scholarly journals Efficacy of Chemotherapeutic Regimens for Mantle Cell Lymphoma: A Systematic Review of Phase III Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Ali Jaan ◽  
Muhammad Tayyeb ◽  
Farhan Khalid ◽  
Muhammad Khawar Sana ◽  
Zahoor Ahmed ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Cell Transplant ◽  
Mantle Cell ◽  
Combination Regimens

Background: The mainstay treatment for mantle cell lymphoma (MCL) is chemotherapy ± immunotherapy. The standard chemotherapeutic regimens have limited efficacy in MCL when used alone. In this systematic review, we have assessed the efficacy and safety of various combination regimens for the treatment of MCL evaluated in phase III clinical trials. Methods: We performed a comprehensive systematic literature search on PubMed, Embase, clinicaltrials.gov, and Web of Science databases with the date of inception to May 2020. We used MeSH (Medical Subject Headings) terms for "mantle cell lymphoma", "treatment outcome" along with their keywords, and combined their results. Our search generated a total of 3572 articles. After excluding case reports, case series, observational studies, review articles, meta-analysis, phase I/II clinical trials, and pre-clinical studies, we included five phase III randomized clinical trials (RCTs) reporting the efficacy of combination regimens for MCL treatment. Results Data from five phase III RCTs was pooled with total N=1683 (newly diagnosed (ND), n=1242, relapsed/refractory (RR), n=441). 1610 patients were evaluable. Kluin-Nelemans et al. 2020 (n=560) studied induction with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) vs R-FC (rituximab, fludarabine, and cyclophosphamide) for ND-MCL with follow-up on maintenance with rituximab (R) -vs interferon alfa. At a median follow up of 7.6 years (y), median overall survival (mOS) was 6.4 vs 3.9 y (p=0.0054) in R-CHOP vs R-FC group, respectively. The median progression-free survival (mPFS) and mOS in the R-CHOP cohort on R maintenance were significantly better when compared to those on interferon alfa maintenance (mPFS, 5.4 y vs 1.9 y, p<0.001) (mOS, 9.8 y vs 7.1 y, p=0.0026). Robak et al. (2015) (n=487) assessed bortezomib in ND-MCL by substituting it for vincristine in the standard R-CHOP therapy. A cohort of MCL ineligible for stem cell transplant (SCT) was randomly assigned to either R-CHOP or VR-CAP (bortezomib replacing vincristine). At a median follow-up of 40 months (mo), mPFS was 24.7 mo vs 14.4 mo in VR-CAP vs R-CHOP (HR 0.63, p<0.001), respectively. Similar, relative improvements were reported in complete response (CR) (53% vs 42%, p=0.007) and 4-year OS was (64% [95% CI 56-71] vs 54% [95% CI 45-62]). Jin et al. (2018) (n=121) assessed R-CHOP vs VR-CAP in ND-MCL patients ineligible for SCT. After a median follow-up of 42.4 mo, mPFS for VR-CAP was better than R-CHOP (28.6 mo vs 13.9 mo, HR=0.7, p=0.157). The overall response rate (ORR) was almost similar in VR-CAP (97%) and R-CHOP (98%). The 4-year OS was 62% vs 61% in VR-CAP vs R-CHOP, respectively. Flinn et al. (2014) (n=74) studied the efficacy of bendamustine in combination with rituximab (BR) vs R-CHOP or R-CVP (R-CHOP minus doxorubicin) as induction regimens in ND-MCL. 36 patients received BR and 38 patients received R-CHOP/R-CVP. ORR was 94% vs 85% with BR vs R-CHOP/R-CVP, respectively. Hess et al. (2009) (n=162) evaluated temsirolimus in RR-MCL. The study population was randomized to either 175/75mg temsirolimus (arm A), 175/25mg temsirolimus (arm B), and the investigator's choice of chemotherapy (arm C). The mPFS was significantly better in arm A compared to arm C (4.8 mo vs 1.9 mo, HR 0.44 [97.5% CI 0.25-0.7], p=0.0009). Arm B had slight improvement but insignificant. Similarly, mOS was 12.8 mo in arm A (HR 0.8 [95% CI 0.5-1.28], p=0.35), and 8.8 in arm B (HR 0.96 [95% CI 0.60-1.54], p=0.87), when compared to 9.5 mo in arm C. Drelying et al. (2016) (n=280), studied temsirolimus in comparison with ibrutinib, RR-MCL with mPFS of 14.6 mo (95% CI 10.4-not estimable) vs 6.2 mo (95% CI 4.2-7.9), respectively. Toxicities were typically manageable. VR-CAP was associated with a higher incidence of toxicity (100%) vs R-CHOP (94%) majority of which was hematological. Thrombocytopenia was particularly more prominent with temsirolimus. Granulocytopenia was persistent in 30-40% in the R-FC cohort after 5 y. Conclusion: The chemo-immunotherapy combination is favorable compared to chemotherapy alone for the treatment of MCL. R-CHOP induction followed by rituximab maintenance in MCL shows favorable long-term safety and efficacy profile. Bortezomib substituting for vincristine in R-CHOP improves the efficacy outcomes. Ibrutinib-based regimens are superior to temsirolimus-based regimens. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

Prolongation of Progression Free Survival In Mantle Cell Lymphoma After RHCVAD: ASCT Consolidation or Rituximab Maintenance

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3570-3570
Author(s):  
Jennifer McQuade ◽  
Tahamtan Ahmadi ◽  
David Porter ◽  
Noelle Frey ◽  
Alison Wakoff Loren ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Primary Study ◽  
Cell Transplant ◽  
Data Set ◽  
Bulky Disease ◽  
Rituximab Maintenance ◽  
Mantle Cell

Abstract Abstract 3570 Mantle cell lymphoma (MCL) is a small B cell lymphoma, incurable with standard chemo-immunotherapy. The best initial treatment regimen remains unclear. Although it is generally acknowledged that aggressive approaches using combination chemotherapy and/or high dose chemotherapy can prolong survival, consensus on upfront treatment strategies for advanced MCL is currently lacking without randomized controlled data to guide treatment decisions. We conducted a retrospective cohort analysis to describe and compare the survival experiences of MCL patients at the University of Pennsylvania treated in the first-line setting with R-HCVAD (N=43) with or without autologous stem cell transplant (ASCT) or Rituximab maintenance. The primary study endpoints were PFS and OS as assessed by chart review and confirmed by SSDI database. Median follow up for all pts was 3 years. The median age was 53.7, and 76.7 % (n=33) were stage IV at diagnosis. 15 patients underwent consolidative ASCT. 11 pts received Rituximab maintenance. Comparing patients treated with R-HCVAD vs R-HCVAD + R maintenance vs. R-HCVAD + ASCT, there were no statistical differences in terms of age, ECOG PS, LDH, WBC, beta-2microglobulin, BM or GI involvement, bulky disease or blastoid variant at baseline. Median PFS for all patients was 3.9 years: R-HCVAD alone 2.1 years vs. R-HCVAD+R 3.9 years (P=0.02, HR 3.51, 95%CI: 1.2–10.2) vs R-HCVAD + SCT not reached (p=0.017, HR 3.7, 95%CI: 1.26–10.63). PFS survival rates at 2 years were 50%, 88% and 70%; 33%, 71/% and 63% respectively at 3 years, and 0%, 33% and 33 % at 5 years. 3 year OS for all patients was 84% (95% CI: 65–94) with no significant differences among the three approaches. Notably, only 1/8 patients treated with R-HCVAD + SCT relapsed after 2 years, with a median follow up of 4.8 years for these patients. Our data suggest a further improved PFS when R-HCVAD is consolidated with either Rituximab maintenance or ASCT. While neither of the two consolidative approaches appears superior in our limited data set, both show significant PFS prolongation when compared to R-HCVAD alone. Further prospective investigation of consolidative approaches after RHCVAD in a randomized fashion is warranted. Figure 1: Figure 1:. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Systematic Review of Relapsed or Refractory Mantle Cell Lymphoma (MCL) Clinical Trials: Implications for Decision Modeling

2014 ◽  
Vol 17 (7) ◽  
pp. A615-A616
Author(s):  
S. Sorensen ◽  
E. Dorman ◽  
Y. Xu ◽  
R. Sallum ◽  
F. Pan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Decision Modeling ◽  
Mantle Cell

In Vivo Purging with Hyper-CVAD Plus Rituximab Followed by Autologous Stem Cells Transplant and Rituximab Maintenance in Newly Diagnosed Mantle Cell Lymphoma: A Pilot Study for GISL (Italian Cooperative Study Group for Lymphoma).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5494-5494
Author(s):  
Edoardo Benedetti ◽  
Francesco Caracciolo ◽  
Sara Galimberti ◽  
Federico Papineschi ◽  
Matteo Pelosini ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Dose Intensity ◽  
High Dose ◽  
Cell Transplant ◽  
Rituximab Maintenance ◽  
Mantle Cell ◽  
High Dose Intensity

Abstract Previously untreated mantle cell lymphoma (MCL) are consistently associated with poor prognosis when treated with CHOP-like regimens. Typically the CR rate is 20–30%, median FFS = 10–16 months and median OS = 3 years. In the attempt to improve outcome we used a high dose intensity regimen such as Hyper-CVAD (HCVAD) with autologous stem cell transplant (ASCT). Twenty patients entered the study but only 10 up to now are valuable. Patients were apheresed after 2nd course of HCVAD and if apheresis (LPH) were PCR positive (Bcl1+/JH+) a second set of LPH were performed after completion of 4th cycle. To perform an in vivo purging Rituximab 375 mg/m2 was added at day +1 and +9 after last dose of ARA-C; GCSF 10μg/kg was commenced on day +5 until LPH was ultimated. Rituximab maintenance (375 mg/m2 once weekly for 4 consecutive weeks) started 2 month post-ASCT and was repeated every 6 months. Ten patients have completed 4 HCVAD and 7 /10 underwent ASCT and were conditioned with BEAM. After 4 HCVAD 7/10 patients were in CR and 3/7 in PR. After ASCT 1 PR obtained a CR, 1 PD obtained a VGPR and 5 CR maintained CR. Only 4CR post ASCT have received Rituximab maintenance and maintain CR. Two patients (1 CR blastic variant and 1 PR) refused ASCT and after 4 HCVAD received Rituximab maintenance and both are in CCR. Overall with a median follow up of 28.6 months (range 12–51) median survival is not reached. At 4 years 77.8% of patients are alive and PFS is 87.9%. Patients were monitored for bone marrow-MRD by PCR. Eight out of 10 were PCR+ at diagnosis and 7/8 were PCR negative after 4 HCVAD. After ASCT one PCR+ converted to PCR- and 1 PCR+ patient after 4 HCVAD converted to PCR- with Rituximab maintenance (refused ASCT). Conclusions: high dose intensity regimen HCVAD + Rituximab as in vivo purging and for maintenance allowed to collect tumor free grafts in 70% of PCR+patients at diagnosis and to reach an ORR of 100%, 7/10 CR and PR 3/10 (included 1 blastic variant). PCR negativity was obtained in 7/8 patients. One patient from PR converted to CR after ASCT and one after Rituximab maintenance (without ASCT); thus we might speculate that both high doses (BEAM) and Rituximab do play a role to increase the probability to obtain a CR and PCR-. Survival and PFS of 77.8% and 87.9% respectively at 4 years are encouraging. Further follow up and a higher enrolment of patients are needed to better define the role of HCVAD + Rituximab and ASCT to increase CR,PCR- PFS and OS in MCL.

Combined Immunochemotherapy with Rituximab Improves Overall Survival in Patients with Follicular and Mantle Cell Lymphoma: Updated Meta-Analysis Results.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2760-2760 ◽  
Author(s):  
Holger Schulz ◽  
Julia Bohlius ◽  
Nicole Skoetz ◽  
Sven Trelle ◽  
Marcel Reiser ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Disease Control ◽  
Mantle Cell Lymphoma ◽  
Full Text ◽  
Cell Lymphoma ◽  
Phase Iii ◽  
Cochrane Library ◽  
Indolent Lymphoma ◽  
Mantle Cell

Abstract Background Rituximab (R) has shown impressive response and prolonged progression free survival (PFS) in patients with indolent lymphoma when combined with CHOP. Randomized phase III trials adding rituximab to a variety of different regimen confirmed this benefit in both previously treated and untreated patients with advanced indolent lymphoma. Furthermore these trials indicating a trend towards improved overall survival (OS) for a combined immunochemotherapy with R. Here we report updated results of a comprehensive systematic review in this group of patients comparing R and chemotherapy with chemotherapy alone with respect to OS, disease control, overall response (OR) and toxicity. Methods Only randomized controlled trials (RCT) comparing R-chemo with chemotherapy alone in patients with newly diagnosed or relapsed indolent lymphoma and mantle cell lymphoma (MCL) were included. Medical databases (Cochrane Library, MEDLINE, EMBASE) and conference proceedings were searched (1990–2005). We included full-text and abstract publications. Number needed to treat (NNT) were calculated to facilitate interpretation. Results We included seven eligible RCTs involving a total of 1943 patients with follicular lymphoma (FL), MCL and other indolent lymphoma. Studies were published as full text (5), and in abstract form (2). OS was statistically significant improved in the R-chemo group when compared to chemotherapy alone (HR; hazard ratio: 0,65; 95% CI 0,54 – 0,78). OR (RR; relative risk: 1.21; 95% CI 1.16–1.27) and disease control (HR: 0.62; 95% CI 0.55–0.71) were also significantly superior after R-chemo. The RR for developing fever and leukocytopenia was significantly higher with R-chemo, but not associated with an increased risk of infection. Conclusion The systematic review demonstrated improved OS, OR and disease control for patients with indolent lymphoma and in the subgroups of follicular and mantle cell lymphoma when treated with R-chemo compared to chemotherapy alone.

scholarly journals A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma

2020 ◽  
Author(s):  
Martin Dreyling ◽  
Constantine S Tam ◽  
Michael Wang ◽  
Stephen D Smith ◽  
Marco Ladetto ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Mantle Cell Lymphoma ◽  
Kinase Inhibitor ◽  
Cell Lymphoma ◽  
Phase Iii ◽  
Cell Transplant ◽  
Clinical Trial Registration ◽  
Mantle Cell ◽  
Bruton Tyrosine Kinase ◽  
Phase Iii Study

Mantle cell lymphoma is an aggressive B-cell malignancy. Current frontline chemoimmunotherapies produce high response rates but relapse is inevitable. Furthermore, the elderly and those with comorbidities are precluded from standard regimens and stem cell transplant, leaving them with limited options. Targeted therapies, including Bruton tyrosine kinase inhibitors, are an effective treatment strategy in mantle cell lymphoma. Zanubrutinib is a potent next-generation Bruton tyrosine kinase inhibitor that has demonstrated complete and sustained Bruton tyrosine kinase occupancy, minimal off-target effects and favorable pharmacokinetic/pharmacodynamic properties. Described herein is an ongoing Phase III study comparing the efficacy and safety of zanubrutinib plus rituximab followed by zanubrutinib monotherapy versus bendamustine plus rituximab followed by observation in transplant-ineligible patients with previously untreated mantle cell lymphoma. Clinical Trial Registration: NCT04002297 ( ClinicalTrials.gov )

scholarly journals Long Term Follow-up in Mantle Cell Lymphoma Patients Treated with R-GemOx Followed By Consolidation and Rituximab Maintenance

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5337-5337
Author(s):  
Marta Garcia Recio ◽  
Leyre Bento ◽  
Sandra Pérez-León ◽  
Sara Aida Jiménez-Julià ◽  
Jordi Gines ◽  
...  
Keyword(s):  
High Risk ◽  
Mantle Cell Lymphoma ◽  
Therapeutic Approach ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
Age At Diagnosis ◽  
Cell Transplant ◽  
Rituximab Maintenance ◽  
Mantle Cell

Abstract Introduction: Six percent of all non-Hodgkin lymphomas (NHL) cases are mantle cell lymphoma (MCL). MCL has a poor prognosis and is considered incurable with current strategies. Intensive approaches are not applicable to most these patients considering the median age at diagnosis (70 years old). Due to the molecular events that drive MCL to be a lymphoma with an aggressive and indolent behavior as well as a tendency to clonal evolution (dysfunction of cell cycle, response to cellular damage and apoptosis), we present a global therapeutic approach which includes an effective induction with a low toxic profile, as well as consolidation and maintenance with the final aim of increasing and maintaining responses. Methods: From December-2008 to January-2018 all MCL patients treated in first line in our center were included. The therapeutic approach was based on an induction with R-GemOx (rituximab, gemcitabine and oxaliplatin) followed by consolidation with autologous stem cell transplant or ibritumomab tiuxetan followed by rituximab maintenance (Rm) (every 2 months for 2-3 years). Since 2016, all patients with less than complete response after induction/consolidation, received Ibrutinib 560 mg daily added to Rm. Standard prognostic variables were collected at diagnosis including MIPI; the response evaluation and follow-up was made considering Cheson criteria; for toxicity assessment, we used OMS grading scales of toxicity criteria. Overall survival (OS) and progression free survival (PFS) were estimated from the beginning of the treatment with the Kaplan-Meier method. Results: Thirteen treatment-naïve MCL patients were included from December-2008 to January-2018. Main characteristics of patients are shown in Table 1. Briefly, this is an old high risk series with a median age at diagnosis of 71 years old and poor prognosis (31% and 69% belong to intermediate and high risk MIPI groups, respectively). Two cases were refractory to R-GemOx induction (a blastic MCL and another case with high MIPI (7.7)). Four cases relapsed between 30 and 66 months after treatment was started. All cases with CR or PR after induction (n=11; 85%), obtained a CR at the end of the maintenance. One of the refractory cases after a second line followed by rituximab and ibrutinib maintenance also reached CR. Only 2 patients died (15%): one disease progression and another non-related pulmonary thromboembolism. The median follow-up was 51 months. Four-years OS was of 83% with a median PFS of 58 months (Figure 1). R-GemOx toxicity profile was manageable: most of them grade 1-2 neutropenia (43%), vomits (100%), diarrhea (30%) and anemia (30%). Grade 3-4 toxicity was scarce (neutropenia 14% and thrombocytopenia 36%). Conclusions: R-GemOx followed by consolidation and Rm should was an effective approach with manageable toxicity and excellent survival considering the median age and the high MIPI risk of the series. We plan to test this global approach in a prospective clinical trial. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document