Brentuximab Vedotin and Ibrutinib Combination Fails to Provide Safety Among Patients With R/R Hodgkin Lymphoma

Despite the combination of brentuximab vedotin and ibrutinib demonstrating activity among patients with relapsed/refractory (R/R) Hodgkin lymphoma, this therapeutic regimen cannot be recommended for future development given notable toxicity, according to results from a multicenter phase 2 trial.

“As we previously observed preclinical synergy between ibrutinib and [brentuximab vedotin], we hypothesized ibrutinib may enhance the antitumor activity of [brentuximab vedotin] in [Hodgkin lymphoma],” Matthew Mei, MD, City of Hope National Medical Center, Duarte, California, and colleagues explained.

This multicenter, phase 2 trial included 39 participants aged ≥ 15 years with R/R Hodgkin lymphoma following at least 1 prior line of therapy. It was noted that 38% of patients had extranodal disease at baseline, 51% had advanced stage disease, 51% were refractory to the prior therapy, and 21% had prior brentuximab vedotin treatment.

Treatment consisted of brentuximab vedotin at 1.8 mg/kg administered intravenously every 3 weeks and ibrutinib at 560 mg taken daily by mouth (420 mg orally daily in the lead-in cohort). Investigators noted that prior brentuximab vedotin was allowed if patients were not refractory. The primary end point was the complete response (CR) rate, according to Lugano 2014. Secondary end points included toxicities, overall response rate (ORR), and duration of response (DOR).

Trial results demonstrated that of the 36 patients who were evaluable for response, the CR rate was 33% and the ORR 64%, with a median DOR of 25.5 months. Investigators noted that 13 patients proceeded to autologous transplant and 3 patients proceeded to allogeneic transplant for consolidation after response.

The most common adverse events were nausea (67%), peripheral neuropathy (62%), diarrhea (59%), fatigue (46%), thrombocytopenia (46%), headache (41%), rash (41%), elevated alanine transaminase (38%), anemia (36%), vomiting (36%), abdominal pain (33%), fever (33%), and hypertension (33%). Additionally, 6 patients experienced unacceptable toxicity—which was defined as grade 3 or 4 non-hematologic toxicity or non-resolving grade 3 or 4 hematologic toxicity—including 1 patient who died of multi-organ failure from suspected COVID-19 infection during cycle 1.

Mei and colleagues concluded, “The combination of [brentuximab vedotin] and ibrutinib was active in [R/R Hodgkin lymphoma]; however, given significant toxicity, it cannot be recommended for future development.”

Source:

Mei M, Tsai N-C, Palmer J, et al. Brentuximab vedotin plus ibrutinib in relapsed and refractory hodgkin lymphoma. Clin Lymph, Myeloma, Leuk. Published online April 10, 2024. doi: 10.1016/j.clml.2024.03.013