Estimation of Eligibility and Response to Bispecific Antibody Therapy in US Patients with Lymphoma and Multiple Myeloma

Background

Bispecific antibodies (bsAbs) have gained momentum during the last several years in the treatment of hematological malignancies. Their novel mechanism of action has resulted in improvement in outcomes of patients with hematological malignancies refractory and/or relapsing after conventional therapies. This resulted in 7 regulatory approvals of bsAbs by the US FDA to treat hematological malignancies. Excluding blinatumomab, all have gained accelerated approval through phase II trials to treat relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL); primarily diffuse large B-cell lymphoma (DLBCL and follicular lymphoma (FL), and R/R multiple myeloma (MM). Although these agents are associated with overall response rates (ORR) of greater than 50% in heavily treated patients, the real-world eligibility and response to these therapies in the United States is not known.

Methods

We aimed to estimate the number of US patients with NHL and MM who are eligible for and may respond to FDA approved bsAbs for R/R NHL and MM. A person was considered to be eligible for treatment with a bsAb if they had the FDA approved indication and inclusion criteria. We defined response based on the best available response rate for that indication from the FDA drug label. We used the incidence rate of NHL and MM from American Cancer Society's Cancer Facts and Figures during the years each bsAb had an approval. We made assumptions to estimate eligibility by incorporating attrition rates between lines of therapy according to what is published in the literature. For NHL, we assumed 75% of NHL diagnoses are DLBCL, while 20% are FL.

For DLBCL, we assumed that 30% (10% primary refractory and 20% in relapse) of newly diagnosed DLCBL would receive a second-line therapy; of these patients, we assumed that 50% would proceed to receive a bsAb as third-line therapy. For FL, we assumed that 75% of newly diagnosed FL patients are grade 1-3A; of these, 85% will require first-line treatment, and 13% of these patients will eventually relapse to receive a bsAb as third-line therapy. For MM, we assumed that 14% of newly diagnosed MM will eventually be triple class refractory (refractory to a proteasome inhibitor, an immunomodulatory drug, and a monoclonal antibody) patients potentially eligible to receive a bsAb. The calculated number of people eligible was multiplied by the overall response rate (ORR) reported in the trial that led to the bsAb approval for each year a therapy had an approval, using the highest calculated response, to estimate the population who would potentially benefit of these therapies.

Results

Six bsAbs were approved in the US since 2022 to treat NLH and MM: epcoritamab and glofitamab in 2023 to treat R/R DLBCL and other mature B-cell neoplasms, mosunetuzumab in 2022 and epcoritamab in 2024 to treat R/R grade 1-3A FL, and for MM, teclistamab in 2022, and elranatamab and talquetamab in 2023. All of them were authorized via accelerated approval after a phase II trial.

There were 80550 and 80620 new NHL cases in 2023 and 2024, respectively, and 12640, 12590, and 12540 new MM cases in 2022, 2023, and 2024, respectively. Of these, we estimated 21033 DLCBL patients would be potentially eligible to receive bsAbs since 2023, 2733 FL patients potentially eligible to receive bsAbs since 2023, and 5666 MM patients potentially eligible to receive bsAbs since 2022.

The percentage of patients per year that were potentially eligible for bsAbs was 13% for DLCBL, 8.5% for FL, and 15% for MM. Based on best available response rates from registration trials, we estimated that 9.6% and 10.5% newly diagnosed NHL and MM patients, respectively, would potentially benefit from bsAbs.

Conclusions

Even though CR and ORR of bsAbs are high for highly pretreated patients, we found the percentage of newly diagnosed NHL and MM patients who would become potentially eligible and would respond to these therapies to be quite low (approximately only 1 out of 10). Even though these conclusions are driven by best-case scenario assumptions and have a risk of bias, they provide insights of the actual impact and reach of these newer therapies.

Hilal:BeiGene: Consultancy, Research Funding.