scholarly journals Treatment of Older Patients With Mantle Cell Lymphoma (MCL): Long-Term Follow-Up of the Randomized European MCL Elderly Trial

2020 ◽  
Vol 38 (3) ◽  
pp. 248-256 ◽  
Author(s):  
Hanneke C. Kluin-Nelemans ◽  
Eva Hoster ◽  
Olivier Hermine ◽  
Jan Walewski ◽  
Christian H. Geisler ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Random Assignment ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Mantle Cell ◽  
Grade 3

PURPOSE In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209 ), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance. PATIENTS AND METHODS Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression. We compared progression-free survival from the second randomization and overall survival (OS) from the first or second randomizations. RESULTS After a median follow-up time of 7.6 years, the previously described difference in OS between the induction arms persisted (median, 6.4 years after R-CHOP [n = 280] v 3.9 years after R-FC [n = 280]; P = .0054). Patients responding to R-CHOP had median progression-free survival and OS times of 5.4 and 9.8 years, respectively, when randomly assigned to rituximab (n = 87), compared with 1.9 years ( P < .001) and 7.1 years ( P = .0026), respectively, when randomly assigned to interferon alfa (n = 97). In 58% and 32% of patients treated with R-CHOP, rituximab maintenance was still ongoing 2 and 5 years from start of maintenance, respectively. After R-FC, rituximab maintenance was associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). Toxicity of rituximab maintenance was low after R-CHOP (grade 3-4 leukopenia or infection < 5%) but more prominent in patients on rituximab maintenance after R-FC, in whom grade 3-4 leukopenia (up to 40%) and infections were frequent (up to 15%). CONCLUSION The excellent results of R-CHOP followed by rituximab maintenance until progression for older patients with MCL persisted in a mature follow-up. Prolongation of rituximab maintenance beyond 2 years is effective and safe.

High Remission Rates and Prolonged Progression Free Survival in Newly Diagnosed Patients with Mantle Cell Lymphoma Treated with R-MACLOIVAM-T

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3597-3597 ◽  
Author(s):  
Peter J Hosein ◽  
Daniel Morgensztern ◽  
Francine Coleman ◽  
Gail Walker ◽  
Maricer Escalon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mantle Cell Lymphoma ◽  
Relapse Rate ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Mantle Cell ◽  
Grade 3

Abstract Background: Mantle cell lymphoma (MCL) is an unfavorable subtype of B-cell non-Hodgkin lymphoma characterized by median progression-free survival (PFS) and median overall survival (OS) of only 1.5 and 3–4 years respectively. Although high-dose therapy and an autotransplant may prolong OS, it does not result in a long-term disease free survival. Therefore, there is a need for novel therapeutic approaches for this entity. Methods: We conducted a single-arm phase II study in subjects with newly-diagnosed MCL to assess efficacy and safety of a novel intensive regimen R-MACLO-IVAM-T, a modification of a protocol designed by Magrath et al (JCO1996;14:925). The study size of 22 patients was based on precision of a two-sided 95% confidence interval for the 18-month progression free survival rate. Eligible subjects had a confirmed diagnosis of MCL using WHO criteria, age 18–75 years, ECOG PS ≤ 2, adequate organ function and no history of HIV or prior cancer. Lymphoma extent at presentation was assessed by standard staging procedures as well as esophagogastroduodenoscopy and colonoscopy. Prior to initiating thalidomide maintenance, subjects were enrolled in the STEPS® program. Cycle 1 consisted of R-MACLO: rituximab 375 mg/m2 IV on day 1, doxorubicin 45 mg/m2 IV on day 1, cyclophosphamide 800 mg/m2 IV on day 1 and 200 mg/m2/day on days 2–5, vincristine 1.5 mg/m2 on days 1 and 8 capped to 2mg, methotrexate 1.2 g/m2 IV on day 10 over 1 hour followed by 5.52 g/m2 IV over 23 hours followed by leucovorin 36 hours later. G-CSF was begun on day 13. When the ANC was >1.5×109/L, cycle 2 with R-IVAM was begun: rituximab 375 mg/m2 IV day 1, cytarabine 2 g/m2 IV every 12 hours on days 1 and 2, etoposide, 60 mg/m2 on days 1–5 and ifosfamide 1.5 g/m2 on days 1–5 with mesna. Fourteen days after ANC recovery from cycle 2, cycles 3 and 4 were given in identical fashion to 1 and 2. Four weeks after ANC recovery from cycle 4, subjects were re-staged and responses were assessed by standard criteria. Subjects achieving CR at the end of therapy received thalidomide 200 mg/day until MCL relapse or intolerable toxicity. Results: Accrual started in 4/2004 and ended in 3/2008 when the planned 22 subjects were enrolled. All subjects were evaluable for toxicity and 21 were evaluable for response. Median age was 56.5 years (range 39–73). All subjects had at least stage 3 disease with bone marrow involvement in 19 and gastrointestinal involvement in 10. Distribution according to IPI: 0–1 factor, 3; 2 factors, 8; 3 factors, 8; and 4 factors, 3. Twenty subjects had diffuse variant and 2 had blastic variant. Nineteen subjects completed all 4 cycles of therapy; treatment was stopped in 2 subjects after 2 and 3 cycles respectively, and one subject died during the first cycle. Of the 21 subjects completing 2 cycles of therapy, 20 achieved CR and one PR. Two subjects relapsed at 9 and 33 months respectively, while 19 remain relapse free after median follow-up of 25 months (range 5–51). With a total follow-up of 545 months, the estimated relapse rate is 4.4 per 100 patients per year. There were two deaths: 1 from sepsis on cycle 1 day 8 and the other in CR at 38 months from non-small cell lung cancer diagnosed 19 months after MCL. Common severe toxicities were grade 3–4 neutropenia, thrombocytopenia and anemia in 33%, 19% and 17% of R-MACLO cycles and in 50%, 88% and 68% of R-IVAM cycles respectively. There were 14 bacteremias in 82 cycles, 12 of which were after R-IVAM therapy. Six episodes of reversible grade 1–2 renal toxicity occurred after methotrexate. The thalidomide maintenance dose was reduced in 6 subjects due to grade 3–4 neutropenia and reduced or stopped in 8 subjects because of grade 3–4 peripheral neuropathy. Patients remain under follow-up for relapse and survival. Conclusions: R-MACLO-IVAM-T results in a high overall response rate of 100% (95% CR and 5% PR) and a low relapse rate. At a median follow-up of 25 months, median PFS and OS were not reached. The 2-year actuarial PFS of 94% compares favorably with previously reported 2-year actuarial PFS of 40% and 67% for CHOP-like regimens without and with upfront bone marrow transplantation (Blood2005;105: 2677). The contribution of thalidomide maintenance to this outcome requires additional study. A multicenter clinical trial is suggested.

Early Consolidation with Myeloablative Radiochemotherapy Followed by Autologous Stem Cell Transplantation in First Remission Significantly Prolongs Progression-Free Survival in Mantle Cell Lymphoma - Long Term Follow up of a Prospective Randomized Trial of the European MCL Network.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 7-7 ◽  
Author(s):  
Martin H. Dreyling ◽  
Georg Lenz ◽  
Eva Schiegnitz ◽  
Achiel van Hoof ◽  
Christian Gisselbrecht ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
Free Survival ◽  
Mantle Cell ◽  
First Remission

Abstract Mantle cell lymphoma (MCL) is a distinct subtype of malignant lymphoma with an especially poor prognosis and a median survival of only 3–4 years. In 1996, the European MCL Network initiated a randomized trial to improve the otherwise dismal outcome of MCL, comparing early consolidation with myeloablative radiochemotherapy (TBI 12 gray, cyclophosphamide 120 mg/kg bw) followed by autologous stem cell transplantation (ASCT) to a conventional a -interferon maintenance (6x106 IE IFNa 3x weekly) in first remission after a CHOP-like induction regimen. Until March 2004, a total of 269 previously untreated patients (up to 65 years) were randomized upfront. 189 (82%) of 230 patients with advanced stage MCL completed initial induction chemotherapy and 142 (75%) achieved either a complete (45 pts., 24%) or partial response (97 pts, 51%). 122 pts proceeded to consolidation therapy, 62 pts received ASCT consolidation and 60 patients were assigned to IFN maintenance. Patients in the ASCT study arm experienced a significantly longer progression-free survival (PFS) as compared to patients in the IFNa arm. The PFS at 2 years was 73% after ASCT as compared to only 43% in the IFNa arm (p = 0.0108). Similar results were achieved in the intent to treat analysis of all initially randomised MCL patients (p=0.0001). Accordingly, this advantage resulted in a trend towards an improved overall survival (OS) in the ASCT arm. After a follow-up of up to nearly 7 years (median follow-up of patients: 2.8 years), 3 year survival after ASCT was 83% in comparison to 77% under IFNa maintenance (p = 0.18). As expected, acute toxicity was higher in the ASCT group with an early mortality of 4.8%, whereas long-term effects were more frequently encountered under IFNa maintenance. Conclusion : In first line treatment of advanced stage MCL, dose-intensified consolidation with myeloablative radiochemotherapy followed by ASCT after CHOP-like induction results in a significant prolongation of PFS. Current study concepts evaluate the benefits of combined immuno-chemotherapy to further improve the overall survival.

scholarly journals Rituximab and Bendamustine (BR) Compared with Rituximab, Bendamustine, and Cytarabine (R-BAC) in Previously Untreated Elderly Patients with Mantle Cell Lymphoma

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6089
Author(s):  
Giulia Bega ◽  
Jacopo Olivieri ◽  
Marcello Riva ◽  
Greta Scapinello ◽  
Rossella Paolini ◽  
...  
Keyword(s):  
Propensity Score ◽  
Elderly Patients ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Mantle Cell ◽  
Grade 3

Background: Rituximab plus bendamustine (BR), and rituximab, bendamustine, and cytarabine (R-BAC) are well-known induction therapies in elderly patients with mantle cell lymphoma (MCL), according to clinical guidelines. However, a direct comparison between the two regimens has never been performed. Methods: In this multicentre retrospective study, we compared the outcome of patients with newly diagnosed MCL, treated with BR or R-BAC. Primary endpoint was 2-year progression-free survival (PFS). Inclusion bias was assessed using a propensity score stratified by gender, age, MCL morphology, and MIPI score. Results: After adjusting by propensity score, we identified 156 patients (53 BR, 103 R-BAC) with median age of 72 (53–90). Median follow-up was 46 months (range 12–133). R-BAC was administered in a 2-day schedule or with attenuated dose in 51% of patients. Patients treated with R-BAC achieved CR in 91% of cases, as compared with 60% for BR (p < 0.0001). The 2-year PFS was 87 ± 3% and 64 ± 7% for R-BAC and BR, respectively (p = 0.001). In terms of toxicity, R-BAC was associated with significantly more pronounced grade 3–4 thrombocytopenia than BR (50% vs. 17%). Conclusions: This study indicates that R-BAC, even when administered with judiciously attenuated doses, is associated with significantly prolonged 2-year PFS than BR in elderly patients with previously untreated MCL.

Long-term follow-up of previously untreated patients (pts) with chronic lymphocytic leukemia (CLL) treated with ofatumumab (OFA) and chlorambucil (CHL): Final analysis of the phase 3 COMPLEMENT 1 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7528-7528
Author(s):  
Fritz Offner ◽  
Tadeusz Robak ◽  
Ann Janssens ◽  
Govind Babu Kanakasetty ◽  
Janusz Kloczko ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Final Analysis ◽  
Lymphocytic Leukemia ◽  
Primary Analysis ◽  
Free Survival ◽  
Anti Cancer ◽  
Long Term Follow Up ◽  
Grade 3

7528 Background: Previously in the COMPLEMENT 1 study, treatment with OFA and CHL in pts with untreated CLL had shown a significant improvement in the progression-free survival (PFS) compared with CHL alone, and was well tolerated. Here, we report the final overall survival (OS) analysis of the 5-year (y) follow-up, updated investigator-assessed PFS and safety from the study. Methods: Untreated pts, not fit for fludarabine-based therapy (due to advanced age or co-morbidities) were randomized 1:1 to OFA+CHL or CHL alone. Pts in OFA+CHL arm received OFA (Cycle 1: 300 mg day (d) 1, 1000 mg d8; subsequent cycles: 1000 mg d1) in addition to CHL (10 mg/m2, d1-7) for 3 to 12 cycles of 28 d each. Pts in CHL arm received CHL only. Results: Overall, 447 pts were randomized to OFA+CHL (n = 221) or CHL (n = 226); 168 (76%) and 164 (73%) pts completed the scheduled treatments, respectively. Baseline characteristics were similar in both arms. The investigator-assessed median PFS was 23.4 months (mos) in the OFA+CHL arm and 14.7 mos in the CHL arm (HR: 0.61 [95% CI 0.49, 0.76], p < 0.001). Median OS could not be estimated for the OFA+CHL arm and was 84.7 mos for the CHL arm (HR: 0.88 [95% CI 0.65, 1.17], p = 0.363). Estimated OS rate (95% CI) at 5 y was 68.5% (61.5%, 74.5%) in the OFA+CHL arm, and 65.7% (58.6%, 71.9%) in the CHL arm. Post-treatment anti-cancer therapy after discontinuation was received by a greater proportion of pts in the CHL (66%) vs. OFA+CHL (56%), and started earlier in the CHL arm (486 d) vs. OFA+CHL (743 d) arm. Overall, 84 (39%) pts in the OFA+CHL, and 99 (44%) pts in the CHL arms died during the study with 5 on-treatment deaths in each group. Grade ≥3 adverse events were seen in 64% and 48% of pts in the OFA+CHL vs. CHL arms, respectively, most common being (≥5% in either arm) neutropenia (26% vs. 15%), thrombocytopenia (5% vs. 10%), pneumonia (9% vs. 5%), and anemia (5% vs. 5%). Conclusions: This 5-y survival follow-up analysis supported the results from primary analysis with an estimated 12% (not significant) and 39% risk reduction in OS and PFS, respectively, in the OFA+CHL arm compared with the CHL arm. No new safety concerns were observed in the OFA+CHL arm. Clinical trial information: NCT00748189.

scholarly journals First-Line Treatment of Patients With Indolent Non-Hodgkin Lymphoma or Mantle-Cell Lymphoma With Bendamustine Plus Rituximab Versus R-CHOP or R-CVP: Results of the BRIGHT 5-Year Follow-Up Study

2019 ◽  
Vol 37 (12) ◽  
pp. 984-991 ◽  
Author(s):  
Ian W. Flinn ◽  
Richard van der Jagt ◽  
Brad Kahl ◽  
Peter Wood ◽  
Tim Hawkins ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Time To Event ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Mantle Cell ◽  
Duration Of Response ◽  
Long Term Follow Up

PURPOSE The BRIGHT study ( ClinicalTrials.gov identifier: NCT00877006) was initiated to compare the efficacy and safety of bendamustine plus rituximab (BR) with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP) for treatment-naive patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma. This publication provides long-term follow-up data. PATIENTS AND METHODS Patients were monitored for a minimum of 5 years after completion of study treatment for the time-to-event end points of progression-free survival (PFS), event-free survival, duration of response, and overall survival per investigator assessment. Data on the number of patients who received second-line anticancer treatment and the occurrence of other malignancies were also collected. RESULTS The medians were not reached for any of the time-to event end points for either the BR or R-CHOP/R-CVP study treatment groups by study completion. PFS rates at 5 years were 65.5% in the BR treatment group and 55.8% in the R-CHOP/R-CVP group. The difference in PFS was considered significant with a hazard ratio of 0.61 (95% CI, 0.45 to 0.85; P = .0025). The hazard ratio for event-free survival and duration of response ( P = .0020 and .0134, respectively) also favored the BR regimen over R-CHOP/R-CVP. However, no significant difference in overall survival was observed. The overall safety profiles of BR, R-CHOP, and R-CVP were as expected; no new safety data were collected during long-term follow-up. A higher number of secondary malignancies was noted in the BR treatment group. CONCLUSION Overall, BR demonstrated better long-term disease control than R-CHOP/R-CVP and should be considered as a first-line treatment option for patients with indolent and mantle-cell lymphoma.

R-CHOP Versus R-FC Followed by Maintenance with Rituximab Versus Interferon-Alfa: Outcome of the First Randomized Trial for Elderly Patients with Mantle Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 439-439 ◽  
Author(s):  
J.C. Kluin-Nelemans ◽  
E. Hoster ◽  
J. Walewski ◽  
S. Stilgenbauer ◽  
C. H. Geisler ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Mantle Cell Lymphoma ◽  
Induction Therapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Interferon Alfa ◽  
Rituximab Maintenance ◽  
Remission Duration ◽  
Mantle Cell ◽  
Grade 3

Abstract Abstract 439 Introduction. The prognosis of elderly patients with mantle cell lymphoma (MCL) is poor. Despite R-CHOP, only low rates of complete remissions (CR) are obtained and almost all patients relapse. Median overall survival (OS) used to be far below 5 years. Within the European MCL Network we performed a randomized intergroup trial to investigate both whether a fludarabine-containing induction regimen could improve the CR-rate, and whether maintenance with rituximab could prolong remission duration. Methods. Patients with stage II-IV MCL >60 yrs not eligible for high-dose therapy were randomized between either 8 × R-CHOP-21 (day 1: rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, max 2 mg and day 1–5 prednisone 100 mg) or 6 × R-FC-28 (rituximab 375 mg/m2 day 1, fludarabine 30 mg/m2 + cyclophosphamide 250 mg/m2, both iv day 1–3). Responding (CR, CRu, PR) patients underwent a second randomization between maintenance with rituximab one dose every 2 months or interferon-alfa (IFN; regular IFN weekly 3×3 MIU or pegylated IFN 1×1 μg/kg), both given until progression. First randomisation for induction therapy - R-CHOP vs R-FC: Between Jan 2004 and Oct 2010, 560 patients were entered; 457 were evaluable for response to induction. Median age was 70 yrs, 70% male, 83% stage IV, 41% intermediate and 50% high-risk MIPI. Whereas CR rates after R-FC and R-CHOP were similar (38 vs 34% CR, 52 vs 50% CR/CRu, respectively), the overall response rate was lower after R-FC (78% vs 87%; p=0.0508). Progressive disease was more frequent during R-FC (15% vs 5%). Of note, median OS was significantly inferior after R-FC (40 vs 64 months; p=0.0072). More patients died after initial progression (14% vs 4%) or in first remission (11% vs 3%) in the R-FC arm compared to R-CHOP. Hematologic grade 3–4 toxicities were more frequent during R-FC, especially thrombocytopenia (40% vs 17%). Non-hematologic grade 3–4 toxicity was rare (below 7% each), except neutropenic fever (12% R-FC; 18% R-CHOP) and infections (16% R-FC; 14% R-CHOP). Second randomisation for maintenance therapy - Interferon-alpha vs Rituximab: From the responding patients, 310 underwent the second randomization. Sixty-one percent of patients had a CR/CRu upon induction therapy. Fifty-eight percent had received R-CHOP induction. Rituximab maintenance almost doubled the remission duration compared with IFN (at 4-yrs 57% vs 26% in remission; HR 0.54, 0.35–0.87; p=0.0109). Overall survival did not differ between both maintenance arms (p=0.17). However, the subcohort of R-CHOP-treated patients showed a significant advantage after rituximab maintenance (4-yr OS 87% vs 57% after IFN; p=0.0061). Hematologic grade 3–4 toxicity was higher in the IFN arm (leukocytopenia 33% vs 16%; thrombocytopenia 15% vs 6%); non-hematologic grade 3–4 toxicity was rare, except for infections (8% IFN; 7% rituximab). R-FC followed by rituximab resulted in the highest infection rate (CTC grades 1–4: 50%), whereas all other combinations (R-CHOP followed by rituximab or IFN, and R-FC followed by IFN) ranged between 25–35%. Patients in CR/CRu or PR after induction who did not receive any maintenance for various reasons, mainly based upon patient's decisions or ongoing cytopenia after induction (n = 104), had a poor outcome (median remission duration 18 months). Conclusions. Induction therapy with R-FC is discouraged for elderly patients with MCL, whereas R-CHOP induction followed by rituximab maintenance should be considered the new standard for elderly MCL patients, to which new regimens need to be compared. Disclosures: Off Label Use: rituximab maintenance for mantle cell lymphoma. Geisler:Roche: Consultancy, Research Funding; Celgene: Consultancy; GSK: Consultancy. Tilly:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hiddemann:Roche Pharma: Honoraria, Research Funding. Dreyling:Roche: Research Funding, Scientific advisory board, Speakers Bureau.

scholarly journals Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study

2019 ◽  
Vol 37 (31) ◽  
pp. 2815-2824 ◽  
Author(s):  
Emmanuel Bachy ◽  
John F. Seymour ◽  
Pierre Feugier ◽  
Fritz Offner ◽  
Armando López-Guillermo ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Long Term Results ◽  
Induction Treatment ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
To Receive

PURPOSE The PRIMA study (ClinicalTrials.gov identifier: NCT00140582 ) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety. METHODS Patients (> 18 years of age) with previously untreated high–tumor-burden follicular lymphoma were nonrandomly assigned to receive one of three immunochemotherapy induction regimens. Responding patients were randomly assigned (stratified by induction regimen, response to induction treatment, treatment center, and geographic region) 1:1 to receive 2 years of rituximab maintenance (375 mg/m2, once every 8 weeks), starting 8 weeks after the last induction treatment, or observation (no additional treatment). All patients in the extended follow-up provided their written informed consent (data cutoff: December 31, 2016). RESULTS In total, 1,018 patients completed induction treatment and were randomly assigned to rituximab maintenance (n = 505) or observation (n = 513). Consent for the extended follow-up was provided by 607 patients (59.6%) of 1,018 (rituximab maintenance, n = 309; observation, n = 298). After data cutoff, median PFS was 10.5 years in the rituximab maintenance arm compared with 4.1 years in the observation arm (hazard ratio, 0.61; 95% CI, 0.52 to 0.73; P < .001). No OS difference was seen in patients randomly assigned to rituximab maintenance or observation (hazard ratio, 1.04; 95% CI, 0.77 to 1.40; P = .7948); 10-year OS estimates were approximately 80% in both study arms. No new safety signals were observed. CONCLUSION Rituximab maintenance after induction immunochemotherapy provides a significant long-term PFS, but not OS, benefit over observation.

scholarly journals Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma

Blood ◽  
2009 ◽  
Vol 113 (18) ◽  
pp. 4144-4152 ◽  
Author(s):  
Constantine S. Tam ◽  
Roland Bassett ◽  
Celina Ledesma ◽  
Martin Korbling ◽  
Amin Alousi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Autologous Transplantation ◽  
Progression Free Survival ◽  
Long Term Outcome ◽  
Free Survival ◽  
Mantle Cell ◽  
First Remission

Abstract In this study, we analyzed the long-term outcome of a risk-adapted transplantation strategy for mantle cell lymphoma in 121 patients enrolled in sequential transplantation protocols. Notable developments over the 17-year study period were the addition of rituximab to chemotherapy and preparative regimens and the advent of nonmyeloablative allogeneic stem cell transplantation (NST). In the autologous transplantation group (n = 86), rituximab resulted in a marked improvement in progression-free survival for patients who received a transplant in their first remission (where a plateau emerged at 3-8 years) but did not change the outcomes for patients who received a transplant beyond their first remission. In the NST group, composed entirely of patients who received a transplant beyond their first remission, durable remissions also emerged in progression-free survival at 5 to 9 years. The major determinants of disease control after NST were the use of a peripheral blood stem cell graft and donor chimerism of at least 95%, whereas the major determinant of death was immunosuppression for chronic graft-versus-host disease. Our results show that long-term disease-free survival in mantle cell lymphoma is possible after rituximab-containing autologous transplantation for patients in first remission and after NST for patients with relapsed or refractory disease.

Immunochemotherapy (R-MCP) Is Not Superior to Chemotherapy (MCP) Alone in Advanced Mantle Cell Lymphoma - 42 Months Follow Up Results of the OSHO 39 Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4474-4474
Author(s):  
Michael Herold ◽  
Antje Haas ◽  
Stephanie Srock ◽  
Sabine Neser ◽  
Kathrin H. Al Ali ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Randomised Trial ◽  
Progression Free Survival ◽  
Striking Difference ◽  
P Value ◽  
Free Survival ◽  
Mantle Cell

Abstract Introduction: Rituximab plus chemotherapy has been proved to be the standard in treating advanced follicular lymphoma. However in mantle cell lymphoma (MCL) the results are still controversial. Methods: In a prospective randomised trial (OSHO#39) we compared the efficacy and toxicity of MCP chemotherapy(mitoxantrone 8 mg/m2 d 1+2, chlormabucil 3x3 mg/m2 d 1–5 and prednisolone 25 mg/m2 d q 4 weeks)versus MCP plus rituximab (375 mg/m2 d -1) in advanced indolent lymphoma and mantle cell lymphoma. Here we present the results of the MCL subgroup (n=90) among the 358 randomised patients (FL, MCL, LPL). Study endpoints included overall and complete response rate (RR + CR), progression free survival (PFS), event free survival (EFS), overall survival (OS) and toxicities. Results: with a median follow-up of 43 months for the MCL subgroup we can provide relatively mature data. Concerning toxicities there was no striking difference between the treatment groups. The treatment results for the MCL patients are as follows: Conclusions: Concerning all end-points R-MCP is not superior to MCP chemotherapy alone in advanced mantle cell lymphoma. Immunochemotherapy is obviously not the solution for this poor prognosis lymphoma entity. Results R-MCP n=44 MCP n=46 p-value Response Rate 70,5% 63% .5074 Complete Responses 31,8% 15,2% .0822 PFS median 20,5 months 19 months .2482 PFS 42 months 31% 14% EFS median 19 months 14 months .1369 EFS 42 months 27% 11,5% OS median 56 months 50 months .4862 OS 42 months 60% 61%

Vorinostat (SAHA), Cladribine, and Rituximab in Previously Untreated Mantle Cell Lymphoma: Updated Results From a Phase I/II Trial

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3675-3675 ◽  
Author(s):  
Stephen E Spurgeon ◽  
Kamal Sharma ◽  
David F. Claxton ◽  
Christopher W. Ehmann ◽  
Carla Gallagher ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Phase Ii ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Significant Activity ◽  
Free Survival ◽  
Mantle Cell ◽  
Upregulated Genes

Abstract Abstract 3675 Background: Mantle cell lymphoma (MCL) remains incurable and little consensus exists on the best standard initial therapy. However, improved understanding of disease biology has the potential to lead to novel treatment approaches including new perspectives on older drugs. For example, epigenetic modifications including altered DNA methylation and histone acetylation previously identified in MCL has provided the rationale for using the combination of a hypomethylating agent and a histone deactylase inhibitor. Here we show that agents with differing mechanisms have significant activity in previously untreated MCL. In addition to its cytotoxic effects in lymphoid malignancies, cladribine has hypomethylating properties. Vorinostat (SAHA) is a histone deacetylase inhibitor (HDACi) FDA approved in cutaneous T cell lymphoma with modest single agent activity in MCL. Preclinically, the combination of these agents has been shown to activate silenced genes. Since cladribine inhibits DNA methylation via a unique mechanism, it could also potentially inhibit histone methylation. We previously reported initial results of our Phase I/II trial combining SAHA, cladribine, and rituximab (SCR) for the treatment of B-cell non-Hodgkin's Lymphoma (NHL) [Spurgeon et al, ASH, 2012]. Here we present the updated results from the Phase II portion of the trial in the untreated MCL cohort including response rate, overall and progression free survival, and correlative studies. Methods: The achieved phase II starting dose was vorinostat 400 mg po (days 1–14) combined with cladribine 5mg/m2 IV (days 1–5), and Rituximab 375 mg/m2 IV (weekly × 4 for cycle 1 and 1x/month) every 28 days for up to 6 cycles. Response evaluation occurs after 2 cycles and at the completion of therapy. Responding patients are eligible to receive maintenance rituximab. Phase II eligibility includes relapsed NHL as well as previously untreated MCL. The primary outcome is response rate (ORR); secondary endpoints include progression-free survival (PFS) and overall survival (OS). Scientific correlatives include analysis of CD20 expression, histone acetylation, gene microarray, qRT-PCR and HELP methylation analysis. To evaluate the possible effects of SAHA metabolism on toxicity and response, UDP-glucuronosyltransferase 2B17 (UGT2B17) genotyping is also performed. This study continues to enroll patients. Results: 28 previously untreated MCL patients have been enrolled on the phase II portion of the study. 7 have not yet completed the planned 6 cycles; however, 26 patients have completed ≥ 2 cycles and are evaluable for response. The majority of responding patients have received maintenance rituximab. The overall response rate (ORR) is 100% (26/26) with 69% (18/26) achieving CR. Of those patients not attaining CR, 2 had blastic MCL and died, 3 have not yet completed active treatment, and 1 withdrew consent after two cycles. At a median follow up of 14.7 months (.07 – 25 months) 4 patients have relapsed and 3 have died. Of the relapsing patients, two had blastic MCL. None of the patients achieving a CR has relapsed. The estimated PFS curve (shown in the Kaplan-Meier curve below) did not reach the 0.5 level and therefore, median PFS could not be estimated. Toxicities were defined using CTCAE 4 and primarily include neutropenia, thrombocytopenia, fatigue, anorexia, and dehydration. We found that cladribine hypomethylates DNA in vivo (8/8 pts) and inhibits histone methylation in vitro. There were no upregulated genes common to untreated leukemic MCL patients; however, a number of changes in gene expression were observed. For example, upregulated genes after treatment included DUSP2 (3 patients), FOXO3 (2 patients), NOXA1 (2 patients), CEBPb (2 patients) and p53 (3 patients). Conclusions: The SCR regimen has significant activity and shows epigenetic activity in previously untreated MCL. Initial follow up results are promising, especially in patients without blastic MCL who continue with maintenance rituximab. The SCR regimen should be studied further in NHL. Disclosures: Spurgeon: Merck : Research Funding. Off Label Use: vorinostat: off label use mantle cell lymphoma. Epner:Merck: Research Funding, Speakers Bureau.

Sign in / Sign up

Export Citation Format

Share Document