Replacing Autologous Stem Cell Transplant in Mantle Cell Lymphoma?

Prior phase 3 trials established autologous stem cell transplant (ASCT) consolidation and maintenance rituximab as standards of care in younger, transplant-eligible patients with previously untreated mantle cell lymphoma (MCL). Now, investigators report a multinational, industry-sponsored, phase 3 trial testing incorporation of the Bruton tyrosine kinase inhibitor (BTKi) ibrutinib into induction and maintenance therapy.

A total of 870 patients (median age, 57 years; 76% male; 98% white) were randomized to one of three regimens:

• Six alternating cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP), followed by ASCT consolidation in responding patients (arm A)
• The above regimen plus ibrutinib added to R-CHOP cycles and 2 years of ibrutinib maintenance therapy, with ASCT for responding patients (arm A+I)
• The A+I regimen without ASCT (arm I)

Patients in all arms also could receive rituximab maintenance according to local guidelines.

At a median follow-up of 31 months, 3-year failure-free survival (FFS; the primary outcome) was superior for arm A+I compared with arm A (88% vs. 72%; hazard ratio, 0.52; P=0.0008). FFS favored arm I over arm A (86% vs. 72%) but the difference did not reach significance (HR, 1.77). Cumulative 3-year treatment failure rates were 21.9% in arm A, 60.0% in arm A+I, and 10.8% in arm I. Outcomes for patients with poor-risk mantle cell lymphoma international prognostic index (MIPI) scores and p53 overexpression were significantly improved in the ibrutinib-containing arms compared with arm A. Grade 3–5 toxicities were similar during induction therapy with and without ibrutinib; however, adverse hematologic and infectious events were higher during maintenance therapy in arm A+I.