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Polatuzumab Vedotin Plus Bendamustine/Rituximab for Transplantation-Ineligible Relapsed or Refractory DLBCL


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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

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.

KEY POINTS

  • The addition of polatuzumab vedotin to bendamustine/rituximab improved CR rate and overall survival.
  • Median overall survival was 12.4 vs 4.7 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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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