Legend Biotech (LEGN) The 66th American Society of Hematology (ASH) Annual Meeting and Exposition 2024 summary

Key clinical insights and data updates

• Cilta-cel demonstrated significant overall survival and progression-free survival benefits in lenalidomide-refractory multiple myeloma patients, with a 45% reduction in risk of death compared to standard of care at nearly 34 months follow-up.

• Median progression-free survival was not reached in the cilta-cel arm, with a 30-month PFS rate of 59.4% versus 25.7% for standard of care.

• MRD negativity rates were substantially higher with cilta-cel, up to fourfold at the deepest measurable level compared to standard regimens.

• Real-world data from over 250 patients showed outcomes and safety consistent with clinical trials, even in populations not eligible for pivotal studies.

• Outpatient administration of cilta-cel is increasing, with up to 48% of treatments now outside the hospital setting.

Evolving safety profile and management

• Rates of severe CRS and ICANS are lower in recent studies (CARTITUDE-4) compared to earlier trials, attributed to better patient selection and improved management.

• Delayed neurotoxicity, including parkinsonism, has decreased to less than 1% in newer studies, with proactive monitoring and early intervention strategies being adopted.

• Use of low-dose steroids and tracking lymphocyte expansion are emerging as effective mitigation strategies for neurotoxicity.

• No new concerning safety signals have emerged with longer follow-up; second primary malignancy rates are similar between cilta-cel and standard of care.

• Real-world experience suggests that with proper protocols, outpatient administration is feasible and safe for selected patients.

Market adoption, access, and future directions

• Cilta-cel use is expanding into earlier lines of therapy, with significant uptake in second to fourth line settings and no current slot limitations for treatment access.

• Bottlenecks now relate more to apheresis capacity than product availability, with centers able to treat 10–12 patients per month.

• Patient selection and education are critical, with efficacy being the main driver for therapy choice among patients.

• Comparative discussions with emerging therapies (e.g., bispecifics, anito-cel) focus on balancing efficacy, safety, and practical considerations like outpatient use.

• Ongoing studies and real-world data will further clarify optimal patient selection, long-term outcomes, and best practices for toxicity management.