Study: The Cost-effectiveness of Polivy Depends on Outcomes

The cost-effectiveness of a newer drug combination for the treatment of patients with diffuse large B-cell lymphoma (DLBCL) depends on long-term outcomes, finds a new analysis published in the journal Blood.

Swetha Kambhampati, M.D.

Investigators, led by Swetha Kambhampati, M.D., a fellow in the Department of Hematology and Hematopoietic Cell Transplantation at the City of Hope National Medical Center in Duarte, California, assessed the cost effectiveness of of the pola-R-CHP regimen — Genentech’s Polivy (polatuzumab vedotin-piiq) plus the monoclonal antibody rituximab, the chemotherapy agents cyclophosphamide and doxorubicin, and prednisone — with the standard of care for DLBCL.

DLBCL is a cancer that starts in white blood cells, specifically those that make antibodies to fight infections. It is an aggressive disease, with a five-year survival of 64.6%, according to the National Cancer Institute.

Polivy is a first-in-class antibody-drug that targets CD79b, which is expressed on the surface of malignant B cells, the immune cells impacted in some types of non-Hodgkin’s lymphoma (NHL). The FDA approved Polivy in June 2019 to be used in combination with the chemotherapy drug bendamustine and rituximab (Rituxan and its biosimilars) for adult patients with relapsed or refractory diffuse large B-cell lymphoma. Currently, Polivy is used off label in the pola-R-CHP combination.

The standard of care in this patient population is the R-CHOP regimen, which consists of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. This standard of care is curative in about 60% of patients with newly diagnosed DLBCL.

Previous research has shown that DLBCL patients assigned to take the Polivy-containing regimen fare better than those assigned standard treatment for DLBCL, according to results from the POLARIX reported in the New England Journal of Medicine and earlier at the the American Society of Hematology meetiing in December 2021. More specifcially, the research showed that during a follow-up period of 28.2 months, 76.7% of patient who received the combination containing Polivy survived without progression of DLBCL compared with 70.2% of patients in the group assigned to the standard of care.

Genentech said in a press release that it is working with regulatory authorities to make the Polivy-containing treatment regimen available as soon as possible.

For the cost-effectiveness study published in the journal Blood, Kambhampati and colleagues modeled a hypothetical cohort of U.S. adults with treatment-naïve DLBCL to compare the cost effectiveness of the Polivy-containing regimen with standard of care. Outcome measures were reported in incremental cost-effectiveness ratios, with a willingness-to-pay threshold of $150,000/quality-adjusted life-year.

Assuming a five-year progression-free survival of 69.6% with the Polivy regimen and 62.7% with standard of care, Polivy was cost-effective at the willingness-to-pay threshold. But it was no longer cost-effective if its five-year progression-free survival was 66.1% or lower.

Investigators note their assumptions are based on the POLARIX study of two-year progression-free survival. But if the Polivy regimen only delays relapse and more patients have disease progression between two and five years, the Polivy-containing regimen will no longer be cost-effective.

Kambhampati and colleague calculated that if the Polivy regimen was adopted as frontline therapy for all DLBCL patients in the United States, the use of the regimen could lead to an addition $1.8 billion dollars in healthcare expenditures. Strategies to decrease the cost of pola-R-CHP or identify subpopulations that derive the highest benefit would improve its budget impact, they wrote.

"Though the POLARIX trial was not powered to identify differences between subgroups, an exploratory analysis demonstrated that there were higher response rates with pola-R-CHP in patients older than 60, no bulky disease, IPI score 3-5, and in ABC subtype, subpopulations in which pola-RCHP may be more cost-effective," they noted.

The cost-effectiveness study included only direct healthcare costs. Kambhampati and colleagues observed that the cost of Polivy may vary among payers and in different healthcare settings that could influence its cost effectiveness.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for about 22% of newly diagnosed cases of B-cell non-Hodgkin lymphoma in the United States. More than 18,000 people are diagnosed with DLBCL each year.

Genentech continues to study Polivy in ongoing studies investigating combinations with mosunetuzumab and glofitama, two bispecific antibodies also being developed by Genentech. Both products are designed to target CD20 on the surface of B cells and CD3 on the surface of T cells.

Polivy is also being studied with Venclexta (venetoclax), which is being developed by AbbVie and Genentech, and with Rituxan in combination with gemcitabine and oxaliplatin in the phase 3 POLARGO study.