The FDA granted accelerated approval to polatuzumab vedotin-piiq, a CD79b-directed antibody-drug conjugate, in combination with bendamustine and a rituximab product for adult patients with relapsed or refractory diffuse large B-cell lymphoma.
The US Food and Drug Administration (FDA) announced in a press release their approval of the use of polatuzumab vedotin-piiq (Polivy) in combination with bendamustine and a rituximab product for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have had at least two prior therapies.
The approval was based on the phase Ib/II GO29365 study, an open-label multicenter clinical trial.
“Despite meaningful progress in the treatment of diffuse large B-cell lymphoma, treatment options are very limited when the disease is refractory to or recurrent after multiple regimens,” said Sandra Horning, MD, chief medical officer and head of Global Product Development of Polivy’s developer, Genentech, in a press release. “Today’s approval of this Polivy combination will provide a novel treatment that is both immediately available and very much needed for people with this aggressive disease.”
The trial looked at 80 patients with relapsed or refractory DLCBL who have had at least two prior regimens. Patients randomly received either polatuzumab vedotin-piiq in combination with bendamustine and a rituximab product (P+BR) or BR for six 21-day cycles. Via intravenous infusion, polatuzumab vedotin-piiq 1.8 mg/kg was given on the second day of the first cycle and the first day of subsequent cycles. Bendamustine (90 mg/m2 intravenously) was administered on the second and third days of the first cycle and on the first and second days of subsequent cycles. A rituximab product (375 mg/m2 intravenously) was administered on the first day of each cycle, according to the FDA.
At the end of the therapy, no cancer was detected in 40% (95% CI, 25%–57%) of patients with P+BR, as determined by an independent review committee. The complete response for the BR-alone arm was 18% (95% CI, 7%–33%). Of the 25% of patients who had partial or complete response to P+BR, 16 (64%) had response durations of at least 6 months and 12 (48%) had response durations of at least 12 months.
The most common adverse reactions with P+BR (≥ 20%) were low white blood cell count, low platelet count, anemia, peripheral neuropathy, fatigue, diarrhea, fever, decreased appetite, and pneumonia. Serious adverse reactions occurred mostly from infection in 64% of patients. Cytopenias were the most common reason for treatment discontinuation (18% of all patients).
The recommended dose of polatuzumab vedotin-piiq is 1.8 mg/kg as an intravenous infusion over 90 minutes every 21 days for 6 cycles in combination with bendamustine and a rituximab product.
"The FDA’s recent approval of the use of polatuzumab vedotin-piiq in combination with BR will offer an additional option for patients with relapsed DLBCL," said Julie M. Vose, MD, MBA, editor-in-chief of Cancer Network and professor of internal medicine at the University of Nebraska Medical Center. "The addition of the new agent increased the ORR from 25% with BR alone to 63% with the 3-drug regimen. In addition, the CR rate went from 18% to 40%. This represents a clinically meaningful improvement for this patient population when standard treatment options have failed. The side effects were similar to other antibody-drug conjugates and mild to moderate in most cases. This 3-drug regimen will be used for patients with relapsed DLBCL who are not transplant candidates, or as a bridge to transplant or chimeric antigen receptor (CAR-T) cell therapy."
According to Genentech, this is the first and only randomized clinical trial to show higher response rates over BR in people with relapsed/refractory DLBCL who are ineligible for a hematopoietic stem cell transplant.