A study presented by Ida Wong-Sefidan, MD, of the University of California, San Diego, and colleagues at the 2026 ASCO Annual Meeting found that adding ibrutinib to R-da-EPOCH (dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) for patients with HIV-related diffuse large B-cell lymphoma may offer comparable or better survival outcomes compared with R-da-EPOCH alone.
Because HIV subverts interleukin-2-inducible T-cell kinase during replication, the researchers thought that adding the Bruton’s tyrosine kinase inhibitor ibrutinib may confer clinical benefit in this patient population.
The multicenter study incorporated a 3+3 dose de-escalation design followed by dose-expansion at the recommended phase 2 dose of ibrutinib 560 mg daily. The study included adults with stage 2-4 HIV-related DLBCL who were treatment-naïve or had previously received one cycle of R-da-EPOCH or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).
A total of 43 patients were included in the safety analysis and 37 in the efficacy analysis (median age at baseline, 52 years; 81% male; 49% Black). Most patients (95%) tolerated two or more cycles of treatment, with a median of five cycles administered.
The overall response rate was 100%, with 57% complete responses and 43% partial responses. Relapse or disease progression occurred in 16.0% of patients during a median follow-up of 4.2 years, and the median duration of response was 2.8 years.
Three-year event-free survival and overall survival were 83% and 81%, respectively. The EFS and OS rates were comparable or higher than prior studies of R-da-EPOCH alone in this HIV-related DLBCL cohort, according to the researchers. Among patients with germinal center B-cell like DLBCL (60% of the cohort), the EFS and OS were 88% and 87%, respectively.
The researchers also noted that adverse events associated with this combination were manageable and typical of R-da-EPOCH. The most common treatment-related adverse events were anemia (50%), thrombocytopenia (41%), neutropenia (88%), and lymphopenia (68%); common non-hematologic adverse events were diarrhea, nausea, hypokalemia, fatigue, and sepsis.
Ten patients discontinued treatment due to withdrawal (n=4), treatment-related adverse events (n=4), progression (n=1), and lost to follow-up (n=1).
Reference
Wong-Sefidan I, Kwon D, Ambinder RF, et al. Integrating BTK inhibition into R-da-EPOCH for HIV-related DLBCL. Abstract #7001. Presented at the 2026 American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2026; Chicago.
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