According to results from the phase III phase III LyMa trial published in the <em>New England Journal of Medicine, </em>survival was improved for patients with mantle cell lymphoma with maintenance rituximab (Rituxan) following autologous stem-cell transplantation (ASCT).
Steven Le Gouill, MD, PhD
Steven Le Gouill, MD, PhD
According to results from the phase III phase III LyMa trial published in theNew England Journal of Medicine,survival was improved for patients with mantle cell lymphoma with maintenance rituximab (Rituxan) following autologous stem-cell transplantation (ASCT).
In the study, patients with MCL younger than 66 years assigned to maintenance therapy after ASCT had superior 4-year overall survival (OS; 89% vs 80%) and progression-free survival (PFS; 83% vs 64%;P<.001), compared with patients assigned to observation. Four-year event-free survival (EFS) also favored the experimental arm (79% vs 61%;P= .001). Cox regression unadjusted analysis also showed that the rate of 4-year OS favored rituximab (hazard ratio [HR], 0.50; 95% CI, 0.26-0.99;P= .04).
“An induction regimen with four courses of R-DHAP [(rituximab, dexamethasone, cytarabine, and a platinum derivative)] followed by transplantation without total-body irradiation resulted in a high rate of complete response. A 3-year course of rituximab maintenance therapy administered every 2 months prolonged overall survival among young patients with mantle cell lymphoma,” lead author Steven Le Gouill, MD, PhD, Nantes Medical University, and coinvestigators wrote.
“These results show the efficacy of a cytarabine-based induction regimen free of anthracycline or alkylating agents in patients with this condition,” added Le Gouill et al.
While patients with MCL demonstrate high rates of complete response following immediate immunochemotherapy after transplantation, investigators with the Lymphoma Study Association Group noted that relapse is common. They sought to determine whether maintenance therapy with rituximab could prolong duration of response.
From September 2008 to August 2012, 299 patients were enrolled in the study. Of those patients, 279 received induction chemotherapy with 4 courses of DHAP repeated every 21 days. The overall response rate after induction therapy was 94%, including 124 complete responses (41%) and unconfirmed complete response in 107 (36%). The main reasons to stop treatment during induction therapy were disease progression (n = 5) and toxic effects (n = 7).
Of the patients who received induction, 257 underwent ASCT. After transplantation, 168 of 257 patients (65%) had a complete remission, and 61 (24%) had an unconfirmed complete remission.
A total of 240 patients who received ASCT underwent randomization, comprising the intent-to-treat population. There were 120 patients randomly assigned to rituximab maintenance and 120 assigned to observation. Patients in the rituximab group received maintenance therapy at a dose of 375 mg/m2 administered every 2 months for 3 years after transplantation.
At the July 1, 2015, stopping date, the median follow-up from inclusion was 54.4 months and the median follow-up from randomization was 50.2 months. The median PFS and median OS, as calculated from inclusion, were not reached in the included-patient population. Similarly, median PFS and median OS were not reached in low- and intermediate-risk patients. Among high-risk patients, the median PFS was 47.4 months and the median OS was 56.2 months (P<.001 for both compared to the low-risk group).
The median EFS from randomization was not reached in either the rituximab group or the observation group. As calculated from randomization, 4-year EFS was 79% (95% CI, 70-86) in the rituximab group compared with 61% (95% CI, 51-70) in the observation group (P= .001). HR for disease progression, relapse, death, rituximab allergy, or severe infection was 0.46 (95% CI, 0.28-0.74;P= .002).
Neither group reached median PFS or median OS from randomization. The 4-year PFS favored the rituximab group, 83% versus 64% (HR for disease progression, relapse, or death, 0.40; 95% CI, 0.23-0.68;P<.001). Four-year OS also favored the rituximab group, 89% versus 80% (HR for death, 0.50; 95% CI, 0.26-0.99;P= .04).
Le Gouill S, Thieblemont C, Oberic L, et al. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma.N Engl J Med.2017;377(13):1250-1260. doi:10.1056/NEJMoa1701769.