Jane N. Winter, MD

Christopher R. Flowers, MD, MS

Jane N. Winter, MD, Professor of Medicine at Northwestern University’s Feinberg School of Medicine and the 2022 President of the American Society of Hematology (ASH), and Christopher R. Flowers, MD, MS, Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, Houston, offered their thoughts on the phase III POLARIX trial.¹

Dr. Winter cautioned that the study needs longer follow-up and confirmation before physicians should jump at adding polutuzumab vedotin-piiq to standard first-line treatment of intermediate/high-risk diffuse large B-cell lymphoma. She said that although the complete response rates were not significantly different, it appears the remissions are “deeper and more profound” and potentially “more durable” than with conventional therapy. “Hopefully, this will translate, in time, to substantial differences” in outcomes, including survival, she said, “though it may be a while before that is demonstrated, because of the effectiveness of second-line treatments.”

This is important because this subset of patients has very limited options: “Providing durable, and hopefully curative, options upfront would be important,” she added.

‘Clinically Meaningful’ Findings

Dr. Flowers first noted that for later lines of therapy, many options are emerging to compete with the existing standard of care, which is stem cell transplant—primarily chimeric antigen receptor (CAR) T-cell therapy and anti-CD20 bispecific T-cell engagers. In the front line, polatuzumab vedotin is now poised to challenge the standard of care, producing a 6.5% absolute improvement in progression-free survival at 24 months.

Although there is not yet an overall survival benefit, Dr. Flowers considers the findings clinically meaning, since progression-free survival in first-line therapy has been established in this malignancy as a surrogate for overall survival. “Progression-free survival is a very meaningful endpoint for patients with diffuse large B-cell lymphoma. This benefit gives us the capacity to improve outcomes in the eligible population. I consider the study findings to be not only statistically significant but also clinically meaningful,” he said.

The findings did draw some questions as to the cost-benefit ratio when adding polatuzumab vedotin, which is considered to be an expensive drug. Before passing judgment, Dr. Flowers suggested waiting for a more detailed analysis of the findings. Although the cost of the drug may be considerable, he pointed out that curing patients upfront will spare them— and society—from paying for subsequent therapies, such as transplant and CAR T-cell therapy and a host of other treatments that have not been shown to be curative. “You’re talking about very expensive therapies, with additional toxicity, so that impacts both cost of treatment and quality of life. If we can keep patients from experiencing disease progression, we can avoid them,” he said. 

DISCLOSURE: Dr. Winter has received honoraria and research support from Merck & Co, Inc. Her spouse has served on data and safety monitoring boards for Ariad/Takeda, Epizyme, and Novartis; and has served as a consultant to Novartis, CVS Caremark, Agios, Gilead, Janssen, and Actinium Pharma. Dr. Flowers has served as a consultant to AbbVie, AstraZeneca, Bayer, BeiGene, Celgene/Bristol Myers Squibb (unpaid), Denovo Biopharma, Genentech/Roche (unpaid), Gilead, OptumRx, Karyopharm, Pharmacyclics/Janssen, and Spectrum; and has received research funding from AbbVie, Acerta, BeiGene, Celgene/Bristol Myers Squibb, Gilead, Genentech/Roche, Janssen Pharmaceuticals, Millennium/Takeda, Pharmacyclics, TG Therapeutics, Burroughs Wellcome Fund, Eastern Cooperative Oncology Group, National Cancer Institute, and the V Foundation.

REFERENCE

1. Tilly H, Morschhauser F, Sehn L, et al: The POLARIX Study. 2021 ASH Annual Meeting & Exposition. Abstract 2. Presented December 14, 2021.