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The FDA approved the antibody-drug conjugate (ADC) polatuzumab vedotin (Polivy) plus standard therapy for certain types of untreated diffuse large B-cell lymphoma (DLBCL), according to a from Genentech.

The approval stipulates use of the first-in-class anti-CD79b ADC in combination with rituximab (Rituxan) and chemotherapy for previously untreated DLBCL, not otherwise specified (NOS), or high-grade B-cell lymphoma in those who have an International Prognostic Index of two or greater.

The action follows a favorable recommendation from the Oncologic Drugs Advisory Committee (ODAC), despite FDA staff members' concerns about the drug's efficacy.

Primary support for the approval came from the phase III randomized POLARIX trial, which compared the long-time standard of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine [Oncovin], prednisone) or polatuzumab plus R-CHOP without vincristine (R-CHP) in patients with newly diagnosed DLBCL.

After a median follow-up of 28.2 months, the results showed that patients randomized to the ADC had a statistically significant 27% improvement in the hazard for disease progression or death. The progression-free survival (PFS) rate at 2 years was 76.7% with polatuzumab/R-CHP and 70.2% with R-CHOP.

During the ODAC meeting, FDA staff noted that the addition of polatuzumab to standard therapy did not improve overall survival, but did improve event-free survival (EFS), adding that the difference in PFS was "modest." Ultimately the committee decided that the benefits were sufficient to support a recommendation for approval.

"I believe this gain in progression-free survival is clinically meaningful for patients, and also leads to a reduction in the need for subsequent therapy," said ODAC member Grzegorz Nowakowski, MD, of the Mayo Clinic Comprehensive Cancer Center in Rochester, Minnesota, in explaining his "yes" vote. "And there were no major adverse toxicity signals, which would have been detrimental in this study."

"However, I would consider this regimen to be an option, rather than a standard, in the setting of a lack of overall survival difference from R-CHOP," he added.

Polatuzumab vedotin previously received for relapsed/refractory DLBCL NOS.

The most common side effects with polatuzumab/R-CHP include nerve problems in the arms and legs, nausea, diarrhea, fatigue, constipation, alopecia, and low blood cell counts.

Correction: This story has been updated to reflect the statistically significant improvement in EFS.

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