Final Results of the RiPAD+C Regimen Including Velcade In Front Line Therapy for Elderly Patients with Mantle Cell Lymphoma. A Phase II Prospective Study of the GOELAMS Group.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2791-2791 ◽  
Author(s):  
Remy Gressin ◽  
Roch Houot ◽  
Mario Ojeda Uribe ◽  
Christiane Mounier ◽  
Krimo Bouabdallah ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
Elevated Serum ◽  
Current Phase ◽  
First Line ◽  
Chop Regimen ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mantle Cell

Abstract Abstract 2791 Introduction: Elderly mantle cell lymphoma (MCL) patients (pts) do not benefit from dose-intensive chemotherapy upfront.1 The GOELAMS group recently demonstrated that a regimen comprising Vincristine/Adriamycine/Dexamethasone plus Chlorambucil (VAD+C) was well tolerated, had a good efficacy/toxicity profile and induced similar PFS than R-CHOP (median PFS between 16 to 18 months2,3,4). Additionally, it has been shown that bortezomib (Velcade®), with or without Rituximab has efficacy in relapsed/refractory MCL patients5,6. These data prompted, our group to conducte a phase II prospective non randomized clinical trial evaluating the combination of Velcade plus Rituximab/Adriblastine/Dexamethasone/Chlorambucil (RiPAD+C) as a first line therapy for elderly MCL patients. Aims: To evaluate the overall response rate (ORR) and toxicity after 4 cycles of RiPAD+C regimen (main objective) and to evaluate prognostic factors for survival (secondary objective). Protocol: RiPAD+C : Rituximab 375 mg/m2 on d1 (and d8 for cycle 1); PS 341, Velcade® 1.3 mg/m2 on d1, 4, 8 and 11; Adriblastine 9mg/m2/d as a continuous infusion for 4 days; Dexamethasone 20 mgx2/d from d1 to d4; Chlorambucil 12 mg/d, d20 to d29. Repeat cycles every 35d. After 4 cycles, responding pts (Cheson 1999 criteria) received 2 additional cycles for a maximum of 6. Patients and methods: Inclusion criteria: All untreated elderly (65 to 80 years old) MCL patients (including blastoid forms) presenting with a stage II to IV disease with a good PS (ECOG<3) were eligible. Histologic samples were centrally reviewed and Ki67 expression was evaluated for each sample according to the European guidelines7. Results: Population: from June 2007 to December 2009, 39 pts were enrolled in the study with a majority of males (n=30). Median age at diagnosis was 72 years [65-80]. All patients had stage III/IV disease and PS was ≥2 in 5 cases (15%). Elevated serum LDH were observed in 47% of cases. According to the MIPI, 28 patients (80%) had an intermediate or high score. Eleven (30%) patients presented with a blastoid variant and Ki67 staining was superior to 30% in 12 cases (37%). Toxicity: A total of 195 courses have been performed. Fourteen hospitalization (median duration = 7 days [1 and 55]) due to toxicity were necessary involving 12 pts (34%). Seven pts (18%) experienced grade 3 peripheral neuropathy. ten (25%) pts required blood transfusions for a total of 8 red blood cells and 14 platelets transfusions. Response after 4 cycles: ORR was 80% (n=31) including 51% of CRs. Eight pts discontinued the treatment before reaching cycle 4, two of them for toxicity reasons. Six patients (15%) were refractory or in progression. Response after 6 cycles (n=25; 64%): ORR was 74% including 20 pts in CRs (59%). Survival: With a median follow-up of 24 months, 27 pts are still alive. Two pts died of toxicity (severe sepsis) and 10 pts progressed. The median PFS is 26 months and the median OS has not been reached yet. According to the MIPI score, no differences in PFS were between pts with low and int/high scores. Conversely, the recently described Goelams index2 stratified pts with a low score (normal LDH, Ki67≤26%, PS≤1, and no B symptoms) from patients with an int/high score (p=.055). Conclusion: The results of the current phase II trial indicate that the RiPAD+C regimen, integrating bortezomib, is feasible and well tolerated as a first line therapy in elderly MCL pts. Historical comparisons suggest that this regimen compares favourably to the classical R-CHOP regimen in terms of response rates and duration. Bibliography: 1 Romaguera JE et al, JCO 2005; 2 Gressin R et al., Haematological 2010; 3 Howard OM et al., JCO 2002; 4 Lenz G et al., Blood 2005; 5 Fisher RI et al., JCO 2006; 6 Goy A et al., JCO 2009; 7 Klapper W et al., Haematopathol 2009. Disclosures: Off Label Use: velcade is of label in France for the treatment of mantle cell lymphoma.

The EBMT Lymphoma Working Party-European Mantle Cell Lymphoma Network Consensus Project On The Role Of Autologous and Allogeneic Stem Cell Transplantation In Mantle Cell Lymphoma: Recommendations Applying The Delphi Procedure

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3405-3405 ◽  
Author(s):  
Stephen Paul Robinson ◽  
Paolo Corradini ◽  
Peter Dreger ◽  
Dolores Caballero ◽  
Christian H Geisler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Cell Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mantle Cell

Abstract Introduction The role of both autologous (autoSCT) and allogeneic stem cell transplantation (alloSCT) in the management of patients with mantle cell lymphoma (MCL) remains to be clarified. In the absence of prospective comparative trials decision making for clinicians remains challenging. We have conducted a consensus project to provide guidance on how stem cell transplantation should be employed in MCL. Methods This was a collaborative project between the Lymphoma Working Party of the EBMT and the European Mantle Cell Lymphoma Network. The RAND modified Delphi consensus procedure was used. 12 clinicians, recognized for their expertise in MCL, from both transplant and non-transplant centres contributed. A literature search was performed and consensus statements were formulated. Panel members ranked each statement. The statements were reviewed and modified and then a second round of ranking was performed. Results Consensus agreement was reached on the following statements: 1. Patients should be considered for transplant strategies based on their biological age and comorbidities and not just chronological age. 2. An autoSCT should be considered as the standard first line consolidation therapy in all patients considered suitable for high dose therapy. 3. First line induction therapy prior to SCT should incorporate high dose cytarabine and Rituximab based regimens. 4. Patients achieving either complete remission or partial remission following induction therapy should be considered for autoSCT. 5. Patients failing to achieve a PR or CR following induction therapy should not proceed directly to an autoSCT. 6. Patients undergoing an allogeneic SCT should receive reduced intensity conditioning regimens. There was consensus disagreeing with the following statement: Prognostic criteria are available that permit the identification of low risk patients in need of first line therapy who should be considered for non-transplant based treatment. There was partial consensus agreeing with the following statements: 1. Patients relapsing after an autoSCT should be considered for an allogeneic stem cell transplant following reinduction therapy.2. Patients with evidence of MRD relapse post alloSCT should, in the absence of graft versus host disease, be considered for rapid withdrawal of immunesuppression and donor lymphocyte infusions. There was a partial consensus disagreeing with the following statements: 1 Patients should receive Rituximab maintenance following first line autologous stem cell transplant. 2. There are sufficient prognostic criteria to identify patients who should undergo an allogeneic stem cell transplantation as first line consolidation. 3. In patients relapsing after non-transplant first line therapy there are sufficient prognostic criteria to determine whether autoSCT or alloSCT consolidation should be used. Finally there was no consensus with respect to the following statements. 1. Disease response to induction therapy prior to autoSCT should be assessed by PET scan. 2. Minimal residual disease (MRD) negativity is mandatory prior to autoSCT. 3. A TBI based regimen should be considered as the standard for conditioning prior to autoSCT. 4. Patients undergoing an autoSCT should receive in-vivo purging with Rituximab at the time of high dose conditioning therapy. 5. Patients with relapsed disease following non-transplant first line therapy should be considered for an autologous stem cell transplant to consolidate second (or higher) response. 6. Patients with relapsed disease following non-transplant first line therapy should be considered for an allogeneic SCT to consolidate second (or higher) response. 7. Patients undergoing autoSCT should be monitored for MRD post transplant. 8. Patients with evidence of MRD relapse post autoSCT should receive preemptive Rituximab. 9. Patients undergoing alloSCT should be monitored for MRD post transplant. Conclusions Consensus was obtained with regard to the role of autologous SCT in first line consolidation. However, the application of appropriate clinical and molecular prognostic factors to guide therapeutic decisions and the role of allogeneic transplantation warrant further clinical investigation. Disclosures: No relevant conflicts of interest to declare.

Lenalidomide, Bendamustine, and Rituximab As First-Line Therapy For Patients >65 Years With Mantle Cell Lymphoma: Preliminary Results From The Nordic Lymphoma Group MCL4 (LENA-BERIT) Phase I-II Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4377-4377 ◽  
Author(s):  
Mats Jerkeman ◽  
Alexandra Albertsson-Lindblad ◽  
Arne Kolstad ◽  
Anna Laurell ◽  
Riikka Räty ◽  
...  
Keyword(s):  
Phase I ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mantle Cell

Abstract Background Mantle cell lymphoma is a disease of the elderly, with a median age of 70 years. Younger patients may be treated with potentially curative treatment including high dose chemotherapy. For elderly patients, however, no standard therapy has been defined. In the current trial, we investigate if the addition of lenalidomide (LEN) to rituximab (R)+bendamustine (B) (B 90 mg/m2 D1-2 and R 375 mg/m2 D1) followed by maintenance with LEN for 7 months may enhance efficacy, with manageable toxicity, for the older population of MCL patients. Methods Eligibility criteria were age > 65 years, or ≤ 65 years, unable to tolerate high dose chemotherapy, with untreated mantle cell lymphoma, stage II-IV. BR was given for 6 cycles q4w. In the phase I part, the MTD of LEN was established as 10 mg days 1-14 during the induction phase, cycles 2-6. Prednisolone 20 mg days 1-14 was given during cycle 2. When LEN was initially given from cycle 1, we encountered unexpected grade III-IV toxicity in the form of cutaneous and allergic reactions. In the maintenance phase, LEN single therapy was given as follows: cycles 7-8 - 10 mg days 1-21, cycles 9-13 - 15 mg days 1-21. Results The trial was concluded June 1, 2013, after inclusion of 51 patients, of whom 24 were in the phase I part. The median age is 72 years. According to MIPI, 55% were high risk. Presently, 29 patients are evaluable for response after 6 cycles LBR. ORR is 28/29 (97%), CR+CRu 23 (79%). 17 out of 28 evaluable patients (61%) were MRD-negative after 6 cycles. After a median follow-up of 18 months, the median PFS has not been reached, and the estimated PFS at 2 years is 74%. Eight patients have died, 3 due disease progression, 3 due to treatment related toxicity, 1 of lung cancer in a heavy smoker, 1 of CMML. Overall survival at 2 years is 87%. Conclusions When omitted in cycle 1, lenalidomide in combination with R-bendamustine is feasible as first-line therapy in older patients with MCL, and is associated with a high response rate, also as assessed by MRD. The long term efficacy of this regimen remains to be established by longer follow-up. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Addition of rituximab to chemotherapy alone as first-line therapy improves overall survival in elderly patients with mantle cell lymphoma

Blood ◽  
2011 ◽  
Vol 118 (18) ◽  
pp. 4808-4816 ◽  
Author(s):  
Robert Griffiths ◽  
Joseph Mikhael ◽  
Michelle Gleeson ◽  
Mark Danese ◽  
Martin Dreyling
Keyword(s):  
Overall Survival ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Propensity Score Analysis ◽  
Average Length ◽  
First Line ◽  
Non Hodgkin Lymphoma ◽  
First Line Therapy ◽  
Score Analysis ◽  
Mantle Cell

Abstract Clinical trials have demonstrated that rituximab improves overall survival in non-Hodgkin lymphoma (NHL), except in mantle cell lymphoma (MCL). We used Surveillance Epidemiology and End Results (SEER)–Medicare data to compare survival in older MCL patients who began chemotherapy with or without rituximab within 180 days of diagnosis. Patients were followed from diagnosis (January 1999 to December 2005) until death or the end of observation (December 2007). Medicare administrative and claims data were used to identify the date and cause of death and the immunochemotherapy regimen. Of 638 patients, the mean age at diagnosis was 75 years, 75% had stage III/IV disease, 67% had extranodal involvement, and 64% received rituximab. The average length of first-line treatment was 21 weeks, with no difference between the 2 groups (P = .76). Median survival was 27 months for chemotherapy alone, compared with 37 months for chemotherapy plus rituximab (P < .001). In multivariate analysis of 2-year survival, rituximab plus chemotherapy was associated with lower all-cause (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.41-0.82; P < .01), and cancer-specific (HR 0.56; 95% CI 0.37-0.84; P < .01) mortality. Results were similar when using the entire observation period, propensity score analysis, and limiting chemotherapy to CHOP/CHOP-like. We conclude that first-line chemotherapy including rituximab is associated with significantly improved survival in older patients diagnosed with MCL.

Interim Results of the RiPAD+C Regimen Including Velcade in Front Line Therapy for Elderly Patients with Mantle Cell Lymphoma. A Phase II Prospective Study of the GOELAMS Group.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1575-1575
Author(s):  
Remy Gressin ◽  
Sylvie caulet Maugendre ◽  
Steven Le Gouill ◽  
Mario ojeda Uribe ◽  
Magda Alexis Vigier ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Mantle Cell Lymphoma ◽  
Phase Ii ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Therapeutic Option ◽  
Front Line ◽  
Good Efficacy ◽  
Line Therapy ◽  
Mantle Cell

Abstract Elderly patients with mantle cell lymphoma (MCL) do not take benefit from dose-intensive chemotherapy such as HyperCVAD because of its high toxicity (Romaguera JCO 2005). Prior Goelams clinical trials using the VAD plus Chlorambucil regimen with or without Rituximab have demonstrated a good efficacy/toxicity ratio in front line therapy (EHA 2008, a0259). Proteasome inhibitors are among the most promising new agents for relapsing patients (Fisher, JCO 2006). Therefore, the GOELAMS conducted a phase II clinical trial including Velcade plus R-AD and Chlorambucil (RiPAD + Chlorambucil) for elderly MCL patients upfront. Aims: To evaluate toxicity and overall response rate after 4 cycles of RiPAD + Chlorambucil regimen. Protocol: RiPAD + C: Rituximab 375 mg/sqm, D1 (and D8 for cycle 1); PS 341, Velcade 1.3 mg/sqm D1, 4, 8 and 11; Adriblastine 9mg/sqm/D in a 4 days continuous infusion; Dexamethasone 20 mgx2/D for D1 to D4; Chlorambucil 12 mg/D, D20 to D29. One cycles every 35 D. The patients received a maximum of 6 cycles. Inclusion criteria: Untreated MCL patients (from 65 to 80 years) with a stage II to IV disease, and good PS (Ecog &lt; 3). Response criteria is evaluated according to the 1999 Cheson’s criteria, all patients were also evaluated by FDG-PETscan. Results: since June 2007, 27 patients have been included. Thirteen have been evaluable after 4 cycles. Median age is 71 years (66–80 y). After 4 cycles, disease Status was: 10 patients in response (3 in CR with negative FDG-PETscan and 7 in PR including 3 with a negative PETscan) and 3 patients progressed on therapy. The 3 non responding patients had the highest Ki67 value over 30%. Toxicity evaluation has been evaluated based on 59 cycles. Grade 3–4 toxicities have been reported in 5 cases (2 neurologic, 1 hepatic, 1 cardiac and 1 pulmonary). Only 3 cycles were delayed because of toxic reasons. Conclusion: this intermediaire analysis shows an ORR of 77% (10/13) including 6 patients with a negative FDG-PET after only 4 cycles. Our study demonstrates that the RiPAD+C regimen has a good efficacy/toxicity ratio and is a promising therapeutic option for MCL elderly patients. The study is ongoing and additional results on response rate and toxicity will be updated for presentation in the ASH meeting.

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