1. 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.
- Author
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Fischer L, Jiang L, Dürig J, Schmidt C, Stilgenbauer S, Bouabdallah K, Solal-Celigny P, Scholz CW, Feugier P, de Wit M, Trappe RU, Hallek M, Graeven U, Hänel M, Hoffmann M, Delwail V, Macro M, Greiner J, Giagounidis AAN, Dargel B, Durot E, Foussard C, Silkenstedt E, Weigert O, Pott C, Klapper W, Hiddemann W, Unterhalt M, Hoster E, Ribrag V, and Dreyling M
- Subjects
- Humans, Female, Male, Aged, Middle Aged, Adult, Drug Resistance, Neoplasm, Survival Rate, Aged, 80 and over, Follow-Up Studies, Bortezomib administration & dosage, Bortezomib therapeutic use, Lymphoma, Mantle-Cell drug therapy, Lymphoma, Mantle-Cell pathology, Lymphoma, Mantle-Cell mortality, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Dexamethasone administration & dosage, Dexamethasone therapeutic use, Dexamethasone adverse effects, Cytarabine administration & dosage, Cytarabine therapeutic use, Rituximab administration & dosage, Rituximab therapeutic use, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology
- Abstract
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., (© 2024. The Author(s).)
- Published
- 2024
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