Journal Article

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

Weigert, Oliver, Greiner, Jochen, Dreyling, Martin, Fischer, Luca, Hiddemann, Wolfgang, Stilgenbauer, Stephan, Unterhalt, Michael, Macro, Margaret, Giagounidis, Aristoteles A. N., Durot, Eric, de Wit, Maike, Delwail, Vincent, Silkenstedt, Elisabeth, Hoffmann, Martin, Ribrag, Vincent, Feugier, Pierre, Jiang, Linmiao, Klapper, Wolfram, Scholz, Christian W., Hallek, Michael, Hoster, Eva, Schmidt, Christian, Solal-Celigny, Philippe, Graeven, Ullrich, Foussard, Charles, Trappe, Ralf Ulrich, Dürig, Jan, Hänel, Mathias, Bouabdallah, Krimo, Dargel, Beate, Pott, Christiane

2024

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/67/1059/602 / 692/699/1541/1990/291/1621/1915 / Adult / Aged / Aged, 80 and over / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Bortezomib / Bortezomib - administration & dosage / Bortezomib - therapeutic use / Cancer Research / Chemotherapy / Critical Care Medicine / Cytarabine / Cytarabine - administration & dosage / Cytarabine - therapeutic use / Dexamethasone / Dexamethasone - administration & dosage / Dexamethasone - adverse effects / Dexamethasone - therapeutic use / Drug Resistance, Neoplasm / Female / Follow-Up Studies / Hematology / Humans / Immunotherapy / Inhibitor drugs / Intensive / Internal Medicine / Labels / Leukopenia / Lymphoma / Lymphoma, Mantle-Cell - drug therapy / Lymphoma, Mantle-Cell - mortality / Lymphoma, Mantle-Cell - pathology / Lymphopenia / Male / Mantle cell lymphoma / Medicine / Medicine & Public Health / Middle Aged / Monoclonal antibodies / Neoplasm Recurrence, Local - drug therapy / Neoplasm Recurrence, Local - pathology / Oncology / Patients / Response rates / Rituximab / Rituximab - administration & dosage / Rituximab - therapeutic use / Stem cell transplantation / Stem cells / Subgroups / Survival / Survival Rate / Targeted cancer therapy / Toxicity