The Incremental Benefit Provided by Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Multiple Myeloma (MM) and Diffuse Large B-Cell Lymphoma (DLBCL) When Compared to Real-World Clinical Practice (RWCP)

OBJECTIVES: Review unmet need in the relapsed/refractory (RR) setting in myeloma and B-cell lymphoma and assess incremental benefit provided by CAR-Ts versus RWCP (ciltacabtagene autoleucel/CARVYKTI in MM; axicabtagene ciloleucel/YESCARTA and tisagenlecleucel/KYMRIAH in DLBCL).

METHODS: A targeted literature review was conducted (01/2014-06/2022) and safety, efficacy and health economic data compared for each product versus RWCP in the relevant disease areas; analyses were conducted using the treated patient cohort from each respective CAR-T trial.

RESULTS: Despite advances in treatment, MM remains an incurable haematological cancer. EU 5-year survival rates for MM patients are just 39.6%. There is no well-established standard of care (SOC) for heavily pre-treated MM, with most patients experiencing multiple relapses. EU 5-year survival rates for DLBCL patients are somewhat better than MM at 55.4%. While approximately 65% of newly diagnosed DLBCL patients are cured with existing first-line treatment, ~35% of patients relapse, and options for transplant-ineligible patients remain limited. CAR-Ts have greatly improved complete response (CR) rates in RR patients, with 82.1% more patients achieving ≥CR with CARVYKTI vs. RWCP (82.5% vs. 0.4%) in triple-class exposed RRMM; 42% more patients (54% vs. 12%) with YESCARTA vs. RWCP and 33% more patients (40% vs. 7%) with KYMRIAH vs. RWCP in RR-DLBCL. CAR-Ts also provide significant overall survival (OS) benefits; CARVYKTI reduces risk of death by 80% vs. RWCP in RRMM, with the equivalent reduction for YESCARTA (73%) and KYMRIAH (34%) vs. RWCP in RR-DLBCL.

CONCLUSIONS: CAR-Ts provide significant benefits for patients who are RR to conventional treatments in MM and DLBCL. These patients have fewer available options and for many, CAR-T therapy will provide durable disease remission and be lifesaving. In MM increased probability of CR and improved OS with CARVYKTI vs RWCP can now be provided to a patient population with a very high disease burden.