Triplet Combination Safe, Clinically Active in Richter Transformation

The combination of atezolizumab, venetoclax, and obinutuzumab is a safe and active treatment regimen for patients with the diffuse large B-cell lymphoma (DLBCL) variant of Richter transformation, according to data from the MOLTO study.

This multicenter, single-arm, phase II trial was led by Alessandra Tedeschi, MD, of the Niguarda Cancer Center in Milan, Italy, and published in The Lancet Oncology. The researchers aimed “to explore a chemotherapy-free treatment combination that triggers [antitumor] immune responses.”

The study comprised 28 patients from 15 hospitals in Italy and Switzerland who had a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma with transformation to DLBCL.

Patients received 35 cycles of 21 days of intravenous obinutuzumab (100 mg on day 1, 900 mg on day 2, 1,000 mg on day 8, and day 15 of cycle 1; and 1,000 mg on day 1 of cycles 2-8); intravenous atezolizumab (1,200 mg on day 2 of cycle 1 and 1,200 mg on day 1 of cycles 2-18); and continuous oral venetoclax (ramp up from 20 mg per day on day 15 of cycle 1, then 400 mg per day from day 1 of cycle 3 to day 21 of cycle 35).

The primary endpoint was overall response rate (ORR) at day 21 of cycle six, and the median follow-up was 16.8 months. The researchers considered an ORR of 67% or greater to be clinically active.

The ORR was 67.9% (95% CI, 47.6-84.1), with 19 of 28 patients showing a response at cycle six. Sixty-one percent of patients (95% CI, 40.6-78.5) experienced grade 3 or higher treatment-emergent adverse events (TEAE). Neutropenia was the most common TEAE, occurring in 39% of patients. Serious TEAS occurred in 29% of patients, most commonly infections (18%). Two deaths were attributed to AEs but were not considered directly treatment related. Tumour lysis syndrome was not reported.

“The atezolizumab, venetoclax, and obinutuzumab triplet combination was shown to be active and safe, suggesting that this chemotherapy-free regimen could become a new first-line treatment approach in patients with DLBCL [with Richter Transformation],” the researchers concluded.

Reference

Tedeschi A, Frustaci AM, Condoluci A, et al. Atezolizumab, venetoclax, and obinutuzumab combination in Richter transformation diffuse large B-cell lymphoma (MOLTO): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2024;25(10):1298-1309. doi:10.1016/S1470-2045(24)00396-6