Phase 3 LyMa Trial: Rituximab After ASCT Improves OS in Mantle Cell Lymphoma

Minimal residual disease is a major cause of relapse in patients treated for mantle cell lymphoma (MCL), which is a less common form of non-Hodgkin’s lymphoma. While maintenance therapy with rituximab (RM) following R-CHOP (which includes rituximab, cyclophosphamide, doxorubicin, hydrochloride, vincristine sulphate, and prednisone) has been shown to improve overall survival (OS) in older patients, its impact on OS in young patients following autologous stem cell transplant (ASCT) has not yet been evaluated.

Now, phase 3 results from the LyMa trial have shown that RM after ASCT prolongs event-free survival (EFS), progression-free survival (PFS), and OS in previously untreated young patients with MCL following ASCT. The results were presented during a session, Therapeutic Approach to Mantle Cell Lymphoma, by Steven Le Gouill, MD, PhD, from the Department of Hematology, Nantes University Hospital and UMR892 INSERM, of Nantes, France, at the 58th American Society of Hematology Annual Meeting & Exposition, being held December 3-6, in San Diego, California. Le Gouill said that this was the first time that the final results of the LyMa trial were being shared.

Between September 2008 and August 2012, the trial enrolled 299 treatment-naïve individuals diagnosed with MCL. Inclusion criteria included diagnosis of MCL, presence of the t(11;14) translocation, untreated MCL patients with at least 1 tumor site for assessment, aged between 18 and 65 years, and informed consent to participate in the trial. Patients were excluded from participation if they were diagnosed with another type of lymphoma besides MCL, if they were in relapse, positive for HIV or hepatitis B or C, or had uncontrolled diabetes.

Induction immuno-chemotherapy consisted of 4 courses of R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and salt platinum) every 21 days, followed by ASCT consolidation. Of the 277 patients who received 4 courses of R-DHAP and 20 who received R-CHOP, 257 underwent ASCT. Patients who did not respond after R-DHAP received 4 additional courses of R-CHOP-14 before ASCT (n = 20). The conditioning regimen for ASCT was R-BEAM (rituximab, BICNU, etoposide, ara-C, and melphalan). Patients who responded to ASCT were randomized to receive RM (1 infusion of 375 mg/m² every 2 months for 3 years) or not (120 in each cohort).

Of the 257 patients who responded to ASCT, 240 were then randomized (1:1) to receive RM or not. The median follow-up was 54.4 months following inclusion (range, 52.7-59.2) and 50.2 months following randomization (range, 46.5-54.2). The primary endpoint was EFS, calculated from the time of randomization, with events defined as disease progression, relapse, death, severe infection, or allergy to rituximab. Secondary endpoints were PFS and OS from time of diagnosis and time of randomization.

The 4-year PFS was 67.8% (95% CI, 62.1 to 72.8) and OS was 78% (95% CI; 72.8 to 82.3). According to EFS definition, 47 (39.2%) patients had an event in the no RM versus 25 (20.8%) in the RM arm. The mEFS from randomization was not reached in either arm. The 4 year-EFS was 61.4% (95% CI, 51.3 to 69.9) in the no RM arm vs 78.9% (95% CI, 69.6 to 85.6) in the RM arm (P = .0012). The EFS duration was significantly superior in the RM arm with a 54.3% reduction in the risk of event (hazard ratio [HR]= .457; 95% CI, 0.28 to 0.74; P = .0016). The median PFS and OS from randomization were not reached in both arms. The 4 year-PFS from randomization was higher in the RM arm: 82.2% (95% CI, 73.2 to 88.4) vs 64.6% (95% CI, 54.6 to 73) (P = .0005), as was the 4-year OS: 88.7% (95% CI, 80.7 to 93.5) vs 81.4% (95% CI, 72.3 to 87.7; P = .0413). Patients in the RM arm had a 60% reduction of risk of progression (HR=0.4; 95% CI, 0.23 to 0.68; P = .0007) and a 50% reduction of risk of death (HR = 0.5; 95% CI, 0.25 to 0.98; P = .0454).

Based on their trial results, Le Gouill concluded, “Rituximab maintenance dose of 375 mg/m² every 2 months for 3 years is recommended in transplanted MCL patients.”

Reference

Le Gouill S, Thieblemont C, Oberic L, et al. Rituximab maintenance after ASCT prolongs survival in younger patients with mantle cell: phase 3 LyMa trial of the Lysa/Goelams group. Presented at the 58th American Society of Hematology Annual Meeting & Exposition, San Diego, California, December 3, 2016. Abstract 145.