Comparative Efficacy of First-Line Regimens in Relapsed/Refractory Mantle Cell Lymphoma (MCL): A Proportional Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-33
Author(s):  
Philip A Haddad ◽  
Dalia Hammoud ◽  
Kevin M. Gallagher
Keyword(s):  
Mantle Cell Lymphoma ◽  
English Language ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Meta Analysis ◽  
The Elderly ◽  
First Line ◽  
Mantle Cell ◽  
Duration Of Response ◽  
Btk Inhibitors

Introduction: Mantle cell lymphoma (MCL) is an incurable B-cell malignancy that disproportionately affects the elderly. After first-line therapy failure, relapsed/refractory MCL assumes a more aggressive and universally fatal course. Currently, several classes of chemo/biologic therapies are approved in the second line. However, these agents and their combinations have not been compared head-to-head. We conducted this proportional meta-analysis to evaluate their relative impact on selected clinical outcomes. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of relapsed/refractory MCL; trials that explored the efficacy of first-line approved antineoplastic agents and their combinations that comprised: BTK-inhibitors (Ibrutininb (IB), Acalabrutinib, Zanubrutinib), Bortezomib (Velcade, VEL), Venetoclax (VEN), Lenalidomide (LEN), and Bendamustine+Rituximab (B-R); and studies reporting types of responses and duration of response. Proportional meta-analysis was conducted using random-effects model. The respective 95% confidence intervals were calculated, and funnel plots were constructed. Results: Thirteen studies comprising a total of 1,264 participants were included. The pooled overall response rates, ORR (95%CI), of the regimens were: 74% (66,81) BTK-inhibitors, 39% (25,53) VEL, 34% (24,46) LEN, 85% (78,92) B-R, 75% (58,92) VEN-IB, and 88% (79,97) IB-R. The pooled complete responses, CR (95%CI), of the regimens were: 33% (20,47) BTK-inhibitors, 9% (5,13) VEL, 6% (4,9) LEN, 45% (36,54) B-R, 42% (22,63) VEN-IB, and 44% (30,58) IB-R. There were no significant differences in ORR and CR between BTK-inhibitors, B-R, VEN-IB, and IB-R. ORR of VEL and LEN also did not significantly differ. However, ORR and CR of the former group were significantly higher than those of the latter. The pooled partial responses, PR (95%CI), of the regimens were: 41% (32,50) BTK-inhibitors, 28% (20,38) VEL, 28% (15,43) LEN, 41% (35,47) B-R, 34% (15,53) VEN-IB, and 44% (30,58) IB-R. There were no significant differences between PR of the regimens. The weighted duration of responses in months, DOR (95%CI), of the regimens were: 20 BTK-inhibitors, 9 VEL, 16 LEN, and 20 B-R. Conclusions: This proportional meta-analysis is the first to compare the current regimens in first-line relapsed/refractory MCL. It indicates that BTK-inhibitors monotherapy, IB combinations with R or VEN, and B-R provide equivalent ORR and CR rates that are significantly better than VEL and LEN with notably longer duration of response. It also raises questions about whether there is an additional ORR and CR benefits when adding VEN or R to IB in this clinical setting. Disclosures No relevant conflicts of interest to declare.

Comparative Efficacy of First-Line Chemotherapy-Free Combinations in Chronic Lymphocytic Leukemia (CLL): A Network Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Philip A Haddad ◽  
Nowell Ganey ◽  
Kevin M. Gallagher
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
English Language ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Meta Analysis ◽  
The Elderly ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Significant Difference ◽  
Anti Cd20

Introduction: Chronic Lymphocytic Leukemia (CLL) is an incurable B-cell malignancy which disproportionately affects the elderly. Although first-line chemoimmunotherapy (CIT) improved CLL clinical outcomes, recent randomized trials revealed superior outcomes with novel chemotherapy-free combinations (CFC) incorporating anti-CD20 monoclonal antibodies and inhibitors of BTK or Bcl-2. So far, these CFC have not been compared head-to-head. We conducted this network meta-analysis to evaluate their relative efficacy to each other. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of CLL; trials that explored the efficacy of first-line CFC with Obinutuzumab (O), Rituximab (R), Ibrutinib (IB), Acalabrutinib (ACAL), Venetoclax (VEN) compared to standard CIT that included Chlorambucil (CHLOR) with either R or O, Bendamustine+Rituximab, or Fludarabine+ Cyclophosphamide+R; and phase 3 randomized studies reporting responses, progression, death, and adverse (AE) events. A frequentists network meta-analysis was conducted using netmeta package and random-effects model. Results: Five studies comprising a total of 2,272 participants were included. When O-based CFC data was analyzed, only ACAL-O had a significant lower relative risk (RR) of progression and death (P&D). There were no significant differences with respect to overall response rates (ORR), complete remission (CR), minimal residual disease (MRD), or grade >3 adverse events (Grd3+) among O-based CFC. When R-based CFC data was analyzed, IB and IB-R were not different with respect to RR of P&D, ORR, CR, MRD, or Grd3+. When the data was analyzed as CFC versus combined CIT, only ACAL-O was found to be significantly superior to other O- and R-based CFC with respect to RR of P&D. ORR and Grad3+ rates of O- and R-based CFC were not significantly different. While ACAL-O, IB-O, and VEN-O had superior CR and MRD rates compared to other CFC, there were no significant differences among each other. Conclusions: This network meta-analysis is the first to compare and rank first-line CFC therapies in CLL. It indicates that ACAL-O has a superior profile having the lowest RR of P&D without significant difference in Grd3+ among CFC. Disclosures No relevant conflicts of interest to declare.

Use of Cytarabine for Mantle Cell Lymphoma Treatment: 10 Years of Experience of a French Haematology Department

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1755-1755
Author(s):  
Marie-Pierre Gourin ◽  
Julie Abraham ◽  
Franck Trimoreau ◽  
Barbara Petit ◽  
Stephane Girault ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Intensive Therapy ◽  
Induction Treatment ◽  
Line Treatment ◽  
First Line ◽  
Mantle Cell ◽  
Cytological Aspect ◽  
First Line Treatment

Abstract Abstract 1755 Background: Mantle cell lymphoma (MCL) has been identified since 1994 in the Revised-European-American classification of Lymphoid neoplasm's. It's a rare and aggressive subtype representing 5% of all non-Hodgkin lymphomas (NHL) with a poor prognosis and a median overall survival (OS) of 30 to 43 months (m) due to refractory disease or frequently relapse. Chemotherapies including anthracyclines as CHOP regimen with or without rituximab are often used in first line treatment. Promising results have been obtained since 1998 with regimens including cytarabine and followed by intensive therapy with autologous stem-cell transplantation (ASCT) for younger patients. Since 1999 we adopted a policy of treating MCL with regimens including this molecule: younger and grafting patients received DHAP and rituximab (R-DHAP) regimen followed by intensive therapy with ASCT. Patients fit and aged over 65 years received 6 cycles of R-DHAP. Unfit patients over 65 years received R-COP-cytarabine regimen and older unfit and frail patients received cytarabine by subcutaneous (SC) weekly injections. We report a retrospective observational study of 10 years experience in our department. Methods: From 09/1999 to 09/2009, we collect all cases of patients with a MCL diagnosis and treated by cytarabine regimen in our haematology department. All diagnosis was reviewed by pathologist and cytologist. We collected clinical, biological, histological, cytological, prognosis, therapeutic monitoring and survey data from the database of the regional structure of reference of lymphoma in Limousin in France. A descriptive and survival analysis was performed using Statview software. Results: During this period, we followed 54 patients with MCL, median age 70,5 [45-87], sex ratio 2,6. Diagnosis was performed on associations of the following samples: biopsie in 72,2% (n=39), bone marrow cytological aspect and immunophenotyping in 48,1% (n=26), blood cytological aspect and immunophenotyping in 70,4% (n=38). Cyclin D1 overexpression in molecular analysis was detected in 79,6% (n=43). Ann Arbor stage I/II 7,4% (n=4), III/IV 92,6% (n=50). ECOG 0/1 83,3% (n=45), ECOG 2 16,7% (n=9). MIPI score was Lower Risk (LR) for 25,9% (n=14), Intermediate Risk (IR) for 27,8% (n=15) and Higher Risk (HR) for 46,3% (n=25). Median OS is significantly different among the MIPI score (p<0,0021) with 37,7 months for HR versus 72,6 months for IR and not reached for LR. First line treatment were distributed among SC weekly injections of cytarabine 13% (n=7), COP+/−R-cytarabine for 25,9% (n=14) and DHAP+/−R for 61,1% (n=33). ASCT was performed for 29,6% (n=16) followed induction treatment by DHAP+/−R. Median OS and PFS are respectively 59,4 and 46,3 months for the total population. Patients received SC cytarabine have a median OS of 37,7 months and median PFS 27,3 months. Patients received COP+/−R-cytarabine have a median OS of 29,4 months and PFS 17,7 months. And patients received DHAP+/−R have not reached median OS and PFS. For patients received ASCT, median OS and PFS are not reached versus respectively 46,3 and 33,5 months for ungrafted patients. Median follow-up is 35,4 months [1-124,7] for all patients, 37,7 months [1,1-59,3] for patients treated by SC cytarabine, 18,1 months [2,6-81,9] for patients treated by COP+/−R-cytarabine and 39,8 months [1-124,7] for patients treated by DHAP+/−R. Conclusion: The MIPI score was calculated a posteriori and validated in our series of patients distinguishing three different populations with significantly different survival (p<0,0021). Since 10 years, we usually used cytarabine in first-line treatment of MCL. Cytarabine regimen is associated with other molecule and adapted by age, comorbidities and renal function. In real life, the use of this molecule seems provide interesting results in term of survival and PFS particularly for younger receiving dose intensified regimens by R-DHAP followed by intensive therapy with ASCT. Several clinical trials include now cytarabine in their therapeutic schemes. Disclosures: No relevant conflicts of interest to declare.

Management of Mantle Cell Lymphoma in the Elderly: Current and Potential Strategies

Drugs & Aging ◽  
2013 ◽  
Vol 30 (12) ◽  
pp. 979-986 ◽  
Author(s):  
Marguerite Vignon ◽  
Marie-Dominique Venon ◽  
Olivier Hermine ◽  
Richard Delarue
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
The Elderly ◽  
Mantle Cell

Effectiveness and tolerability of first-line autologous stem cell transplant and maintenance rituximab for mantle cell lymphoma

2017 ◽  
Vol 53 (3) ◽  
pp. 347-351
Author(s):  
Umberto Falcone ◽  
Haiyan Jiang ◽  
Shaheena Bashir ◽  
Richard Tsang ◽  
Vishal Kukreti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
First Line ◽  
Mantle Cell

scholarly journals Radioimmunotherapy for Mantle Cell Lymphoma: 5-Year Follow-up of 90 Patients from the International RIT-Registry

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5263-5263
Author(s):  
Karin Hohloch ◽  
Christine Windemuth-Kieselbach ◽  
Pier Luigi Zinzani ◽  
Roberto E. Cacchione ◽  
Wojciech Jurczak ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Mantle Cell Lymphoma ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Primary Therapy ◽  
First Line ◽  
Advisory Committees ◽  
Mantle Cell

To assess the efficacy of radioimmunotherapy (RIT) with 90yttrium-ibrutinib-tiuxetan (90Y-IT) in mantle cell lymphoma, data from 90 patients registered in the RIT Network with a median follow-up (FU) of 5.5 years after RIT were evaluated. 90Y-IT was given as first-line therapy in 45 (50%) (consolidation 44 pts., primary therapy 1 pt.) and at relapse in 45 (50%) patients (consolidation 24 pts., recurrence 12 pts., therapy refractory 3 pts., conditioning 2 pts., other 4 pts.). As a first-line treatment, 30 patients (pts.) (67%) achieved CR, 10 pts. (22%) PR%., 1 pt. (2%) PD, and for 4 pts. (9%) no response data was available. At relapse, CR was achieved in 17 pts. (38%), PR in 6 pts. (13%), SD in 2 pts. (4%), and 6 pts. (13%) had PD, while the response was not documented for 14 pts. (31%). After a median FU of 5.5 years, median PFS for all patients was 2.11 (95%CI: 1.03-2.32) years, and median OS was 4.05 (95%CI 2.79-7.21) years. Eleven pts. (12.2%) developed second malignancy. In conclusion, this is the largest report of MCL pts. treated with 90Y-IT to date. 90Y-IT was most often used as consolidation after first- and second-line chemotherapy and may improve the results achieved using chemoimmunotherapy alone. However, the results are less encouraging compared to treatment with small molecules such as ibrutinib. Disclosures Zinzani: TG Therapeutics: Honoraria, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; 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; 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. Jurczak:Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Roche: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bayer: Research Funding; Gilead: Research Funding; MorphoSys: Research Funding; Incyte: Research Funding; Novo Nordisk: Research Funding; Servier: Research Funding; TG Therapeutics: Research Funding; Celtrion: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Truemper:Seattle Genetics, Inc.: Research Funding; Takeda: Consultancy, Research Funding; Roche: Research Funding; Nordic Nanovector: Consultancy; Mundipharma: Research Funding; Janssen Oncology: Consultancy. Scholz:Janssen-Cilag: Consultancy; Hexal: Consultancy; Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Pfizer: Speakers Bureau; Roche: Consultancy; GILEAD: Consultancy, Speakers Bureau; Daiichi Sankio: Consultancy. OffLabel Disclosure: Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin) is approved for treatment of patients with relapsed follicular lymphoma and as consolidation therapy after chemo(immuno)therapy of patients with follicular lymphoma.

BTK Inhibitors Differentially Induce Apoptosis but Similarly Suppress Chemotaxis and Lipid Accumulation in Mantle Cell Lymphoma

2020 ◽  
Author(s):  
Zhuojun Liu ◽  
Jia Liu ◽  
Tainming Zhang ◽  
Lin Li ◽  
Shuo Zhang ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Caspase 3 ◽  
Cell Lymphoma ◽  
Stimulated Raman Scattering ◽  
Biological Effects ◽  
Immunoblot Analysis ◽  
Mantle Cell ◽  
Apoptotic Genes ◽  
Btk Inhibitors ◽  
Cell Chemotaxis

Abstract Background: The more selective second-generation BTK inhibitors (BTKis) Acalabrutinib and Zanubrutinib and the first-generation BTK inhibitor (BTKi) Ibrutinib are highlighted by their clinical effectiveness in mantle cell lymphoma (MCL), however, similarities and differences of their biological and molecular effects on anti-survival of MCL cells induced by these BTKis with distinct binding selectivity against BTK remain largely unknown. Methods: AlamarBlue assays were performed to define cytotoxicity of BTKis against MCL cells, Jeko-1 and Mino. Cleaved PARP and caspase-3 levels were examined by immunoblot analysis to study BTKi-induced apoptotic effects. Biological effects of BTKis on MCL-cell chemotaxis and lipid droplet (LD) accumulation were examined in Jeko-1, Mino and primary MCL cells via Transwell and Stimulated Raman scattering imaging analysis respectively. Enzyme-linked immunoassays were used to determine CCL3 and CCL4 levels in MCL-cell culture supernatants. RNA-seq analyses identified BTKi targets which were validated by quantitative RT-PCR (qRT-PCR) and immunoblot analysis. Results: Acalabrutinib and Zanubrutinib induced moderate apoptosis in Ibrutinib high-sensitive JeKo-1 cells and Ibrutinib low-sensitive Mino cells, which was accompanied by cleaved PARP and caspase-3. Such effects might be caused by the stronger ability of Ibrutinib to upregulate the expression of pro-apoptotic genes, such as HRK, GADD45A , and ATM , in JeKo-1 cells than in Mino cells, and the expression of such apoptotic genes was slightly changed by Acalabrutinib and Zanubrutinib in both JeKo-1 and Mino cells. Further, Acalabrutinib, Zanubrutinib and Ibrutinib reduced MCL-cell chemotaxis with similar efficiency, due to their similar abilities to downmodulate chemokines, such as CCL3 and CCL4. Also, these three BTKis similarly suppressed MCL-cell LD accumulation via downregulating lipogenic factors, DGAT2, SCD, ENPP2 and ACACA without significant differences. Conclusion: BTKis demonstrated differential capacities to induce MCL-cell apoptosis due to their distinct capabilities to regulate the expression of apoptosis-related genes, and similar biological and molecular inhibitory effects on MCL-cell chemotaxis and LD accumulation.

scholarly journals Erratum on “Non-indolent mantle cell lymphoma at a single public hospital in Brazil: real world first-line treatment cohort study data”

2020 ◽  
Vol 42 (2) ◽  
pp. 194
Author(s):  
Sergio Augusto Buzian Brasil ◽  
Carolina Colaço ◽  
Tomas Barrese ◽  
Roberto P. Paes ◽  
Cristina Bortolheiro ◽  
...  
Keyword(s):  
Cohort Study ◽  
Mantle Cell Lymphoma ◽  
Real World ◽  
Public Hospital ◽  
Cell Lymphoma ◽  
Study Data ◽  
Line Treatment ◽  
First Line ◽  
Mantle Cell ◽  
First Line Treatment
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