHL have been limited by the small number of pts and short follow-up, preventing an accurate assessment of long-term outcomes and complications, risk factors for early toxicity, and the impact of transplant strategies such as choice of GVHD prophylaxis. We therefore assembled a large retrospective international cohort of cHL pts who underwent alloHSCT after PD-(L)1 blockade to better answer these questions, including an assessment of the impact of post-transplant cyclophosphamide (PTCy) on efficacy and toxicity. Methods: Medical records and databases were reviewed at 26 European and United States transplant centers to identify pts with cHL who underwent an alloHSCT any time after receiving a PD-1 or PD-L1 mAb. Response assessment was performed by local investigators according to Lugano 2014 criteria. Overall survival (OS), progression-free survival (PFS), cumulative incidence (CumInc) of relapse (CIR), non-relapse mortality (NRM), acute (a) and chronic (c) GVHD were estimated, as was the association between baseline variables and these outcomes. Results: Between 2014 and 2019, 150 pts were identified who underwent alloHSCT after a median of 10 (range, 1-74) doses of nivolumab (n=118), pembrolizumab (n=31), or avelumab (n=1). The median age was 31 (range 17-68) and pts had received a median of 4 (range, 2-11) lines of therapy prior to PD-(L)1 blockade. 138 pts (92%) had failed BV and 111 (74%) autologous HSCT. The best overall response to PD-(L)1 mAbs was CR for 62 pts (41%), PR for 55 (37%), SD for 17 (11%), PD for 15 (10%) and unknown for 1 (1%). Median time from last dose of PD-(L)1 mAb to alloHSCT was 80 days (range, 17-756) with 70 pts (47%) receiving intervening systemic therapy. At alloHSCT, 90 pts were in CR (60%), 45 in PR (30%), 5 in SD (3%), and 10 in PD (7%). Donors were haploidentical (n=71, 47%), matched sibling (n=29, 19%), matched unrelated (n=39, 26%), mismatched unrelated (n=7, 5%), cord blood (n=2, 1%), or unknown (n=2, 1%). Stem cell source was bone marrow (n=38, 25%), peripheral blood (n=110, 73%), or cord blood (n=2, 1%). GVHD prophylaxis included PTCy in 88 pts (59%) (69/71 (97%) with haploidentical donors; 19/79 (24%) with other donors). With a median post-alloHSCT follow-up for survivors of 23.8 months (range, 1-67), the 2y OS and PFS were 79% (95CI 71-86%) and 65% (95CI 55-73%), respectively, while the 2y CumIncs of relapse and NRM were 21% (95CI 13-29%) and 14%, (95CI, 8-22%), respectively (Fig. 1A-B). 27 pts have died, 3 due to disease and 24 to NRM, including aGVHD (n=7) and VOD (n=2). Veno-occlusive disease (VOD) occurred in 5 pts (day 100 CumInc 4%) and 29 pts (19%) developed CRS (grade 1 n=16; grade 2 n=7; grade 3 n=4; grade 4 n=2). The 6-month CumIncs of grade 2-4, grade 3-4 and grade 4 aGVHD were 39%, 16% and 8%, respectively. Hyperacute GVHD (onset ≤ 14 days after alloHSCT) occurred in 4% of pts and was fatal in 2 pts. The 2y CumInc of cGVHD was 45%. Neither receipt of > 10 doses (median) of anti-PD-(L)1 mAb nor undergoing alloHSCT ≤80 days (median) after last dose of PD-(L)1 mAb were associated with PFS or OS. However, pts with a shorter time to transplant (≤80 days) appeared to have a higher risk of severe (grade 3-4) aGVHD (6m CumInc 24% vs 9%, p=0.006). Recipients of PTCy in this cohort had lower 2y CumIncs of cGVHD (34% vs 58%, p=0.01) and relapse (12% vs 31%, p=0.02), superior 2y PFS (76% vs 54%, p=0.015), and similar rates of severe aGVHD (15% vs 18%, p=0.5), 2y NRM (12% vs 16%, p=0.5), and 2y OS (82% vs 78%, p=0.6). Conclusions: With extended follow-up of a large international cohort, our results argue that alloSCT performed after PD-(L)1 mAbs is a feasible strategy associated with an excellent PFS and a very low CIR for this disease. The use of PT-Cy appears to be associated with improved outcomes and may at present represent the optimal transplant strategy in this pt population. Figure Disclosures Corradini: kite: Honoraria; Abbvie: Honoraria; Servier: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Roche: Honoraria; Novartis: Honoraria; KiowaKirin: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Ho:Jazz Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Consultancy; Omeros Corporation: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Kite: Consultancy, Other: advisory board, Research Funding; Novartis: Consultancy, Other: advisory board, Research Funding; Juno: Consultancy, Other: advisory board; Unum Therapeutics Inc.: Research Funding. Herrera:Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; AstraZeneca: Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding. Blaise:Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria. Hamadani:Pharmacyclics: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Merck: Research Funding; Otsuka: Research Funding; Janssen: Consultancy; Medimmune: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy. Ansell:LAM Therapeutics: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding. Nieto:Astra-Zeneca: Research Funding; Affimed: Consultancy; Affimed: Research Funding; Novartis: Research Funding. Feldman:Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Pfizer: Research Funding; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Portola Pharma: Research Funding; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Kyowa Hakko Kirin: Research Funding; Eisai: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Viracta: Research Funding; Trillium: Research Funding; Roche: Research Funding; Takeda: Honoraria, Speakers Bureau. McGuirk:ArticulateScience LLC: Other: Assistance with manuscript preparation; Bellicum Pharmaceuticals: Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gamida Cell: Research Funding; Pluristem Ltd: Research Funding; Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Stamatoulas Bastard:Celgene: Honoraria; Takeda: Consultancy. Houot:Bristol Myers Squibb: Honoraria; Merck Sharp Dohme: Honoraria. Manson:Bristol Myers Squibb: Honoraria. Orvain:Incyte: Honoraria; Novartis: Honoraria; Jazz Pharmaceuticals: Other: Travel & accommodations; Pfizer: Other: Travel & accommodations. Bouabdallah:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Frigault:Novartis: Consultancy; Kite/Gilead: Honoraria; Nkarta: Consultancy; Incyte: Consultancy; Juno/Celgene: Consultancy; Foundation Medicine: Consultancy; Xenetic: Consultancy. Chen:Takeda: Consultancy; Kiadis: Consultancy; Magenta: Consultancy; Abbvie: Consultancy; Incyte: Consultancy. Lynch:T.G. Therapeutics: Research Funding; Rhizen Pharmaceuticals S.A: Research Funding; Takeda Pharmaceuticals: Research Funding; Juno Therapeutics: Research Funding; Incyte Corporation: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy. Smith:AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp & Dohme Corp: Consultancy, Research Funding; Acerta Pharma BV: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Bristol-Myers Squibb (spouse): Research Funding; Denovo Biopharma: Research Funding; Genentech: Research Funding; Ignyta (spouse): Research Funding; Incyte Corporation: Research Funding; Ayala (spouse): Research Funding; Seattle Genetics: Research Funding. Byrne:Karyopharm: Research Funding. Cohen:Hutchison: Research Funding; Astra Zeneca: Research Funding; Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Genentech, Inc.: Consultancy, Research Funding; UNUM: Research Funding; ASH: Research Funding; LAM Therapeutics: Research Funding; Lymphoma Research Foundation: Research Funding. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Santoro:Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Takeda: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau; BMS: Consultancy; Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau. Armand:Sigma Tau: Research Funding; Otsuka: Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy; Tensha: Research Funding; Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Infinity: Consultancy; Genentech: Research Funding. Zinzani:Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Honoraria, Speakers Bureau. Carlo-Stella:Servier: Consultancy, Honoraria, Other: Travel, accommodations; Genenta Science srl: Consultancy; Boehringer Ingelheim: Consultancy; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Novartis: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Sanofi: Consultancy, Research Funding; Rhizen Pharmaceuticals: Research Funding; Celgene: Research Funding; Amgen: Honoraria; AstraZeneca: Honoraria; Janssen Oncology: Honoraria; MSD: Honoraria; BMS: Honoraria; Janssen: Other: Travel, accommodations; Takeda: Other: Travel, accommodations.
- Published
- 2019
7. The Treatment of Hairy Cell Leukemia with a Focus on Long Lasting Responders to Cladribine: A Thirty-Year Experience from the Institute of Hematology of Bologna
- Author
-
Lisa Argnani, Vittorio Stefoni, Alice Morigi, Pier Luigi Zinzani, Beatrice Casadei, Michele Cavo, Laura Nanni, Ginevra Lolli, Alessandro Broccoli, Miriam Marangon, Cinzia Pellegrini, Matteo Carella, and Carolina Terragna
- Subjects
Oncology ,Long lasting ,medicine.medical_specialty ,Hematology ,business.industry ,education ,Immunology ,Complete remission ,Cell Biology ,medicine.disease ,Biochemistry ,Internal medicine ,medicine ,Hairy cell leukemia ,business ,Cladribine ,health care economics and organizations ,medicine.drug - Abstract
The treatment of hairy cell leukemia (HCL) has deeply changed over years. Purine analogs, namely cladribine (2CdA) now represent the treatment of choice. The BRAF V600E mutation is now regarded as the pathogenic event. One hundred and eighty-four patients were followed between 1986 and 2018 and treated according to era-specific guidelines. This is the largest monocentric series reported. Responses were classified by combining Consensus Resolution criteria and marrow immunohistochemistry. Patients were grouped according to the number of treatment lines they received (table). Ten patients treated with frontline 2CdA and in complete response (CR) for at least 5 years were tested for the presence of the BRAF V600E mutation in peripheral blood by droplet digital PCR as a molecular marker for active disease. Patients treated first line responded in 86% of cases, with 44% CR. Response rates remained high throughout the first 4 lines (84%, 81%, 79% for the second line onward, with CR in 38%, 37%, 15% of cases respectively), although decreasing progressively with the number of treatments received. One hundred and twenty-two patients received 2CdA as first line treatment, with a response rate of 86% and a CR rate of 54%. Among the 66 CR patients, 45 (68%) have never received further therapy: 11 patients are in continuous CR between 5 and 10 years after treatment, 14 between 10 and 20 years and 3 patients at more than 20 years. Median time-to-next treatment (TTNT) for patients after receiving 2CdA was 8.2 years: partial responders had a significantly shorter median TTNT than CR patients (5.3 years versus median not reached at 25.8 years, p=0.0001) (figure). Seven patients in CR for more than 5 years after front line 2CdA were BRAF V6500E negative in peripheral blood. One of these displayed disease recurrence and required further treatment roughly 2 years later. Three patients were positive for the BRAF V600E mutation at 6.5, 8.4 and 13.7 years after treatment and developed an overt disease relapse between 4 months and 2 years. Patients with HCL require subsequent lines of therapy in more than 50% of cases. Purine analogs allow significant response rates when applied first line and upon retreatment. Some patients may enjoy long lasting responses after one course of 2CdA and display no evidence of BRAF V600E mutation in peripheral blood. A PCR-based evaluation of the allelic burden in peripheral blood may provide information regarding disease activity over time. Figure Disclosures Cavo: Celgene, Janssen, Amgen, BMS, Abbvie, Takeda: Honoraria; Janssen, Celgene: Other: Travel Accommodations; Janssen, Celgene: Speakers Bureau; Janssen, Celgene, Amgen, Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Zinzani:TG Therapeutics: Honoraria, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
- Published
- 2019
8. Phase II Study of the Fondazione Italiana Linfomi on Gemcitabine Plus Romidepsin (GEMRO Regimen) in Relapsed and Refractory Peripheral T-Cell Lymphoma Patients
- Author
-
Letizia Gandolfi, Pier Luigi Zinzani, Alessandro Broccoli, Paolo Corradini, Vittorio Stefoni, Lucia Farina, Enrico Derenzini, Annalisa Chiappella, Lorella Orsucci, Francesco Spina, Federico Monaco, Cinzia Pellegrini, Flavia Salvi, Lorenzo Tonialini, Umberto Vitolo, Anna Dodero, Marco Ladetto, Lisa Argnani, Federica Quirini, and Beatrice Casadei
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Phases of clinical research ,Salvage therapy ,Cell Biology ,Hematology ,Neutropenia ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Gemcitabine ,Surgery ,Romidepsin ,Regimen ,Internal medicine ,Clinical endpoint ,Medicine ,business ,medicine.drug - Abstract
Introduction. Relapsed and primary refractory peripheral T-cell lymphomas (PTCL) show a dismal outcome, with a 5-year overall survival of only 30%. There is no standard salvage chemotherapy for these patients. Gemcitabine was proved to be an effective monotherapy, yelding 60-70% overall response rates in patients with advanced heavily pre-treated disease. Romidepsin, a histone deacetylase inhibitor recently approved by Food and Drug Administration, has demonstrate an overall response rate (ORR) of 30% and a complete response (CR) rate of 16%. We have recently designed a multicentric trial to investigate the role of the combination of gemcitabine plus romidepsin (GEMRO regimen) in relapsed or refractory PTCL, looking for a potential synergistic effect of the two drugs. Methods. Twenty relapsed/refractory PTCL patients were included in a multicentric, prospective phase II trial which contemplated an induction with romidepsin 12 mg/m2 intravenously (i.v.) on days 1, 8, 15, and gemcitabine, 800 mg/m2 i.v. on day 1 and 15, for 6 cycles, each cycle to be repeated every 28 days. After the induction phase, patient who obtained at least a partial remission (PR) proceeded onto romidepsin maintenance at the dose of 14 mg/m2 i.v. until disease progression. The primary endpoint was to evaluate the efficacy of GEMRO regimen after the induction phase, as assessed by complete response (CR) rate; safety assessment was regarded as a secondary objective. The trial was registered under EudraCT (2012-001404-38). Results. Twenty patients have been recruited for this study. At present time, all patients underwent the induction phase and are evaluable for response and toxicity. The median age of patients was 55 years (range, 24-77). According to histology, 10 patients had PTCL not otherwise specified, 9 had an angioimmunoblastic T-cell lymphoma, 1 had a kinase negative anaplastic large cell lymphoma. The median number of prior therapies was 2 (range, 1-4); 7/20 (35%) patients had failed a prior stem cell transplant. Nineteen out of 20 (95%) patients presented with advanced stage. At the end of induction phase, the ORR was 31% including 2 CRs and 3 PRs. One of the 2 CR patients discontinued the treatment after 4 cycles due to cardiac toxicity, however maintaining a continuous CR with a follow up of 2 years. The other CR patient is still on treatment in maintenance phase. Grade ≥3 adverse events were represented by thrombocytopenia (60%), neutropenia (50%), and anemia (20%). Conclusions. To date, data failed to show a superiority of the GEMRO combination regimen over single agent romidepsin as salvage therapy for refractory or relapsed PTCL patients. More mature data and an adequate follow-up will be required to better understand the role of this combination regimen. Disclosures Zinzani: Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; J&J: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
- Published
- 2015
9. Long-Term Responders after Brentuximab Vedotin: Experience on 57 Patients with Relapsed and Refractory Hodgkin and Anaplastic Large Cell Lymphoma
- Author
-
Letizia Gandolfi, Vittorio Stefoni, Cinzia Pellegrini, Lorenzo Tonialini, Alessandro Broccoli, Pier Luigi Zinzani, Lisa Argnani, Federica Quirini, Enrico Derenzini, Michele Cavo, and Beatrice Casadei
- Subjects
medicine.medical_specialty ,CD30 ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Surgery ,Transplantation ,Refractory ,Median follow-up ,Internal medicine ,medicine ,business ,Brentuximab vedotin ,Anaplastic large-cell lymphoma ,Survival rate ,medicine.drug - Abstract
Brentuximab vedotin (BV) is an antibody drug-conjugate targeting CD30 linked to monomethyl auristatin E. Several studies have shown the efficacy of BV in patients with refractory or relapsed Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). We reviewed our clinical database to evaluate the long-term efficacy of this treatment. From July 2009 to February 2015, 57 patients were treated with BV in our Institute: 43 with a diagnosis of HL and 14 with sALCL. Thirty-six were males and 21 were females, with a median age of 33 years (range 16-77). All of them had been heavily pretreated before BV with a median number of previous therapies of 3 (range 2-10). Thirty-nine had refractory disease and 18 were relapsed. Autologous stem cells transplantation had failed in 30 patients. BV was administered at a dosage of 1.8 mg/mq, every 21 days, for a maximum of 16 cycles. The median number of cycles was 8 (range 2-16); 13 patients completed the entire schedule. The best overall response rate was globally 57,8% (33 of 57 patients), including 25 (43.8%) complete responses (CR): 18 with HL and 7 with sALCL. At present, 20/25 (80%) patients are still in continuous CR (CCR) with a median follow up of 9 months (range 3-41): 10 of them have consolidated the response with a stem cell transplantation (SCT) (4 auto-SCT and 6 allo-SCT) and 10 patients have remained in CR without any other therapy after BV. Among these long-term responders without any consolidation (7 patients with HL and 3 with sALCL), the median follow-up is 12 months (range 3-37); in particular there are 3 patients in CCR after at least 24 months. The global overall survival rate at 68 months is 71% (no patients with sALCL dead) and the median overall survival has not been reached yet. The global progression-free survival rate at 48 months is 30%, the median is achieved at 11,7 months. Toxicity was primarily neurological with peripheral sensory symptoms (30%) and motor neuropathy (5%); the majority was grade 3 in severity (8 patients). This study confirms the safety and the high efficacy of BV that can be considered an effective treatment in patients with relapsed or refractory HL or sALCL. This drug can induce a durable complete response representing a "bridge" to auto-SCT or allo-SCT. However our data show a subset of patients that can be considered "long-term responders", who have remained in CCR without any consolidation after BV. Disclosures Zinzani: Celgene: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Cavo:Janssen: Honoraria; Celgene: Honoraria, Speakers Bureau; Amgen: Honoraria; Bristol Myers Squibb: Honoraria; Novartis: Honoraria.
- Published
- 2015
10. The Treatment of Primary Mediastinal Large B-Cell Lymphoma: A Two Decades Monocentric Experience on 98 Patients
- Author
-
Enrico Derenzini, Beatrice Casadei, Pier Luigi Zinzani, Vittorio Stefoni, Cinzia Pellegrini, Lisa Argnani, Federica Quirini, Alessandro Broccoli, and Letizia Gandolfi
- Subjects
Vincristine ,medicine.medical_specialty ,Chemotherapy ,Dose-dense chemotherapy ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,CHOP ,Biochemistry ,Chemotherapy regimen ,Gastroenterology ,Surgery ,Regimen ,Internal medicine ,medicine ,Rituximab ,business ,Etoposide ,medicine.drug - Abstract
The first line treatment for primary mediastinal large B-cell lymphoma (PMLBCL) still remains a matter of debate even if the literature confirms that an anthracycline-containing regimen should be the main choice. The European experience shows the superiority of “third-generation” dose-dense regimen like MACOP-B (methotrexate, doxurubicin, cyclophosphamide, vincristine, bleomycin, prednisone) or VACOP-B (same as MACOP-B, with etoposide instead of methotrexate) over CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) or CHOP-like regimen. The addition of rituximab to third-generation regimen does not seem to cause any advantages in terms of overall survival (OS) and progression free-survival (PFS), while external radiotherapy (RT) has shown a good efficacy as a consolidation strategy at the end of induction chemotherapy, especially in converting partial responses (PR) into complete responses (CR). Between October 1989 and April 2010, 98 (58 females and 40 males) previously untreated PMLBCL patients were diagnosed and subsequently treated at our Institution. All patients were treated with MACOP-B regimen, concurrent rituximab was administered in 57 patients (58.2%) and 67 patients (68.4%) received mediastinal RT. Among 57 patients who received rituximab, 37 (64.9%) underwent RT whereas, among 41 who did not receive rituximab, RT was delivered in 30 (group 4, 73.2%) patients. 11 patients (group 1, 11.2%) received chemotherapy alone and 37 (group 3, 37.8%) received besides immunotherapy and RT (Table 1). All patients were assessed at the diagnosis and after the treatment with computed tomography and positron emission tomography (after 2001) scan. Main aims of our study were the effectiveness of the regimen measured as overall response rate (ORR) and patients survival. Sixty-one (62.2%) out of 98 patients achieved a CR and 27 (27.6%) were in PR after 12 cycles of MACOP-B regimen (with or without rituximab). Twenty-one patients in PR after (immuno)chemotherapy converted the response into CR with mediastinal RT. At the end of the scheduled treatment, 82 patients (83.7%) achieved a CR and 6 a PR (6.1%), yielding an ORR of 89.8%. At a median follow-up of 5.6 years, 9 patients relapsed within the first 2 years of treatment. During the follow-up 15 patients died, of whom 13 as a consequence of disease relapse or progression . The projected OS at 17 years is 72% with a PFS and a disease free survival (DSF) of 86.8% and 88.4% respectively ([Figure 1][1] A-C). The subgroup analysis shows a statistically significant difference in term of OS (p=0.0003) but not in term of PSF and DFS among the four groups of treatment ([Figure 1][1] D-F). All the patients receiving consolidation RT obtained a CR without differences between subgroup 3 and 4. RT seems to have a small consolidative potential in patients who obtained CR after chemo-immunotherapy alone: there are no differences in term of DFS between subgroup 2 and 3. No statistically significant differences in terms of OS, PFS and DSF occurred among patients received rituximab or not, regardless of a subsequent RT. Our monocentric experience spans a period of 20 years and indicates that a third-generation regimen like MACOP-B is feasible and could be a standard of first line treatment for PMLBCL. In agreement with the literature, adding rituximab doesn’t improve the outcome. Mediastinal RT, delivered as a consolidative strategy, impacts on global survival and on CR rates. In particular, RT after third-generation regimen remains a good strategy to convert PR into CR, but it may be avoided in patients obtaining CR after (immuno)chemotherapy. | Group | MACOP-B | Rituximab | Radiotherapy | N (%) | | ----------- | --------- | ---------- | ------------ | ---------- | | 1 | Yes | No | No | 11 (11.2%) | | 2 | Yes | Yes | No | 20 (20.4%) | | 3 | Yes | Yes | Yes | 37 (37.8%) | | 4 | Yes | No | Yes | 30 (30.6%) | | TOTAL N (%) | 98 (100%) | 57 (58.2%) | 67 (68.4%) | 98 (100%) | Table 1 ![Figure 1][2] Figure 1 Disclosures No relevant conflicts of interest to declare. [1]: #F1 [2]: pending:yes
- Published
- 2014
11. Langerhans Cell Histiocytosis: A Single Institution Retrospective Analysis of Eleven Patients
- Author
-
Enrico Derenzini, Alessandro Broccoli, Lisa Argnani, Federica Quirini, Vittorio Stefoni, Beatrice Casadei, Letizia Gandolfi, Pier Luigi Zinzani, and Cinzia Pellegrini
- Subjects
medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Gastroenterology ,Surgery ,Radiation therapy ,Regimen ,Autologous stem-cell transplantation ,Langerhans cell histiocytosis ,B symptoms ,Eosinophilic granuloma ,Internal medicine ,Medicine ,medicine.symptom ,business - Abstract
Langerhans cell histiocytosis (LCH), is a rare disorder which has a substantially unknown etiology, pathophysiology, and may manifest through a variety of clinical presentations ranging from solitary eosinophilic granuloma to severe multisystem disease. LCH is more common in children, although it can affect any age; the most common sites of involvement are bone, skin, and lung. From a histological point of view LCH derives from accumulation of proliferating cells with surface markers and ultrastructural features similar to cutaneous Langerhans cells, intermixed with inflammatory cells, particularly eosinophils. Below, a retrospective analysis of LCH patients treated at our institution. Between 1997 and 2013 we have treated 11 LCH patients, including 6 females and 5 males with a median age at time of diagnosis of 42.9 years (range 22.2-62.3). All diagnoses were reviewed by our pathologist. With regard to the site at onset, 9 patients had bone involvment, among these, four patients had only bone involvment, the other five patients also lung, oral cavity and lymph nodes. At time of onset 4 patients showed no symptoms, while the remaining 7 showed a variety of symptoms ranging from B symptoms to tinnitus, dizziness, and other neurological symptoms such as diplopia. Among the study group 6 patients had multisystemic involvement. All patients except one had CT scan performed before, during, and at follow-up, the remaining patient was studied and followed through follow-up with PET scan. As first-line therapy 8 patients underwent chemotherapy, 2 patients radiation therapy, 1 patient required only steroid therapy. The most frequently used chemotherapy regimen for these 8 patients was MACOP-B, a third generation, CHOP-like regimen. Responses to first-line therapy were as follows: 7 complete remissions (CR), resulting with chemotherapy (5), radiation therapy and steroid therapy, two partial remissions (both obtained with chemotherapy) and two stable diseases (1 with chemotherapy and 1 with radiation therapy). Two patients relapsed, of whom one has ran several lines of chemotherapy, including autologous stem cell transplantation. Both are alive at the time of the last follow-up. To date all patients are alive but one, who died of pulmonary embolism while he was in stable disease. Six patients are in CR (60%), two in SD (20%) and two in PD (20%). In conclusion, our monocentric experience of 11 LCH patients confirms what reported in the literature in terms of heterogeneity of presentation, age, sites of involvement, symptomatology and treatment demanded. Coming to the the results our retrospective analisys shows that ten of the eleven study population patients (90.9%) are to date still alive after a significant median time of follow-up; six out of these ten patients (60%) are in CR. Disclosures No relevant conflicts of interest to declare.
- Published
- 2014
12. Efficacy and Safety of Biosimilar Epoetin Alpha in Patients with Chronic Lymphoproliferative Syndromes and Chemotherapy-Induced Anemia: An Observational, Retrospective, Monocentric Analysis
- Author
-
Enrico Derenzini, Lisa Argnani, Alessandro Broccoli, Federica Quirini, Pier Luigi Zinzani, Cinzia Pellegrini, Letizia Gandolfi, Vittorio Stefoni, and Beatrice Casadei
- Subjects
Bendamustine ,medicine.medical_specialty ,Chemotherapy ,Anemia ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,CHOP ,medicine.disease ,Biochemistry ,Gastroenterology ,Chemotherapy regimen ,Surgery ,Fludarabine ,Regimen ,Erythropoietin ,Internal medicine ,medicine ,business ,medicine.drug - Abstract
INTRODUCTION. Chemotherapy (CHT)-induced anemia is a consequence of the myelosuppressive effect of CHT, delivered for solid or hematologic malignancies, and tends to worsen over the course of repeated cycles of therapy. Erythropoietic agents have shown their efficacy in correcting CHT-induced anemia in cancer patients, in reducing the need of blood transfusion and in improving patients’ quality of life. Epoetin (EPO) biosimilars have emerged as an alternative to originator products, sharing an equivalent mechanism of action, efficacy and safety, as a result of a rigorously conducted comparability exercise. PATIENTS AND METHODS. This study was aimed at evaluating the response to EPO alpha biosimilar (Binocrit®, Sandoz, 40,000 IU/week subcutaneously) after a 4-weeks (and 8-weeks, when applicable) treatment period, as well as the rate of CHT cycles delays or interruptions due to anemia, in 49 consecutive adult patients, affected by chronic lymphoproliferative disorders, undergoing CHT, either as a first-line induction (35 patients) or second-line or salvage treatment (14 patients), and presenting with CHT-induced anemia. The median age was 69 (range 21-90) years, with 49% of the patients older than 70. Fourteen had diffuse large B-cell lymphoma, 14 an indolent non-Hodgkin’s lymphoma, 6 had chronic lymphocytic leukemia, 5 mantle cell lymphoma, 4 T-cell lymphoma, 2 hairy cell leukemia and 1 had histiocytosis. Response to EPO was defined as an increase in hemoglobin (Hb) levels after 4 (ΔHb4) and 8 weeks (ΔHb8) of treatment of at least +1 g/dL, or as the achievement of Hb > 11 g/dL independently of ΔHb, with a complete transfusion-independence. Hb stability was regarded as a ΔHb comprised between -1 and +1 g/dL. A ΔHb < -1 g/dL or an acquired transfusion dependence was judged as a lack of response. Treatment with EPO was started at the first occurrence of Hb < 10 g/dL during chemotherapy, when anemia was not due to any different concomitant cause (e.g. hemolysis, iron deficiency, malabsorption, etc). Treatment duration was established by the treating physician; however, treatment was stopped when Hb reached at least 11 g/dL, in patients whose chemotherapy programme had reached its completion and in those who became transfusion dependent. RESULTS. Mean Hb (± standard deviation) at presentation was 11.0 ± 1.6 g/dL, with 49% of patients being anemic mostly as a consequence of their disease. Nine patients had grade 2 anemia, while one presented with grade 3 anemia. Twenty-one were treated with a cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) every 21 days or with a weekly CHOP-like regimen; 10 received a fludarabine-based regimen; 6 underwent a bendamustine-based second-line treatment. The remaining 12 patients were treated with various regimens (lenalidomide, rituximab, cladribine, temsirolimus, gemcitabine). Mean Hb level at EPO treatment start was 9.3 ± 0.5 g/dL. After 4 weeks of treatment, the reached mean Hb level was 10.8 ± 1.4 g/dL for patients receiving a first-line CHT, and 11.4 ± 1.6 g/dL for those on a second or later CHT line, with a mean ΔHb4 of 1.4 ± 1.4 g/dL and 2.1 ± 1.6 g/dL for each group of patients, respectively. Sixteen patients had their Hb level measured after 8 weeks of treatment, achieving a mean Hb level of 11.0 ± 1.7 g/dL and 9.8 ± 1.4 g/dL for each treatment subgroup, with a ΔHb8 of 1.7 ± 1.6 g/dL and 0.5 ± 1.3 g/dL, respectively. Overall, 36 patients responded to the treatment, yielding to a 73.4% hematological improvement rate. Eleven patients (22.5%) showed a stable Hb level throughout their treatment course, and 2 (4.1%) were considered non-responders (figure). Among responders, 2 patients required a new biosimilar EPO alpha treatment, again with response; 2 patients showed a late recurrence of anemia, and were managed with blood transfusions. Overall, 22 patients (44.9%; 61.1% of responders) had an Hb increase of at least 2 g/dL. CHT cycles were delayed in 9 cases (18.4%) because of anemia; interruptions of the planned CHT programme occurred in 6 cases (12.2%). No adverse events were documented; in particular, no thromboembolic or pure red-cell aplasia episodes have been demonstrated. CONCLUSION. The treatment of CHT-induced anemia with biosimilar EPO alpha in patient with chronic lymphoproliferative disorders is correlated with a high rate of responses and allows a safe completion of the planned CHT programme in most of the cases, both in induction and salvage treatment settings. Figure 1 Figure 1. Disclosures Broccoli: Sandoz: Membership on an entity's Board of Directors or advisory committees. Zinzani:Sandoz: Membership on an entity's Board of Directors or advisory committees.
- Published
- 2014
13. Genomic Instability and Activation Of The DNA Damage Response Pathway Is An Independent Predictor Of Poor Prognosis, Is Associated With MYC Expression and Is a Promising Target For Therapy In Diffuse Large B Cell Lymphoma
- Author
-
Claudio Agostinelli, Ilaria Iacobucci, Stefano Pileri, Enrica Imbrogno, Enrico Derenzini, Giovanni Martinelli, Pier Luigi Zinzani, and Beatrice Casadei
- Subjects
Genome instability ,Oncogene ,Kinase ,DNA damage ,Immunology ,Germinal center ,Cell Biology ,Hematology ,Biology ,medicine.disease ,Biochemistry ,Molecular biology ,chemistry.chemical_compound ,chemistry ,Apoptosis ,hemic and lymphatic diseases ,medicine ,Cancer research ,Propidium iodide ,Diffuse large B-cell lymphoma - Abstract
Introduction Genomic instability and constitutive activation of the DNA damage response (DDR) pathway has been recently described in models of aggressive myc-driven lymphoid malignancies. The MYC oncogene has been reported to induce genomic instability by a mechanism involving replication stress. On the other hand, MYC is overexpressed in a fraction of diffuse large B-cell lymphomas (DLBCLs), and its overexpression has been reported to be associated with poor prognosis. The checkpoint kinases 1 (CHK1) and 2 (CHK2), are serine-threonine kinase involved in the DDR pathway. DDR activation triggers the phosphorylation of the histone H2AX at ser 139, a known marker of DNA damage and genomic instability. The correlation between genomic instability, MYC expression, and prognosis has not been investigated yet in DLBCL. Methods Immunohistochemistry (IHC) for phospho (γ) H2AX, pCHK1, pCHK2 was performed in tissue microarrays (TMAs) from 97 consecutive patients treated at our Institution between 2004 and 2011 with R-CHOP/CHOP-like regimens, with available paraffin embedded tissue from initial diagnosis. Moreover, to evaluate the therapeutic potential of DDR pathway inhibition in DLBCL, the DLBCL cell lines HBL-1, U2932, TMD8, SUDHL-6, BJAB, SUDHL-4 and primary DLBCL cells were incubated with the CHK inhibitor PF-0477736 (Pfizer). Results In the TMA study 57% of patients (n=55) displayed high levels of basal γH2AX (>30% of positive cells), 55% (n=53) displayed pCHK1/pCHK2 activation and of note all DLBCL cell lines showed detectable baseline activation of CHK1/CHK2 and/or H2AX phosphorylation, by western immunoblotting. γH2AX positive cases distributed equally in germinal center (GC) and in non GC DLBCLs, and were significantly associated with MYC expression (p Conclusions A significant fraction of DLBCLs shows high levels of inherent genomic instability; the DDR activation marker γH2AX is a poor prognostic predictor in DLBCL and interestingly is significantly associated with MYC expression. DDR inhibition resulted to be highly effective in DLBCL cell lines and primary DLBCL cells; on treatment modifications of CHK1 and H2AX phosphorylation could be useful biomarkers of CHK inhibitors activity. These data provide strong rationale for targeting the DDR pathway and for clinical investigation of CHK inhibitors in DLBCL. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2013
14. Sequential R-CHOP and R-FM Chemotherapy Followed By Autologous Stem Cell Transplantation Results In High Rates Of Long Term Remission In Advanced Follicular Lymphoma
- Author
-
Vittorio Stefoni, Letizia Gandolfi, Beatrice Casadei, Giulia Stefani, Stefano Fanti, Pier Luigi Zinzani, Lisa Argnani, Cinzia Pellegrini, Enrico Derenzini, and Alessandro Broccoli
- Subjects
Oncology ,Melphalan ,medicine.medical_specialty ,business.industry ,Immunology ,Follicular lymphoma ,Cell Biology ,Hematology ,CHOP ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Surgery ,Fludarabine ,Autologous stem-cell transplantation ,Internal medicine ,medicine ,Rituximab ,Progression-free survival ,business ,medicine.drug - Abstract
Introduction Autologous stem cell transplantation (ASCT) is a potentially curative treatment option for relapsed Follicular Lymphoma (FL) patients, but to date available data do not support the use of ASCT as first line consolidation, given the lack of overall survival (OS) advantage compared to standard therapy. R-CHOP (Rituximab-Cyclophosphamide, Vincristine, Doxorubicin, Prednisone) and R-FM (Rituximab, Fludarabine, Mitoxantrone), have comparable efficacy and are widely used as first and second line combinations. The best way to sequence the available therapies in FL is still undefined. Here we show the long term results of a phase II trial of sequential chemotherapy alternating CHOP and FM plus Rituximab followed by ASCT in patients with stage III-IV and/or bulky FL either at disease onset or first relapse, conducted in our Institution from 2002 to 2008. Methods Patients at diagnosis or first relapse were treated in sequence with R-CHOP for 4 cycles, Endoxan 7g/m2 followed by hematopoietic stem cell harvest, R-FM for 4 cycles and ASCT. The ASCT conditioning schedule was BEAM (BCNU, ARA-C, Etoposide, Melphalan) in all cases. Results 24 patients were enrolled, 12 pts were male. Median age was 44 years. One patient did not undergo ASCT for insufficient left ventricular ejection fraction and was excluded from the analysis. 13 patients were treated upfront whereas 10 patients at first relapse. After a median follow-up of 10 years, progression free survival (PFS) and OS in the whole study cohort were respectively 65% and 87%, with a complete response (CR) rate after the completion of sequential treatment of 100%. PFS and OS for patients treated at disease relapse were 60 and 70% (4 relapses, 3 deaths). Remarkably PFS and OS for the 13 patients treated upfront was 70% and 100% (4 relapses). To date no secondary malignancies were observed. Conclusions Sequential treatment alternating standard R-CHOP and R-FM followed by ASCT results in impressive long term PFS and OS rates, both in first line and at relapse. These data represent the proof of principle of a sequential therapy containing alternating alkylating agents and purine analogs followed by ASCT in FL. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2013
15. Primary Mediastinal Large B-Cell Lymphoma: Investigation On The Role Of Rituximab and PET During Treatment
- Author
-
Pier Luigi Zinzani, Beatrice Casadei, Enrico Derenzini, Cinzia Pellegrini, Lisa Argnani, Federica Quirini, Vittorio Stefoni, Alessandro Broccoli, and Letizia Gandolfi
- Subjects
medicine.medical_specialty ,Vincristine ,business.industry ,medicine.medical_treatment ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,Biochemistry ,Surgery ,Radiation therapy ,Regimen ,Prednisone ,medicine ,Rituximab ,Radiology ,Stage (cooking) ,Prospective cohort study ,business ,medicine.drug - Abstract
Due to limited prospective studies, the optimal treatment of primary mediastinal large B-cell lymphoma (PMLBCL) is still a matter of debate. Third-generation MACOP-B (adriamycin, cyclophosphamide, vincristine, bleomycin, methotrexate and prednisone) regimen in combination with mediastinal radiotherapy (RT) seems to improve disease free survival of patients. In addition, the impact of additional treatment with rituximab and the role of PET are still under investigation due to controversial reported results. As per institutional guidelines, MACOP-B plus RT was recommended in all PMLBCL patients until 2002. Aim of this report was evaluate the outcome of PMBCL patients diagnosed and treated with MACOP-B plus rituximab and consolidative mediastinal RT (30-36 Gy) after 2002. PET role was also investigated. Seventy-four patients were deemed eligible for this study (follow up of at least 2 years). Fifty patients had stage II and 24 stage IIE-IV, bulky disease was documented in 93% of patients. Median age was 34 years (range, 17-62) and 59.5% were females. All patients were evaluated by both CT and PET scan. After the final PET evaluation, PET-negative patients were observed while PET-positive patients underwent mediastinal RT. At the end of treatment, 61 (82.4%) patients achieved a complete response (CR); 51 (68.9%) presented a positive final PET and were treated with local RT, while the other 23 (31.1%) had a negative PET. Five patients relapsed within 12 months. At 10 years, estimated overall survival was 82%, progression-free survival was 87.6% and disease-free survival (DFS) for the 61 CR patients was 90.5% (median follow-up 4 years). Regarding the DFS curve (figure 1), no statistically significant differences were observed between patients who underwent also RT (PET-positive, group 1) and patients who remained under observation (PET-negative, group 2): 90.7% (4/51 relapses) vs 90% (1/23 relapse) (p= 0.85), respectively. Comparing these results with our institutional historical series when the front-line for PMLBCL patients included only MACOP-B plus RT without any decision related to PET results (before 2002), the 10-year DFS resulted lower, i.e. 82.8%. Although with the limitations of an observational retrospective study, the present report underlines that the additional treatment with rituximab does not change the final results in terms of CRs and DFS utilizing third-generation regimens. Moreover, the introduction of the PET-guided RT approach after MACOP-B plus rituximab allows a patient tailored strategy which reduces the use of RT and preserves clinical outcomes. Figure 1 Figure 1. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2013
16. Collection of Hematopoietic Stem Cells After Previous Exposure to Ittrium-90 Ibritumumab Tiuxetan (Zevalin) Is Feasible and Does Not Impair Autologous Stem Cell Transplantation Outcome in Follicular Lymphoma
- Author
-
Roberto Maglie, Pier Luigi Zinzani, Cinzia Pellegrini, Stefano Fanti, Alessandro Broccoli, Lisa Argnani, Federica Quirini, Letizia Gandolfi, Maria Rosa Motta, Vittorio Stefoni, Michele Baccarani, Enrico Derenzini, and Beatrice Casadei
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Plerixafor ,Immunology ,Follicular lymphoma ,Ibritumomab tiuxetan ,Cell Biology ,Hematology ,CHOP ,medicine.disease ,Biochemistry ,Granulocyte colony-stimulating factor ,Fludarabine ,Autologous stem-cell transplantation ,Internal medicine ,Medicine ,business ,Hematopoietic Stem Cell Mobilization ,medicine.drug - Abstract
Abstract 3019 Background: Radioimmunotherapy (RIT) is an effective and manageable treatment option for those patients (pts) affected by follicular B-cell lymphoma (FL) who experience disease relapse. The results of RIT in the setting of first line consolidation are also very promising in terms of progression free and overall survival. On the other hand autologous stem cell transplantation (ASCT) is a suitable treatment option for relapsed FL patients. Although major concerns about the widespread use of RIT early in the disease course are the long term hematologic toxicity and the theoretical possible irreparable damage to bone marrow function with impairment of peripheral stem cell harvest, very few data are available about mobilization rates after Zevalin exposure. Methods: The aim of this monocentric study was to analyze the impact of prior Zevalin administration on peripheral blood stem cells (PBSC) mobilization and on the outcome of subsequent ASCT. Moreover the impact of different prior treatment regimens [Cyclophosphamide, Doxorubicin, Vincristine, Prednisone plus Rituximab (R-CHOP) or CHOP-like regimens vs Fludarabine, Mitoxantrone plus Rituximab (FM-R) vs Zevalin] and number of previous lines of therapy given earlier in the disease course, was prospectively evaluated in all FL patients (n=100) who underwent stem cell mobilization from January 2005 to March 2012. Results: At the time of mobilization, 68 pts had received R-CHOP or CHOP-like regimens, 20 pts FM-R, 12 pts RIT with Zevalin earlier in the disease course. Characteristics of pts such as age, weight and number of prior therapies, were well balanced in the 3 groups. Sixty one pts had received one prior therapy, 31 pts 2 therapies, 8 pts ≥ 3 lines of therapy. All pts received chemotherapy plus granulocyte colony stimulating factor (G-CSF) 5 μg/kg (n=94) or G-CSF alone (10 μg/kg) (n=6) as mobilization regimen. Mean CD34+ cells yield was 8.9 × 106/kg in the CHOP group, vs 5.8 × 106 CD34 + cells/kg in the FM-R group, vs 2.7 × 106 CD34 + cells/kg in the Zevalin group (p=0.05 CHOP vs FM-R; p 1000/μL) and platelets recovery (>20000/μL) was 10 and 11 days in all groups respectively. Only one pt in the CHOP group and one in the FM-R group did not undergo ASCT because of insufficient CD34+ harvest. Considering the Zevalin group (n=12), median age was 51 years (range 36–66). Seven pts received Zevalin as first line consolidation, 5 patients at disease relapse. Median number of prior therapies was 2 (range 1–4). Ten pts received chemotherapy plus G-CSF as initial mobilization regimen, 2 pts received G-CSF alone. Median time from RIT to mobilization was 13 months (4–60 months). Five pts (42%) reached the collection yield of > 2.0 × 106 CD34 + cells/kg with the first mobilization attempt. Considering the remaining 7 pts who failed (CD34+ cells below 10/mL before apheresis, or cell harvest below 2.0 × 106 CD34 + cells/kg), a surgical procedure was attempted in 4 pts, G-CSF + Plerixafor (240 μg/kg) in 3 pts. Remarkably the second harvest allowed 5 additional pts (3 pts after surgery, 2 pts after G-CSF + Plerixafor) to undergo ASCT. Finally ASCT was succesfully performed in 9 pts (75%). Median number of reinfused CD34+ cells was 2.3 × 106 CD34 + cells/kg (0.4–4.2). Three pts did not undergo ASCT, one because of disease progression, 2 pts because of insufficient CD34+ harvest. Conclusions: The type of previous therapy may significantly influence the mobilization rate in FL pts. Although mobilization was significantly impaired in pts previously treated with Zevalin compared to other chemotherapy regimens, stem cell harvest after RIT was feasible and the vast majority of patients retained the possibility to undergo ASCT with a second stem cell harvest, with no significant impact on engraftment. The use of Plerixafor seems to be particularly promising for those patients previously exposed to RIT who failed the first mobilization. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2012
17. Fludarabine, Mitoxantrone and Rituximab (FMR) Regimen in Previously Untreated Patients with Indolent Non-Hodgkin Lymphoma: Efficacy, Safety and PET Data On 285 Patients
- Author
-
Lisa Argnani, Federica Quirini, Enrico Derenzini, Pier Luigi Zinzani, Letizia Gandolfi, Beatrice Casadei, Cinzia Pellegrini, Vittorio Stefoni, and Alessandro Broccoli
- Subjects
medicine.medical_specialty ,Mitoxantrone ,business.industry ,Immunology ,Follicular lymphoma ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Fludarabine ,Surgery ,Median follow-up ,Internal medicine ,Indolent Non-Hodgkin Lymphoma ,medicine ,Outpatient clinic ,Rituximab ,Marginal zone B-cell lymphoma ,business ,medicine.drug - Abstract
Abstract 2736 In this retrospective single-center study we aimed at evaluating the efficacy and safety of fludarabine, mitoxantrone and rituximab (FMR) regimen as first line therapy in untreated patients with follicular non-Hodgkin lymphoma (NHL) and indolent non-follicular NHL considering also the role of positron emission tomography (PET) after this chemo-immunotherapy induction as predictor of survival. Between January 2000 and May 2011, 285 patients with stage II-IV untreated indolent follicular (excluding grade IIIb) NHL (n=142) and indolent non-follicular (including marginal zone lymphoma, MZL [n=111] and small lymphocytic lymphoma, SLL [n=31]) NHL (n=143) were diagnosed and treated at our institution in the outpatient clinic. Median age was 63 years (range, 25–83 years) and the median time from diagnosis to study entry was 3 months (range, 1–5 months). 20 patients had stage II, 75 patients had stage III, and 190 had stage IV disease (155 patients had bone marrow involvement). Standard fludarabine (25 mg/m2 iv on days 2, 3 and 4), mitoxantrone (10 mg/m2 iv on day 2) and rituximab (375 mg/m2 iv on day 1) were given every 28 days for six cycles. Globally, after FMR regimen, the overall response rate (ORR) was 83.2%, including a 71.6% complete remission (CR) rate (204 patients) and a 11.6% partial remission (PR) rate (33 patients). According to the histology, in the follicular subset, the ORR was 81.1% with a CR rate of 69.2% while in the indolent non-follicular subset the ORR was 85.2% with a CR rate of 73.9%. In particular, in the indolent non-follicular NHL subgroup the CR rate was 80.2% in MZLs and 51.6% in SLLs, respectively. Toxicities were generally mild and mainly hematologic. Overall 88 (30.8%) patients had grade ≥3 hematologic toxicity, and 26 (9.1%) patients had non-hematologic toxicity with 3 cases of grade ≥3 (1 neurologic toxicity and 2 hepatic toxicity). In terms of secondary malignancies, only 3 (1.0%) hematologic neoplasms were reported (1 myelodisplastic syndrome after 9 months from the end of the treatment and 2 acute lymphoblastic leukemia after 8 and 11 months from the end of the treatment, respectively). Globally with a median follow up of 40 months (range, 12–144 months), at 11 years the overall survival (OS) was 78.8%, the disease-free survival (DFS) was 73.4% (with only 29 relapses), and the progression-free survival (PFS) was 71.9%. Regarding the comparison between the two subsets, follicular vs indolent non-follicular, no statistically significant differences were observed in OS, DFS and PFS curves. Furthermore, a sub-sample of 132 patients (75 follicular NHLs and 57 indolent non-follicular NHLs) had a PET evaluation before the treatment (staging) and 4 to 6 weeks after completion of the sixth cycle of chemo-immunotherapy (restaging, final PET [f-PET]). Post-induction PET-positive patients had a significantly inferior OS at 6 years: 71.4% compared with 98.4% for f-PET-negative patients (p Figure 1a. Figure 1a. Figure 1b. Figure 1b. In conclusion, this study suggests and confirms that FMR is a very active, well tolerated (in terms of acute and long-term side effects) chemo-immunotherapy front-line treatment for follicular NHL and indolent non-follicular NHL. PET status at the end of this chemo-immunotherapy induction is quite controversial as a predictor of survival. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2012
18. The Role of Interim-PET and Final-PET in the Outcome of Peripheral T-Cell Lymphoma (PTCL) Treated At the Diagnosis with CHOP
- Author
-
Lisa Argnani, Federica Quirini, Beatrice Casadei, Cinzia Pellegrini, Alessandro Broccoli, Letizia Gandolfi, Vittorio Stefoni, Enrico Derenzini, and Pier Luigi Zinzani
- Subjects
End of therapy ,business.industry ,Immunology ,Cell Biology ,Hematology ,CHOP ,medicine.disease ,Biochemistry ,Interim pet ,Peripheral T-cell lymphoma ,Lymphoma ,medicine ,Stage (cooking) ,Nuclear medicine ,business ,Prospective cohort study ,Extranodal Involvement - Abstract
Abstract 2721 Role of interim- and final-PET in peripheral T-cell lymphoma (PTCL) is quite unknown. To determine predictive value of PET on overall survival (OS), we evaluated interim-PET (i-PET) and final-PET (f-PET) in PTCL patients treated in first-line with 6 CHOP-21 courses. From September 2003 to July 2010 we diagnosed and treated in our institution 34 advanced stage PTCL patients (15 females and 19 males). The median age at diagnosis was 46 years (range, 21–81 years); 9 patients were in stage III, and 25 in stage IV. According to the histologic subtype there were 11 PTCL-nos, 6 AILT, 9 ALCL Alk+, 6 ALCL Alk-, and 2 NK/T nasal type patients. Four patients had bulky disease; eight patients had bone marrow involvement, 15 patients had 1 extranodal involvement and 10 had more than 2 extranodal sites. All patients underwent initial staging PET/CT; i-PET was performed after 3 cycles of CHOP-21 and the median time from the end of third course to i-PET was 14 days (range, 7– 18 days). f-PET scans were performed 35 days (range, 30– 45 days) after the end of therapy. The table summarizes the correspondence between i-PET and f-PET results: N=34 f-PET negative, n (%) f-PET positive, n (%) i-PET negative 27 19 (70.4) 8 (29.6) i-PET positive 7 1 (14.2) 6 (85.8) With a median follow-up of 71 months (range, 5.8–120.9 months), 17/19 (89.5%) patients with i-PET negative are in continuous CR (CCR) and only 1/7 (14.2%) patient with i-PET positive is still in CCR. Figures show the overall survival (OS) according to response at i-PET and f-PET. In figure 1a we observe OS plotted according to i-PET results: 78.6% for negative patients (solid line) and 21.4% for positive patients (dashed line) at 88.7 months (p=0.02); in figure 1b we observe OS plotted according to f-PET results: 93.7% for negative patients (solid line) and 21.4% for positive patients (dashed line) (p In conclusion, our results demonstrate that positive i-PET is not predictive of a worse outcome in PTCL. On the contrary, the f-PET seems to represent a significant step forward in the prediction of survival for these patients. Larger and prospective studies and harmonization of PET reading criteria are needed. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2012
19. Fludarabine and Mitoxantrone Followed by Yttrium-90 Ibritumumab Tiuxetan in Untreated Patients with Follicular Lymphoma. Long Term Efficacy and Toxicity Results of the FLUMIZ Trial
- Author
-
Alessandro Pulsoni, Beatrice Casadei, Maria Teresa Voso, Enrico Derenzini, Cinzia Pellegrini, Alessandro Broccoli, Alfonso Zaccaria, Alberto Fabbri, Maria Giuseppina Cabras, Michele Baccarani, Marco Gobbi, Alessio Perrotti, Luigi Rigacci, Amalia De Renzo, Pier Luigi Zinzani, Vittorio Stefoni, Lisa Argnani, Federica Quirini, and Letizia Gandolfi
- Subjects
Oncology ,Mitoxantrone ,medicine.medical_specialty ,business.industry ,Immunology ,Ibritumomab tiuxetan ,Follicular lymphoma ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Surgery ,Fludarabine ,Regimen ,Chemoimmunotherapy ,Internal medicine ,medicine ,Progression-free survival ,business ,medicine.drug - Abstract
Abstract 1604 We previously reported the results of a multicenter non-randomized phase II trial of fludarabine and mitoxantrone plus radioimmunotherapy (RIT) [FLUMIZ (Fludarabine, Mitoxantrone, Zevalin) trial], demonstrating that this combination was safe and very effective in untreated patients with follicular non-Hodgkin lymphoma. We are now providing long term efficacy and toxicity results of this combination strategy. Sixty-one patients with stage III and IV untreated follicular lymphoma were enrolled between June 2004 and April 2006, at 13 Italian institutions. Briefly, treatment schedule was the following: oral fludarabine 40 mg/m2 on days 1–3, intravenous mitoxantrone 10 mg/m2 on day 1 every 28 days for six cycles, followed by one course of yttrium-90 (90Y)-labelled ibritumumab tiuxetan (Zevalin), which consisted in two weekly infusions of Rituximab 250 mg/m2 followed by a weight based dose of 90Y-ibritumumab tiuxetan. Primary endpoints at the time of the first analysis were complete response and hematological toxic effects, secondary endpoints were overall survival (OS) and progression free survival (PFS). Fifty-seven patients were treated with RIT after the completion of six courses of fludarabine and mitoxantrone (FN) regimen. Four patients were excluded because of disease progression (n=1) and bone marrow infiltration > 25% (n=3) at the end of the FN regimen. Median follow up at the time of the last analysis was 52 months (range 24–75). Five-year PFS was estimated to be 68%, 5-year OS was estimated to be 93.0%. Noteworthy, late hematological side effects such as myelodisplastic syndromes or acute myeloid leukemias have not been observed so far. All patients had a complete hematological recovery after the completion of the sequential treatment. 16 patients relapsed during the follow-up period and 4 patients died due to disease progression. 22 patients (38%) are in first complete remission after more than 4 years of follow-up. All relapsed patients underwent second line chemotherapy and high dose chemotherapy with stem cell rescue was performed in 4 patients. These results confirm the long term efficacy and safety of 6 cycles of fludarabine and mitoxantrone followed by consolidation with 90Y-ibritumumab tiuxetan: the 5-year PFS and OS compare favourably with the results of chemoimmunotherapy alone in untreated follicular lymphoma, with no increased incidence of secondary hematologic malignancie Disclosures: No relevant conflicts of interest to declare.
- Published
- 2011
20. Adoptive Immunotherapy with Haploidentical Kir Ligand-Mismatched Natural Killer Cells In Elderly High Risk Acute Myeloid Leukemia Patients: Biological and Clinical Results of A Pilot Study
- Author
-
Valeria Giudice, Maria Rosa Motta, Elena Urbani, Simonetta Rizzi, Roberto M. Lemoli, Michele Baccarani, Andrea Velardi, Alessandro Isidori, Andrea Bontadini, Beatrice Casadei, Giovanni Martinelli, Giuseppe Bandini, Loredana Ruggeri, Alessandra D'Addio, Stefania Paolini, Sara Trabanelli, Antonio Curti, Elisa Dan, and F. Fruet
- Subjects
Chemotherapy ,biology ,Cyclophosphamide ,business.industry ,medicine.medical_treatment ,CD3 ,Immunology ,Myeloid leukemia ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Fludarabine ,Graft-versus-host disease ,medicine.anatomical_structure ,medicine ,biology.protein ,Neural cell adhesion molecule ,Bone marrow ,business ,medicine.drug - Abstract
Abstract 4287 Purpose: To evaluate safety, feasibility and anti-leukemia potential of haploidentical KIR-L mismatched natural killer (NK) cell infusion in elderly high risk acute myeloid leukemia (AML) patients. Patients and Methods: Thirteen patients (5 active disease, 2 molecular relapse and 6 complete remissions) with median age 62 years (range 53–73) received NK cell infusion after immunosuppressive chemotherapy (fludarabine/cyclophosphamide), followed by interleukin-2. Highly purified CD56+CD3- NK cells from haploidentical KIR-L mismatched donors were used. The median number of infused NK cells was 2.74 × 106/Kg. T cells were less than 105/Kg. NK cell chimerism, phenotyping, and functional assays were performed. Results: No significant toxicity, including graft versus host disease, related to NK cell infusion was observed. Among patients with active disease, 1/5 obtained transient complete remission (CR), whereas 4/5 patients had no clinical benefit. Both patients in molecular relapse obtained CR, which lasted 9 and 4 months. Three/6 patients in morphologic CR are disease-free after 34, 32 and 18 months. Donor NK cells were demonstrated in the peripheral blood (PB) of all evaluable patients with a peak at day 10 after infusion and, in some cases, also in the bone marrow (BM). NK alloreactivity was demonstrated in vivo by the detection of donor-derived postinfusion NK clones capable of killing recipient targets. Conclusion: Infusion of purified CD56+CD3- NK cells is feasible and safe in elderly high risk AML patients. Adoptively transferred NK cells, which can be detected in PB and BM after infusion, are alloreactive against recipient cells and may induce an anti-leukemic activity. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2010
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.