Cost-effectiveness of second-line axicabtagene ciloleucel in relapsed refractory diffuse large B-cell lymphoma

• Published in: Blood Vol. 140; no. 19; pp. 2024 - 2036
• Main Authors: Thiruvengadam, Swetha Kambhampati, Saumoy, Monica, Schneider, Yecheskel, Serrao, Steve, Solaimani, Pejman, Budde, Lihua Elizabeth, Mei, Matthew G., Popplewell, Leslie L., Siddiqi, Tanya, Zain, Jasmine, Forman, Stephen J., Kwak, Larry W., Rosen, Steven T., Danilov, Alexey V., Herrera, Alex F., Thiruvengadam, Nikhil R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.11.2022
• Subjects: Adult; Aged; Antigens, CD19 - therapeutic use; Cost-Benefit Analysis; Humans; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse - pathology; Receptors, Chimeric Antigen; United States; United States
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2022016747

•Second-line axi-cel is provisionally cost-effective in selected primary refractory/early relapsed DLBCL patients at a WTP of $100 000 per QALY.•The cost-effectiveness of second-line axi-cel depends on its long-term outcomes (a 5-year EFS of at least 26.4% is needed). [Display omitted] The ZUMA-7 (Efficacy of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma) study showed that axicabtagene ciloleucel (axi-cel) improved event-free survival (EFS) compared with standard of care (SOC) salvage chemoimmunotherapy followed by autologous stem cell transplant in primary refractory/early relapsed diffuse large B-cell lymphoma (DLBCL); this led to its recent US Food and Drug Administration approval in this setting. We modeled a hypothetical cohort of US adults (mean age, 65 years) with primary refractory/early relapsed DLBCL by developing a Markov model (lifetime horizon) to model the cost-effectiveness of second-line axi-cel compared with SOC using a range of plausible long-term outcomes. EFS and OS were estimated from ZUMA-7. Outcome measures were reported in incremental cost-effectiveness ratios, with a willingness-to-pay (WTP) threshold of $150 000 per quality-adjusted life-year (QALY). Assuming a 5-year EFS of 35% with second-line axi-cel and 10% with SOC, axi-cel was cost-effective at a WTP of $150 000 per QALY ($93 547 per QALY). axi-cel was no longer cost-effective if its 5-year EFS was ≤26.4% or if it cost more than $972 061 at a WTP of $150 000. Second-line axi-cel was the cost-effective strategy in 73% of the 10 000 Monte Carlo iterations at a WTP of $150 000. If the absolute benefit in EFS is maintained over time, second-line axi-cel for aggressive relapsed/refractory DLBCL is cost-effective compared with SOC at a WTP of $150 000 per QALY. However, its cost-effectiveness is highly dependent on long-term outcomes. Routine use of second-line chimeric antigen receptor T-cell therapy would add significantly to health care expenditures in the United States (more than $1 billion each year), even when used in a high-risk subpopulation. Further reductions in the cost of chimeric antigen receptor T-cell therapy are needed to be affordable in many regions of the world. The FDA approved axicabtagene ciloleucel (axi-cel) for second-line treatment of diffuse large B-cell lymphoma (DLBCL) based on the ZUMA-7 study demonstrating that axi-cel improved event-free survival compared to salvage chemotherapy and autologous transplantation. In modeling using a willingness-to-pay threshold of $150 000/quality-adjusted life year, Kambhampati and colleagues demonstrate axi-cel to be cost-effective in about 73% of iterations; however, cost-effectiveness is dependent on favorable long-term outcomes transpiring, and routine use would add >$1 billion to US healthcare expenditures. Further cost reductions are needed to make the therapy widely affordable.