The addition of BTK inhibitor ibrutinib with and following autologous hematopoietic stem cell transplantation (autoHCT) showed tolerability and may improve progression-free survival (PFS) among patients with relapsed/refractory (R/R) activated B-cell subtype diffuse large B-cell lymphoma (ABC-DLBCL), according to a primary analysis of a phase 3 trial. 

Charalambos Andreadis, MD, Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, California, and coauthors presented the data from this trial at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, California. 

According to Dr Andreadis and coauthors, “AutoHCT is an effective therapy for patients with DLBCL who are refractory or relapse following first-line chemotherapy, but long-term outcomes remain suboptimal.” To assess more optimal therapies for this patient population, the study authors aimed to examine the efficacy and safety of adding ibrutinib to autoHCT as part of conditioning and as a consolidation therapy in this trial. The primary end point was the 2-year PFS. 

In this study, eligible patients with high risk features, including chemotherapy-sensitive persistent or relapsed ABC-DLBCL, who received ≤3 prior regimens, had no active central nervous system involvement, no need for long-term anticoagulation, and no prior progression on ibrutinib, were enrolled. 

Patients were randomly assigned to receive either ibrutinib at 560 mg in arm A, or placebo in arm B, simultaneously with conditioning of days -6 to -1 of autoHCT. Patients continued this regimen for 12 additional 28-day cycles. Patients with disease progression in arm B were permitted to crossover to arm A and use single-agent ibrutinib. For disease confirmation and subtype assignment, a central pathology review was assessed. 

Among all patients enrolled, 87% of patients in arm A and 88% in arm B underwent conditioning, while 70% of arm A and 67% of arm B started maintenance therapy. Patients in arm A received a median of 6 cycles, and patients in arm B received a median of 5 cycles. The 2-year PFS was 57.6% (95% confidence interval [CI]) in arm A compared to 40.8% (95% CI) in arm B. In arm A, the median PFS was 26.5 months, compared to 8.1 months in arm B. In arm B, 1 patient crossed over to arm A. 

In terms of safety, the most common grade 3 to 4 adverse events in arms A and B were neutropenia (A: 14%, B: 14%), febrile neutropenia (A: 11%, B: 9%), and thrombocytopenia (A: 11%, B: 7%). The rate of atrial fibrillation at any grade was comparable across arms, but both patients with grade 3 (n = 1) and grade 4 (n = 1) atrial fibrillation were in arm B. Grade 5 events were observed in 6 patients, but only 1 grade 5 event was considered correlated with treatment. 

Dr Andreadis and coauthors concluded, “Despite an early high rate of screen failures and declining accruals due to competition with [chimeric antigen receptor] (CAR)-T cell therapy, the primary analysis suggests that ibrutinib with and following AutoHCT in relapsed/refractory ABC-DLBCL is well-tolerated and may improve PFS in this high-risk patient population.”

Source:

Andreadis C, Bobek C, Hsi ED, et al. Ibrutinib added to standard conditioning and as consolidation therapy following autologous hematopoietic stem cell transplantation (autoHCT) for relapsed/refractory activated-b-cell subtype diffuse large b-cell lymphoma (ABC-DLBCL): primary analysis of the US intergroup double-blind randomized phase III study alliance A051301/BMT-CTN 1201. Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 437