Financial Toxicity of FDA-Approved Hematologic Malignancy Drugs: An Epidemiological Analysis of Cost

Introduction:

Hematologic malignancies (HM) affect over 1.5 million people in the US, with more than 188,000 new cases projected for 2024. Despite the clinical benefits of newly FDA-approved drugs (FDADs), their high costs contribute to financial toxicity (FT), adversely impacting patient access, adherence, and quality of life. This study investigates new FDAD drug costs, the factors influencing these costs, and the position of cellular therapy, such as chimeric antigen receptor T-cell (CAR-T) therapy, in this landscape.

Methods:

We conducted a retrospective review of clinical trials from October 2011 to October 2021, leading to FDA approvals for HM drugs. Drug pricing was determined using the lowest average wholesale price reported by Drugs.com or UpToDate for cash-paying customers. We calculated total cost (TC), mean one-month supply price (OMSP), and cost per month of median progression-free survival (CPFS). TC was based on the total drug amount for an average person (80 kg or 1.7 m² BSA) following the indicated treatment protocol (n = 11) or median duration (n = 24). For drugs without a reported duration (n = 18), median progression-free survival (PFS) was used. TC of CAR-T therapies (n = 7) was considered as the cost of one dose. OMSP was the TC per month of treatment, and for CAR-T therapies, it was the TC per month of PFS. CPFS was TC per month of PFS for therapies with available data (n = 41). Data were sourced from FDA databases, ClinicalTrials.gov, and primary literature. Statistical analyses included t-tests, ANCOVA, and multiple linear regression.

Results:

From 2011 to 2021, 53 drugs, the majority of which were for leukemia (n=23) and lymphoma (n=16), and 7 cellular therapies were approved for HM treatment by the FDA. Per the US Census Bureau, the median American monthly income was $6,361 in 2021, and the median OMSP and CPFS of the new FDADs were $16,277 and $15,758, resulting in an income-to-cost gap of $9,916 and $9,397, respectively. We found that increasing time since FDAD approval was not associated with significantly lower prices; linear regression estimated an annual increase in TC of $5,845 (R-squared .0026, p = 0.698). Drugs approved for use in combination with other therapies showed reduced TC (p = 0.0382) but not OMSP (p = 0.190) or CPFS (p = 0.078) compared to those approved for monotherapy. As expected, the length of therapy was a significant predictor of TC, with each additional month of treatment associated with a $12,831 (p < 0.0001) increase in TC. However, no significant differences in TC (p = 0.911), OMSP (p =.330), or CPFS (p = 0.211) were found between oral (PO), IV, and subcutaneous (SQ) drugs while controlling for length of treatment. CAR-T therapies had significantly higher costs, with a mean TC of $459,865 and an estimated $183,620 (p = 0.0162) higher TC than PO FDADs. None of the new CAR-T cell therapies have first-line indications, but 23 of the new FDADs had first-line indications. However, the line of therapy had no significant effect on TC (p = 0.299), OMSP (p = 0.666), or CPFS (p = 0.370). Also, CAR-T cell therapy did not have a significantly higher TC than FDADs indicated for CML (p = 0.237) or CLL (p = 0.217), and this finding remained insignificant after controlling for the length of treatment.

Conclusion:

FT remains a critical issue for HM patients, intensified by the high costs of new drugs. While PO, IV, and SQ drugs had comparable costs, CAR-T therapies stood out with significantly higher costs, limiting their accessibility. The high costs and significant gap in income-to-cost emphasize the need to focus on the value each drug provides and the need to expand access to potentially valuable but costly drugs for those with limited means.

Kota:Pfizer: Honoraria; Novartis: Honoraria; Kite Pharma: Honoraria. Cortes:Sun Pharma: Consultancy, Research Funding; Syndax: Consultancy; Nerviano: Consultancy; Lilly: Consultancy; Biopath Holdings: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Ascentage: Research Funding; Rigel: Consultancy; AbbVie: Research Funding; Pfizer: Consultancy; Novartis: Consultancy, Research Funding.