SUMMARY: The American Cancer Society estimates that in 2017, about 72,240 people will be diagnosed with Non Hodgkin Lymphoma (NHL) in the United States and about 20,140 individuals will die of this disease. Mantle Cell Lymphomas (MCL) account for approximately 6% of all Non Hodgkin Lymphomas in adults and have a high relapse rate following dose-intensive therapies. Early and late relapses in patients with MCL have been attributed to persistence of residual disease. Maintenance therapy with RITUXAN® (Rituximab) following induction chemotherapy with R-CHOP, prolonged remission and significantly improved Overall Survival in elderly patients with MCL (N Engl J Med. 2012;367:520-531). The role of maintenance RITUXAN® and its impact on Overall Survival in young patients following Autologous Stem Cell Transplant (ASCT) has however not been investigated.
The LyMa trial is a prospective, international, randomized, phase III study that evaluated the benefit of RITUXAN® maintenance following ASCT, in young previously untreated MCL patients. This study enrolled 299 treatment-naïve MCL patients, diagnosed according to WHO 2008 classification, with a median age of 57 years, of whom 277 patients (N=277) were included in the study. Induction chemotherapy consisted of 4 cycles of R-DHAP (RITUXAN®, Dexamethasone, High dose Ara-C, Cisplatin) given every 3 weeks followed by ASCT. Patients who did not respond to R-DHAP received 4 additional courses of R-CHOP-14 before undergoing ASCT (N=20). The conditioning regimen for ASCT was R-BEAM (RITUXAN® BiCNU, Etoposide, Ara-C, and Melphalan). Following ASCT, 240 patients who responded, were randomized in a 1:1 ratio to receive RITUXAN® maintenance at 375 mg/m2 every 2 months for 3 years or no maintenance treatment. The Primary endpoint was Event Free Survival (EFS) calculated from time of randomization and these events included disease progression, relapse, death, severe infection or allergy to RITUXAN®. Secondary endpoints included Progression Free Survival and Overall Survival from time of diagnosis and time of randomization.
In the final analysis, the 4-year Event Free Survival (EFS) was 78.9% with RITUXAN® maintenance compared with 61.4% for those who did not get maintenance therapy (P=0.0012). The EFS duration was significantly superior in the RITUXAN® maintenance arm with a 54% reduction in the risk of events (HR=0.46; P=0.0016). The 4-year Progression Free Survival was 82.2% versus 64.6% with and without RITUXAN® maintenance, respectively (P=0.0005). The Overall Survival at 4 years was 88.7% and 81.4%, for RITUXAN® maintenance and no maintenance respectively (P=0.04). Patients in the RITUXAN® maintenance group had a 60% reduction in the risk of progression (HR=0.40; P=0.0007) and a 50% reduction in the risk of death (HR=0.50; P=0.05).
The authors concluded that RITUXAN® maintenance after ASCT prolongs Event Free Survival, Progression Free Survival and Overall Survival and is a new standard of care for young Mantle Cell Lymphoma patients. Rituximab Maintenance after Autologous Stem Cell Transplantation Prolongs Survival in Younger Patients with Mantle Cell Lymphoma: Final Results of the Randomized Phase 3 LyMa Trial of the Lysa/Goelams Group. Le Gouill S, Thieblemont C, Oberic L, et al. Presented at: 58th American Society of Hematology Annual Meeting & Exposition; December 3, 2016; San Diego, CA. Abstract 145.
