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

Abstract

The ZUMA-7 study demonstrated that Axicabtagene ciloleucel (axi-cel) improved event-free survival (EFS) compared to standard of care (SOC) salvage chemoimmunotherapy followed by autologous stem cell transplant in primary refractory/early relapsed diffuse large B-cell lymphoma (DLBCL) leading to its recent FDA 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 to 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/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/QALY ($93,547/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 RR-DLBCL is cost-effective when compared to SOC at WTPs of $150,000/QALY. However, its cost-effectiveness is highly dependent on long-term outcomes. Routine usage of second-line CAR-T would add significantly to healthcare expenditures in the USA (>$1 billion each year), even when used in a high-risk subpopulation. Further reductions in the cost of CAR-T are needed to be affordable in many regions of the world.

Cost-effectiveness of Axicabtagene Ciloleucel and Tisagenlecleucel as Second-line or Later Therapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

“…Similarly, Kambhampati and colleagues concluded that second-line axicabtagene ciloleucel is cost-effective, with an ICER of $93 547 per QALY. The study by Perales et al did not account for progression-related costs associated with CAR T cell crossover, while the study by Kambhampati et al modeled these outcomes based on the ZUMA-1 study. Our findings aligned with these results, although the standard parametric modeling approach that we used yields fewer mean survival gains than the mixture cure modeling approach and is considered more conservative …”

“…In 2022, two other reports have been published suggesting that second-line axicabtagene ciloleucel would be cost-effective from US health care sector perspective. 40,41 Perales and colleagues 41 used a mixture of cure models to extrapolate survival outcomes from axicabtagene ciloleucel as reported in ZUMA-7 and concluded that second-line axicabtagene ciloleucel is a costeffective treatment, with an ICER of $66 381 per QALY. Similarly, Kambhampati and colleagues 40 concluded that second-line axicabtagene ciloleucel is cost-effective, with an ICER of $93 547 per QALY.…”

“…40,41 Perales and colleagues 41 used a mixture of cure models to extrapolate survival outcomes from axicabtagene ciloleucel as reported in ZUMA-7 and concluded that second-line axicabtagene ciloleucel is a costeffective treatment, with an ICER of $66 381 per QALY. Similarly, Kambhampati and colleagues 40 concluded that second-line axicabtagene ciloleucel is cost-effective, with an ICER of $93 547 per QALY. The study by Perales et al 41 did not account for progression-related costs associated with CAR T cell crossover, while the study by Kambhampati et al 40 modeled these outcomes based on the ZUMA-1 study.…”

Cost-Effectiveness Analyses in AML: What Have We Learned, How Should This Impact Patient Care, and What Needs to Be Done in the Future?

“…Although recent studies have highlighted that novel therapies with high up-front costs in hematologic malignancies, such as CAR T-cell therapy in B-cell lymphomas, can be cost-effective, it is important to highlight that most of the targeted agents recently approved for AML are not curative. 40 Finally, a key consideration when interpreting costeffectiveness analyses is whether such analyses were funded by the pharmaceutical industry or were conducted independently or by public agencies, such as the National Institute for Health and Care Excellence (NICE) in the United Kingdom. 41,42 In the following case studies, we use recent cost-effectiveness analyses of liposomal cytarabine/daunorubicin (CPX-351) and azacitidine/venetoclax to highlight how different assumptions of effectiveness, costs, and healthcare resource utilization lead to substantially different conclusions (Table 2).…”

“…However, in contrast to other hematologic malignancies, such as multiple myeloma, chronic lymphocytic leukemia, or lymphoma, such studies are not available in AML, which limits (or even precludes) cost-effectiveness analyses seeking to evaluate an optimal therapeutic sequence. 40,65,66 Because the conduct of costeffectiveness analyses in these different scenarios is unlikely due to the absence of clinical trial data informing the model inputs, conclusions regarding the cost-effectiveness of a given treatment strategy should clearly not be overinterpreted and may not apply to other subsets of patients.…”