Obinutuzumab vs rituximab for transplant-eligible patients with mantle cell lymphoma.

ABSTRACT: Obinutuzumab (O) and rituximab (R) are 2 CD antibodies that have never been compared in a prospective randomized trial of mantle cell lymphoma (MCL). Herein, we report the long-term outcome of the LyMa-101 trial, in which newly diagnosed patients with MCL were treated with chemotherapy plus O before transplantation, followed by O maintenance (O group). We then compared these patients with those treated with the same treatment design with R instead of O (R group). A propensity score matching (PSM) was used to compare the 2 populations (O vs R groups) in terms of measurable residual disease (MRD) at the end of induction (EOI), progression-free survival (PFS), and overall survival (OS). In LyMa-101, the estimated 5-year PFS and OS after inclusion (n = 85) were 83.4% (95% confidence interval [CI], 73.5-89.8) and 86.9% (95% CI, 77.6-92.5), respectively. At EOI, patients treated in the O group had more frequent bone marrow MRD negativity than those treated in the R group (83.1% vs 63.4%; χ2, P = .007). PSM resulted in 2 sets of 82 patients with comparable characteristics at inclusion. From treatment initiation, the O group had a longer estimated 5-year PFS (P = .029; 82.8% vs 66.6%; hazard ratio [HR], 1.99; 95% confidence interval (CI), 1.05-3.76) and OS (P = .039; 86.4% vs 71.4%; HR, 2.08; 95% CI, 1.01-4.16) compared with the R group. Causes of death were comparable in the 2 groups, the most common cause being lymphoma. O before transplantation and in maintenance provides better disease control and enhances PFS and OS compared with R in transplant-eligible patients with MCL. These trials were registered at www.clinicaltrials.gov as #NCT00921414 and NCT02896582.

The addition of bortezomib to rituximab, high-dose cytarabine and dexamethasone in relapsed or refractory mantle cell lymphoma-a randomized, open-label phase III trial of the European mantle cell lymphoma network.

The therapy of relapsed or refractory (r/r) mantle cell lymphoma (MCL) patients remains a major clinical challenge to date. We conducted a randomized, open-label, parallel-group phase-III trial hypothesizing superior efficacy of rituximab, high-dose cytarabine and dexamethasone with bortezomib (R-HAD + B) versus without (R-HAD) in r/r MCL ineligible for or relapsed after autologous stem cell transplant (ASCT). Primary endpoint was time to treatment failure (TTF), secondary endpoints included response rates, progression free survival, overall survival, and safety. In total, 128 of 175 planned patients were randomized to R-HAD + B (n = 64) or R-HAD (n = 64). Median TTF was 12 vs. 2.6 months (p = 0.045, MIPI-adjusted HR 0.69; 95%CI 0.47-1.02). Overall and complete response rates were 63 vs. 45% (p = 0.049) and 42 vs. 19% (p = 0.0062). A significant treatment effect was seen in the subgroup of patients >65 years (aHR 0.48, 0.29-0.79) and without previous ASCT (aHR 0.52, 0.28-0.96). Toxicity was mostly hematological and attributable to the chemotherapeutic backbone. Grade ≥3 leukocytopenia and lymphocytopenia were more common in R-HAD + B without differences in severe infections between both arms. Bortezomib in combination with chemotherapy can be effective in r/r MCL and should be evaluated further as a therapeutic option, especially if therapy with BTK inhibitors is not an option. Trial registration: NCT01449344.