Polatuzumab vedotin regimen induces complete responses in relapsed/refractory diffuse large B-cell lymphoma
Polatuzumab vedotin combined with bendamustine and rituximab demonstrated encouraging rates of complete response among patients with transplantation-ineligible, relapsed/refractory diffuse large B-cell lymphoma, according to results of a phase 1b/phase 2 trial published in Journal of Clinical Oncology.
The combination also reduced the risk for death by more than half compared with bendamustine and rituximab alone, results showed.
“Patients with relapsed/refractory DLBCL who are transplant ineligible have remarkably poor outcomes with limited treatment options. There is a great need to develop novel agents in this setting to enable prolonged disease control with minimal toxicity,” Laurie H. Sehn, MD, MPH, chair of the lymphoma tumor group at British Columbia Cancer Agency and clinical assistant professor in the division of medical oncology at University of British Columbia, told HemOnc Today. “This randomized phase 2 trial demonstrates that the combination of polatuzumab vedotin with bendamustine and rituximab resulted in improved complete response rates, PFS and OS, compared with bendamustine and rituximab alone. Importantly, a proportion of patients achieved durable control without need for further therapy.”
Sehn and colleagues sought to assess the use of polatuzumab vedotin (Polivy, Genentech), which targets the B-cell receptor component, among this patient population, for which limited treatment options exist.
For phase 1b of the study, researchers assessed the safety of polatuzumab vedotin combined with bendamustine and rituximab in six patients, and polatuzumab vedotin plus bendamustine and obinutuzumab (Gazyva, Genentech) in another six patients.
Phase 2 of the study included an expansion cohort of 21 patients treated with polatuzumab vedotin plus bendamustine and obinutuzumab and a cohort of 80 patients randomly assigned to polatuzumab vedotin combined with bendamustine and rituximab (n = 40; median age, 67 years; 70% men) or bendamustine and rituximab alone (n = 40; median age, 71 years; 62.5% men). Thirty-nine patients per arm received treatment.
Patients received 90 mg/m² IV bendamustine on days 2 and 3 of cycle 1 and days 1 and 2 of subsequent cycles. They also received either 375 mg/m² IV rituximab on day 1 of each cycle or 1,000 mg/m² IV obinutuzumab on days 1, 8 and 15 of cycle 1 and on day 1 of subsequent cycles.
Patients treated with polatuzumab vedotin received 1.8 mg/kg on day 2 of cycle 1 and on day 1 of subsequent cycles. Treatment continued for up to six 21-day cycles.
Independent review committee (IRC)-assessed complete response rate at the end of treatment served as the primary endpoint. Duration of response, PFS and OS served as secondary endpoints.
Median follow-up was 27 months.
Results showed a complete response rate of 29.6% and a median OS of 10.8 months among patients assigned polatuzumab vedotin plus bendamustine and obinutuzumab.
Patients randomly assigned polatuzumab vedotin with bendamustine and rituximab vs. bendamustine and rituximab alone had a significantly higher IRC-assessed complete response rate (40% vs. 17.5%; P = .026) and longer IRC-assessed PFS (median, 9.5 months vs. 3.7 months; HR = 0.36; 95% CI, 0.21-0.63) and OS (median, 12.4 months vs. 4.7 months; HR = 0.42; 95% CI, 0.24-0.75).
Grade 3 or grade 4 adverse events more common among those assigned the polatuzumab vedotin combination vs. bendamustine and rituximab alone included neutropenia (46.2% vs. 33%), anemia (28.2% vs. 17.9%) and thrombocytopenia (41% vs. 23.1%). The groups had similar rates of grade 3 to grade 4 infections (23.1% vs. 20.5%).
“Polatuzumab combined with bendamustine and rituximab represents an effective treatment option, with a tolerable safety profile for this unmet need population,” Sehn told HemOnc Today. “Based on the notable efficacy of polatuzumab vedotin in patients with relapsed/refractory DLBCL, numerous trials are underway exploring additional novel combinations. Also, the POLARIX trial, a phase 3 randomized controlled trial comparing standard R-CHOP vs. polatuzumab vedotin-R-CHP in patients with untreated DLBCL has been completed and results are greatly anticipated.” – by Jennifer Southall
For more information:
Laurie H. Sehn, MD, MPH, can be reached at BC Cancer Centre for Lymphoid Cancer, 600 West 10th Ave., Vancouver, BC, V5Z 4E6 Canada; email: firstname.lastname@example.org.
Disclosures: Sehn reports honoraria from and/or consultant/advisory roles with AbbVie, Acerta Pharma, Amgen, Apobiologix, AstraZeneca, Celgene, F. Hoffmann-La Roche, Genentech, Gilead Sciences, Janssen-Ortho, Karyopharm Therapeutics, Kite Pharma, Lundbeck, Merck, Morphosys, Seattle Genetics, Takeda, Teva and TG Therapeutics; and institutional research funding from F. Hoffmann-La Roche. Please see the study for all authors’ relevant financial disclosures.