Polatuzumab vedotin, obinutuzumab, and venetcolax has shown promise in the response rates at the end of induction (EOI) in patients with relapsed or refractory (R/R) follicular lymphoma (FL), according to a phase 1b/2 study being presented at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

At the primary analysis as of Oct 5, 2020, 74 patients with R/R FL (median age, 64 years) received polatuzumab vedotin 1.4-1.8mg/kg intravenously (IV) in dose escalation (DE) every 21 days for 6 cycles or the recommended Phase 2 dose (RP2D) on D1; plus obinutuzumab at 1000mg IV (CI: D1, D8, D15; C2-6, D1); and oral venetoclax at 200-800mg (DE or RP2D; D1-21).

Patients with complete response (CR), partial response (PR), or stable response (SD) at EOI received maintenance with obinutuzumab at 1000mg (D1 every 2 months for 24 months), and venetoclax 200-800mg daily for 8 months.

The primary end points were safety/tolerability, and positron emission tomography (PET)-CR rate at EOI by independent review committee (IRC) using modified Lugano criteria.

Overall, 86% of patients had Ann Arbor Stage III-IV; 55% had an FL International Prognostic Index high risk at ≥3; 16% had bulky disease ≥7cm; 74% received 2 or more prior lines of therapy; 51% were refractory to the last prior therapy; 55% were refractory to any prior anti-CD20 therapy; and 55% were double refractory to both anti-CD20 therapy and an alkylating agent.

Adverse events (AEs) of grade 3 to 4 occurred in 73% of patients. The most common AEs include neutropenia (39%), thrombocytopenia (19%), and infections (16%). AEs led to dose reductions in 38% and interrupted 68% of patients. There was 1 fatal AE reported.

In total, 49 patients were treated at RP2D and were evaluated on efficacy. The PET-CR rate at EOI by IRC was 57% (n = 28), and the objective response rate (ORR) was 71% (n=35). The PR was 14% (n = 7), SD was 16% (n = 8), and 4 patients had progressive disease (PD, 8%). At median follow-up of 14.4 months, the 12-month progression-free survival (PFS) was 73%, (95% CI, 59.4-86.9). However, the median PFS was not met.

“The safety profile of polatuzumab-obinutuzumab-venetoclax is consistent with the known profiles of the individual drugs. Response rates at EOI with polatuzumab-obinutuzumab-venetoclax are encouraging in this RR FL patient population. Additional follow-up is needed to assess PFS benefit during maintenance treatment and beyond,” said Rajat Bannerji, MD, PhD, hematologist/oncologist and chief of hematologic malignancies at the Rutgers Cancer Institute of New Jersey, et al.—Emily Bader

Bannerji R, Yuen S, Phillips TJ, et al. Polatuzumab vedotin + obinutuzumab + venetoclax in patients with relapsed/refractory (R/R) follicular lymphoma (FL): Primary analysis of a phase 1b/2 trial. Presented at: the 2021 ASCO Annual Meeting; June 4-8, 2021; virtual. Abstract 7534.