Toxicities in Two Triplet Anti-CD20 Therapies for Follicular and Diffuse Large B-Cell Lymphomas

By Patrick Daly - Last Updated: February 24, 2022

A study published in the Journal of Cancer Research and Clinical Oncology discussed outcomes of anti-CD20-based combination therapy with obinutuzumab, atezolizumab, and polatuzumab vedotin (G-atezo-pola) in patients with relapsed refractory (R/R) follicular lymphoma (FL), and with rituximab, atezolizumab, and polatuzumab vedotin (R-atezo-pola) in patients with R/R diffuse large B-cell lymphoma (DLBCL). According to lead author, Max S. Topp, MD, and colleagues, no further development of either combination was planned due to recorded safety issues which they authors stated were “considered as related specifically to G-atezo-pola.”

The trial included 13 patients with FL and 23 patients with DLBCL. All patients with FL and all but two patients with DLBCL were treated and included in the final safety analysis. The primary efficacy endpoint was the rate of complete response (CR) at end of induction by PET-CT.

The median observation period was 23.3 months for the FL cohort and 5.7 months for DLBCL cohort. According to the report, “CR rates in FL patients treated with G-atezo-pola at polatuzumab vedotin doses of 1.4 mg/kg (n = 3) and 1.8 mg/kg (n = 7) were 33% and 14%, respectively,” at end of induction. Comparatively, the CR rate at end of induction in the patients with DBLCL receiving R-atezo-pola was 13%.

In the FL cohort, 62% of patients experienced a grade III to IV adverse event (AE), including two deaths, and 31% of patients developed a serious AE (SAE). R-atezo-pola in the DLBCL exhibited a lower incidence of grade III to IV AEs at 24%, including one death. The authors noted that hematologic toxicities were the most common grade III to IV AEs in both cohorts.

Ultimately, Dr. Topp and the study’s contributors deemed the safety profile of both triplet treatment combinations as unacceptable. Though no further refinement of either regimen is planned, the authors’ suggestion that the toxicities were related to G-atezo-pola was supported by the less frequent AE rate in the rituximab combination.

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