Polatuzumab Vedotin Approved in Combination with R-CHP for Treatment-Naïve DLBCL, High-Grade B-Cell Lymphoma

Polatuzumab vedotin is approved in combination with R-CHP

The FDA has approved polatuzumab vedotin-piiq (Polivy), in combination with rituximab (Rituxan), cyclophosphamide, doxorubicin and prednisone (R-CHP) for the treatment of adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), and patients with high-grade B-cell lymphoma (HGBL) with an international prognostic index (IPI) score of 2 or more.¹

The FDA has also converted the accelerated approval of polatuzumab vedotin in addition to bendamustine and rituximab, for patients with relapsed or refractory DLBCL after 2 or more lines of therapy, into a regular approval.

Findings from the phase 3 POLARIX trial (NCT03274492), in which patients were randomly assigned to either polatuzumab vedotin plus R-CHP (pola-R-CHP) or R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine sulfate, and prednisone) supported the regulatory decision. Data showed that the experimental regimen (n = 440) reduced the risk of disease progression, relapse, or death by 27% compared with R-CHOP (n = 439; HR, 0.73; 95% CI; 0.57-0.95; P < .02). Similar rates of grade 3/4 adverse effects (AEs; 57.7% vs 57.5%, respectively) and serious AEs (34.0% vs 30.6%) were reported between the 2 arms. Grade 5 AEs occurred in 3.0% vs 2.3% of patients in the polatuzumab vedotin and R-CHOP arms, respectively. Dose reductions because of AEs (9.2% vs 13.0%).

“It has been nearly 20 years since a new treatment option has become available to [individuals] with newly diagnosed with diffuse large B-cell lymphoma,” Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development, stated in a news release. “Today’s decision from the FDA to approve [polatuzumab vedotin] Polivy in combination with R-CHP in this setting brings a much-needed new treatment option which may improve outcomes and bring other benefits to many patients with this aggressive lymphoma.”

The most common AEs experienced with pola-R-CHP included peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. Lymphopenia and neutropenia were the most common grade 3 or 4 AEs.

POLARIX was a phase 3, randomized, double-blind study set to evaluate the efficacy, safety, and pharmacokinetics of the combination in patients with previously untreated DLBCL. The trial enrolled 879 patientswho were randomly assigned to receive either pola-R-CHP for 6 cycles, followed by 2 cycles of rituximab; or placebo plus R-CHOP for 6 cycles, followed by 2 cycles of rituximab. Progression-free survival, as assessed by the investigator, was the study’s primary outcome.

Polatuzumab vedotin is a CD79b-directed antibody-drug conjugate. It’s recommended dose of polatuzumab vedotin is 1.8 mg/kg as an intravenous infusion over 90 minutes. This treatment is given every 21 days for 6 cycles. It is advised to premedicate patients with an antihistamine and antipyretic beforehand.²

On treatment, patients should be monitored for peripheral neuropathy, infusion-related reactions, myelosuppression, opportunistic infections, progressive multifocal leukoencephalopathy, tumor lysis syndromes, and hepatotoxicity. This may include monitoring their complete blood counts, monitoring for any new or worsening cognitive, or behavioral changes, as well as monitoring liver enzymes and bilirubin. This agent can cause embryo-fetal toxicity.²

Of note, the concomitant use of this treatment with strong CYP3A inhibitors or inducers has the potential to affect the exposure to unconjugated monomethyl auristatin E (MMAE). Similarly, patients with hepatic impairment are at risk of increased exposure to MMAE. These patients will need to be monitored for adverse reactions.²

References

1. FDA approves Roche’s Polivy in combination with R-CHP for people with certain types of previously untreated diffuse large B-cell lymphoma. News release. April 19, 2023. Accessed April 19, 2023. https://www.globenewswire.com/news-release/FDA-approves-Roche-s-Polivy
2. Polivy. Prescribing information. Genentch, Inc; 2020. Accessed April 19, 2023. https://www.gene.com/download/pdf/polivy_prescribing.pdf

Updated April 20, 2023.