The FDA recently granted accelerated approval to polatuzumab vedotin-piiq (Polivy), a CD79b-directed antibody-drug conjugate. The CD79b-directed antibody-drug conjugate monoclonal antibody portion binds to CD79b (B-cell–specific surface protein, a component of the B-cell receptor), and Polivy can then be internalized to deliver MMAE (an antimiotic agent) to bind with microtubules and kill the diving cells by inhibiting cell division, including apoptosis. The drug is indicated in combination with bendamustine and rituximab for adults who have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after at least two prior therapies.

The trial was based on Study GO29365, an open-label, multicenter clinical trial that included 80 patients with relapsed or refractory DLBCL after one prior regimen. Patients were randomized by a 1:1 ratio to receive either Polivy in combination with bendamustine and rituximab (P+BR) or BR for six 21-day cycles. Polivy was given as a 1.8-mg/kg IV infusion on Day 2 of cycle one of subsequent cycles. Bendamustine was given as 90 mg/m2 IV on Days 2 and 3 of cycle one and Day 2 of subsequent cycles. Rituximab was given as 375 mg/m2 IV on Day 1 of each cycle.

Those who were not candidates for autologous hematopoietic stem cell transplantation were eligible patients for study entry. The study excluded patients who had grade 2 or higher peripheral neuropathy, prior allogeneic hematopoietic stem cell transplantation, transformed lymphoma, or active central nervous system lymphoma.

The main outcome was based on a complete response rate 6 to 8 weeks after Day 1 of cycle 6. Efficacy was assessed on complete response rate and response duration, as determined by an independent review committee. The complete response rate was 40% with P + BR and 18% with BR alone. The overall response rate (complete and partial) was 68% with P + BR and 25% with BR. Twenty-five patients achieved partial or complete response with P + BR, 16 patients had response durations of at least 6 months, and 12 patients had response durations of at least 12 months.

The most common adverse reaction (at least 20%) with the P + BR group included neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia. The most serious adverse reaction occurred in 64% of patients, most often from infection. The most common reason for treatment discontinuation was cytopenias (18% of all patients). Warnings and precautions are indicated on the prescribing information for peripheral neuropathy, infusion-related reactions, serious and opportunistic infections, progressive multifocal leukoencephalopathy, myelosuppression, tumor lysis syndrome, hepatotoxicity, and embryo-fetal toxicity.

The recommendation for dosing for Polivy is 1.8 mg/kg IV infused over 90 minutes every 21 days for six cycles in combination with bendamustine and rituximab. Premedication with an antihistamine and antipyretic is recommended. There are also recommendations to prevent opportunistic infections, including Pneumoncystis jiroveci pneumonia and herpes virus. Use in the following populations is not recommended: hepatic impairment, lactation, and pregnancy.

Overall, this study provides information on treatment options for those with relapsed or refractory DLBCL. The trial presented higher complete response rate with P + BR than BR alone, and the FDA granted accelerated approval. Healthcare professionals should report all serious adverse events suspected to be associated with use to the FDA’s MedWatch Reporting System.

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