PS1259 LONG-TERM FOLLOW-UP OF JCOG0406 STUDY: INTENSIVE IMMUNOCHEMOTHERAPY (R-HIGH CHOP/CHASER) FOLLOWED BY HIGH-DOSE CHEMOTHERAPY (LEED) WITH AUTO-PBSCT IN UNTREATED MANTLE CELL LYMPHOMA

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.

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Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study

Annals of Oncology ◽

10.1093/annonc/mdt366 ◽

2013 ◽

Vol 24 (11) ◽

pp. 2892-2897 ◽

Cited By ~ 74

Author(s):

P.L. Zinzani ◽

J.M. Vose ◽

M.S. Czuczman ◽

C.B. Reeder ◽

C. Haioun ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

Subset Analysis ◽

Mantle Cell ◽

Long Term Follow Up

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Long-term follow-up of autologous stem cell transplantation in patients with diffuse mantle cell lymphoma in first disease remission

Cancer ◽

10.1002/cncr.11838 ◽

2003 ◽

Vol 98 (12) ◽

pp. 2630-2635 ◽

Cited By ~ 72

Author(s):

Issa F. Khouri ◽

Rima M. Saliba ◽

Grace-Julia Okoroji ◽

Sandra A. Acholonu ◽

Richard E. Champlin

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Mantle Cell Lymphoma ◽

Autologous Stem Cell Transplantation ◽

Cell Lymphoma ◽

Disease Remission ◽

Mantle Cell ◽

Long Term Follow Up

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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 ◽

10.1182/blood.v122.21.4377.4377 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4377-4377 ◽

Cited By ~ 9

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.

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The Combination of Weekly Infusion of Rituximab and Bortezomib Is Effective in Relapsed or Refractory Indolent and Mantle Cell Lymphoma: Long-Term Results of Phase II BRIL06 Study of the Fondazione Italiana Linfomi (FIL)

Blood ◽

10.1182/blood.v126.23.2735.2735 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2735-2735 ◽

Cited By ~ 2

Author(s):

Annalisa Chiappella ◽

Patrizia Pregno ◽

Pier Luigi Zinzani ◽

Amalia De Renzo ◽

Andrea Evangelista ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Phase Ii ◽

Cell Lymphoma ◽

Long Term Results ◽

High Dose ◽

Treatment Schedule ◽

Weekly Infusion ◽

Mantle Cell

Abstract Background. Bortezomib, an inhibitor of the proteasome, is effective in relapsed mantle cell lymphoma (MCL) and indolent lymphomas and it is synergistic with Rituximab to enhance apoptosis and NFkB depletion. On these basis, the FIL conducted a phase II multicenter study aimed to evaluate safety and efficacy of Bortezomib in association with Rituximab in relapsed/refractory non-follicular Lymphoma (Linfocytic, LL and Marginal Zone Lymphoma, MZL) and MCL, not eligible to high dose chemotherapy with stem cell transplantation. Patients and methods. The study was a prospective single arm phase II trial, designed on Simon two-stage Optimal Design. Primary end-point was to obtain an Overall Response Rate (ORR) > 40%. The aim of this analysis is to evaluate long term follow-up of Bortezomib and Rituximab combination. A central histological revision was planned in all the patients at the enrollment. Inclusion criteria were: 18-75 years, relapsed/refractory LL, MZL, MCL after 1-4 lines. Treatment schedule was: one course of 1.6 mg/sqm Bortezomib weekly in combination with standard 375 mg/sqm Rituximab on days 1, 8, 15, 22 followed by two courses of four weekly intravenous bolus of Bortezomib alone; patients with complete (CR), partial remission and stable disease at the intermediate evaluation were planned to be given three further courses with the same schedule. Results. From September 2006 to March 2008, 55 patients were enrolled and six were excluded at central histological revision. Clinical characteristics were: median age 68 (50-74); 16 (33%) LL, 8 (16%) MZL, 25 (51%) MCL; 42 (86%) stage III/IV; 33 (67%) bone marrow involvement. Median number of previous treatments was 2 (range 1-7); 34 (69%) were Rituximab pretreated; 21 (43%) had refractory disease. Thirty (61%) patients completed the treatment and 233 courses were delivered (median: 4.7 courses/patient); 19 (39%) patients did not because of no response in 13, adverse events in five, with only one toxic death due to interstitial pneumonia. ORR was 53% (CR 26.5%); no response was seen in 43% and 4% were not evaluable for response. ORRs by clinical subgroup were: LL 37%, MZL 50%, MCL 64%; Rituximab pretreated 62%, Rituximab naïve 33%; relapsed 64% and refractory 38%. With a median follow-up of 85 months, median Overall Survival (OS) was 61.5 months (95%CI: 35.0-81.5), with 5-years OS 51% (95% CI: 36-65) and median Progression Free Survival (PFS) was 8.9 months (95%CI: 5.3-18.3), with 5-years PFS 16% (95% CI: 7-28%). Five-years PFS by histology was: 12% (95% CI: 2-31) for LL, 17% (95% CI: 5-34) for MCL and 19% (95% CI: 11-53) for MZL. PFS rates were not different between Rituximab pretreated versus naïve nor international prognostic index 1-2 versus 3-4-5 nor refractory versus relapsed. By number of previous therapies, 5-years PFS for 1 previous therapy versus 2 versus 3 or more was: 24%, 14% and 13%, respectively, p=0.36. Conclusions. Weekly infusion of Bortezomib in combination with Rituximab is effective in relapsed/refractory indolent and MCL and represents a treatment option in this setting of patients. Disclosures No relevant conflicts of interest to declare.

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