In a phase Ib/II trial reported in the Journal of Clinical Oncology, Laurie H. Sehn, MD, MPH, and colleagues found that the addition of polatuzumab vedotin to bendamustine/rituximab improved response rate and progression-free and overall survival among transplantation-ineligible patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study—GO29365—supported the June 2019 accelerated approval of polatuzumab vedotin for use in combination with bendamustine/rituximab in adult patients with relapsed or refractory DLBCL after at least two prior therapies.  

Laurie H. Sehn, MD, MPH

Study Details

In the international, multicenter, open-label trial, polatuzumab vedotin was examined in combination with bendamustine/obinutuzumab in 27 patients (6 from phase Ib safety run-in and 21 from phase Ib/II expansion cohort) in a single-arm component, and compared in combination with bendamustine/rituximab (n = 40) vs bendamustine/rituximab alone (n = 40) in a randomly assigned component. Patients received up to six 21-day cycles of treatment. All patients received bendamustine 90 mg/m² on days 2 and 3 of cycle 1 and then days 1 and 2 of subsequent cycles, and either rituximab 375 mg/m² on day 1 of each cycle or obinutuzumab 1,000 mg on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles. Polatuzumab vedotin was given at 1.8 mg/kg on day 2 of cycle 1 and day 1 of subsequent cycles.

The primary endpoint was complete response (CR) at the end of treatment on independent review committee (IRC) assessment using modified Lugano criteria. Patients had received a median of two prior lines of treatment.

Treatment Outcomes

IRC-assessed CR was observed in 8 (29.6%) of 27 patients receiving polatuzumab vedotin plus bendamustine/obinutuzumab. Overall, response was observed in 11 patients (40.7%); median duration of response was 28.4 months. At median follow-up of 27.0 months, median progression-free survival was 6.3 months and median overall survival was 10.8 months.

In the randomized comparison, CR was observed in 16 patients (40.0%) in the polatuzumab vedotin plus bendamustine/rituximab group vs 7 patients (17.5%) in the bendamustine/rituximab alone group (P = .026). Overall, response was observed in 18 patients (45.0%) vs 7 patients (17.5%) and median durations of response were 12.6 months vs 7.7 months. Responses in seven patients in the polatuzumab vedotin plus bendamustine/rituximab group persisted for > 20 months (range = > 20.0 to > 22.5 months), with these patients remaining in CR at last follow-up. After median follow-up of 22.3 months, median progression-free survival was 9.5 vs 3.7 months (hazard ratio [HR] = 0.36, P < .001) and median overall survival was 12.4 vs 4.7 months (HR = 0.42, P = .002).

Adverse Events

Compared with the bendamustine/rituximab group, the polatuzumab vedotin plus bendamustine/rituximab group had higher rates of grade 3 or 4 neutropenia (46.2% vs 33.3%), anemia (28.2% vs 17.9%), and thrombocytopenia (41% vs 23.1%), and similar rates of grade 3 or 4 infection (23.1% vs 20.5%). Rates of red blood cell (25.6% vs 20.5%) and platelet transfusion (15.4% vs 15.4%) were similar in the two groups. The incidence of any-grade peripheral neuropathy was 43.6% vs 7.7%; all events were grade 1 or 2 and resolution was observed in most patients. Adverse events led to death in 9 vs 11 patients, with infection (4 vs 4 patients) being the most common cause.

The investigators concluded, “Polatuzumab vedotin combined with bendamustine/rituximab resulted in a significantly higher CR rate and reduced the risk of death by 58% compared with bendamustine/rituximab [alone] in patients with transplantation-ineligible [relapsed or refractory] DLBCL.”

Dr. Sehn, of BC Cancer Centre for Lymphoid Cancer, Vancouver, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by F. Hoffmann-La Roche and Genentech. For full disclosures of the study authors, visit jco.ascopubs.org.