RESEARCH SUMMARY

Ibrutinib Plus R-da-EPOCH Shows Manageable Toxicity in HIV-Related DLBCL

Edited by:
Anthony Calabro, MA

Key Highlights

  • Ibrutinib 560 mg daily was identified as the recommended phase 2 dose when added to R-da-EPOCH in HIV-related DLBCL.
  • Among 37 response-evaluable patients, the overall response rate was 100%, including complete response in 57% and partial response in 43%; PET was optional.
  • At a median follow-up of 4.2 years, 3-year event-free survival and overall survival were 83% and 81%, respectively.
  • The most frequent treatment-related adverse events were hematologic, including anemia, thrombocytopenia, neutropenia, and lymphopenia.

Adding ibrutinib to rituximab with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin showed manageable toxicity and clinical activity in patients with HIV-related diffuse large B-cell lymphoma (DLBCL), according to findings published in the Journal of Clinical Oncology as a 2026 American Society of Clinical Oncology annual meeting abstract.

The researchers noted that HIV-related DLBCL is clinically and molecularly heterogeneous and that R-da-EPOCH is accepted as a standard of care in this population. The study evaluated the safety, feasibility, and activity of adding the Bruton tyrosine kinase inhibitor ibrutinib to R-da-EPOCH, with an effort to enrich for non-germinal center B-cell subtype and assess associations between lymphoma cell of origin and response.

The multicenter study included a 3+3 dose de-escalation cohort followed by dose expansion at the recommended phase 2 dose. Eligible patients were aged 18 to 64 years and had stage II to IV HIV-related DLBCL. Patients were either untreated or had received 1 cycle of R-da-EPOCH or CHOP off study. Patients with CD4 counts less than 100 and those with asymptomatic leptomeningeal disease were allowed.

Ibrutinib was administered daily on days 1 through 21, and R-da-EPOCH was administered for 6 total cycles. Moderate and strong CYP3A4 inhibitors were excluded due to potential interactions with ibrutinib and chemotherapy.

Study Findings

A total of 43 patients were evaluable for toxicity, and 37 were evaluable for response. Among the toxicity-evaluable population, 41 patients tolerated at least 2 cycles, and the median number of study therapy cycles received was 5. At baseline, the median age was 52 years, the median CD4 count was 204, and 9 patients had a CD4 count below 100. Most patients had stage III or IV disease, and 40% had non-germinal center B-cell subtype.

The recommended phase 2 dose of ibrutinib was 560 mg daily. Among response-evaluable patients, the overall response rate was 100%, with complete responses in 21 of 37 patients and partial responses in 16 of 37 patients. The researchers noted that PET was optional.

Relapse or progression occurred in 6 of 37 patients during a median follow-up of 4.2 years. Median response duration was 2.8 years. Three-year event-free survival and overall survival were 83% and 81%, respectively. Among patients with germinal center B-cell disease, 3-year event-free and overall survival were 88% and 87%, respectively; among those with non-germinal center B-cell disease, they were 76% and 63%, respectively.

Among 679 treatment-related adverse events, the most frequent were anemia, thrombocytopenia, neutropenia, and lymphopenia. Nonhematologic treatment-related adverse events included diarrhea, nausea, hypokalemia, fatigue, and sepsis. Reasons for treatment discontinuation included progression, withdrawal, treatment-related adverse events, and loss to follow-up.

Clinical Implications

According to the study authors, incorporating ibrutinib 560 mg daily with R-da-EPOCH in HIV-related DLBCL resulted in manageable toxicities typical of R-da-EPOCH. They also reported that, despite a lower confirmed complete response rate, 3-year event-free survival and overall survival were comparable with or higher than those reported in prior studies of R-da-EPOCH in HIV-related DLBCL.

The results specify that response was assessed in 37 patients and that PET was optional, both of which are important context when interpreting the response data.

Expert Commentary

“Incorporating ibrutinib 560mg daily with R-da-EPOCH in HIV-related DLBCL treatment resulted in manageable toxicities typical of R-da-EPOCH,” the researchers concluded.

Reference
Wong-Sefidan I, Kwon D, Ambinder RF, et al. Integrating BTK inhibition into R-da-EPOCH for HIV-related DLBCL. J Clin Oncol. 2026;44(suppl 16):7001. doi:10.1200/JCO.2026.44.16_suppl.7001