Should Transplant Centers Prioritize Further Stem Cell Collection for Future CAR T-Cell Therapy Boosts? an Economic and Clinical Assessment
Authors: Malek Ehsan , Davila Marco , Tirado Hector , Holtan Shernan G. , Betts Brian , Yu Han 
Published: December 2024

CAR T-cell therapy has significantly transformed the treatment landscape for multiple myeloma (MM), providing a one-time, highly effective therapeutic option for patients with relapsed or refractory disease. However, a major challenge associated with this therapy is immune cell-associated hematological toxicity (ICAHT), which increases susceptibility to severe infections, leading to significant morbidity and mortality. Multiple studies have shown that an autologous stem cell boost using remaining stem cells from a previous autologous stem cell transplant for ICAHT is safe and effective in shortening the duration of neutropenia.

Nevertheless, there is a growing concern about the adequacy of stem cell reserves. As the preference for second transplants has waned, many transplant centers have reduced their threshold for stem cell collection, which may limit the availability of stem cell boosts when needed. This practice adjustment raises the critical question of whether it is prudent to collect extra stem cells for future boosts in CAR T-cell therapy to ensure better patient outcomes.

Our study hypothesizes that maintaining a more extensive stem cell collection for potential future boosts in CAR T-cell therapy can provide significant clinical and economic benefits. The central question remains whether the additional collection of stem cells for future boosts in CAR T-cell therapy is a prudent decision, given the evolving landscape of MM treatment and the shift away from second transplants as a favored option.

Methods: The Markov model simulated patient transitions through various health states over an 8-year period with monthly steps. The states included CAR T therapy, prolonged neutropenia (≥ 30 days), infection, recovery, relapse, and death. Two scenarios were compared: with and without the stem cell boost. Transition probabilities for the no-boost scenario were derived from the CARTITUDE-4 study (i.e., no patient received a stem cell boost in the trial). For the boosted scenario, the probability of transitioning from neutropenia to recovery was calculated based on the study by Mohan et al., which reported on 108 patients with ICAHT who received a stem cell boost. The cost of collecting adequate stem cells for each boost as well as hospital admission due to neutropenic fever was adjusted based on 2024 rates.

Results: For both scenarios, the probability of transitioning from CAR T to prolonged neutropenia was 26%. The probability of transitioning from a neutropenic state to recovery was 75% without the boost and 90% with the boost. Patients without the boost had an average of 6.01 life years, while those receiving the boost had 8.08 life years, indicating that the boost substantially improves overall survival. The cost analysis revealed a total cost of $4,544.43 for the no-boost scenario, compared to $14,034.90 for the boost scenario. Sensitivity analysis examined the impact of varying key parameters such as infection and recovery probabilities, as well as associated costs. Adjusting the infection probability from 0.05 to 0.15 significantly impacted the ICER, with higher infection probabilities increasing costs and influencing the cost-effectiveness of the boost scenario. Changes in recovery probability for both the no-boost (0.30, 0.33, 0.36) and boost scenarios (0.85, 0.90, 0.95) demonstrated that higher recovery probabilities led to better outcomes in terms of both costs and life years gained. Variations in the cost per infection and cost per boost also significantly affected the ICER. Increased infection costs made the boost scenario relatively more cost-effective, while higher boost costs reduced its cost-effectiveness. The Incremental Cost-Effectiveness Ratio (ICER) was calculated at $4,588.08 per life year gained, indicating that the stem cell boost provides additional life years at a moderate cost.

Conclusion: The Markov model suggests that providing a stem cell boost to myeloma patients with prolonged neutropenia post-CAR T-cell therapy significantly improves survival outcomes but incurs somewhat higher costs. The sensitivity analysis highlights the importance of managing infection risks and optimizing recovery probabilities to enhance the cost-effectiveness of the intervention. These insights can aid clinicians and policymakers in making informed decisions regarding the implementation of stem cell boosts in this patient population.