In this study, the researchers evaluated the use of standard of care (SOC) ciltacabtagene autoleucel in a patient population and compared it to the outcomes observed in the CARTITUDE-1 clinical trial. They found that a significant percentage of patients (57%) in the study population would have been ineligible for participation in the trial. The most common reasons for ineligibility were cytopenias, oligo or non-story disease, organ dysfunctions, poor ECOG performance status, prior BCMA exposure, and the presence of plasma cell leukemia.
The overall response rate (ORR) in the study population treated with SOC cilta-cel was 89%, with a complete response rate or better of 56%. In comparison, the CARTITUDE-1 trial reported an ORR of 98% and a complete response rate or better of 83%. Despite the higher eligibility criteria and more aggressive disease features in the study population, the response rates were still favorable.
The majority of patients (84%) received lymphodepletion with Fludarabine and Cyclophosphamide, while 16% received alternative lymphodepleting chemotherapy such as Bendamustine, Cyclophosphamide alone, or a combination of Cyclophosphamide with Cladribine.
Cytokine release syndrome (CRS) was observed in about 80% of patients, with 5% experiencing grade 3 or higher CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in approximately 18% of patients, with 6% experiencing grade 3 or higher events. To manage these toxicities, supportive medications such as Tocilizumab, steroids, and Anakinra were used. Tocilizumab was received by 61% of patients, corticosteroids by 41%, and Anakinra by 13%.
Delayed neurotoxicity (NT) occurred in 12% of patients, with specific neurological adverse events including Parkinsonian-like features (1%) and Bells Palsy (6%). Most patients with Bells Palsy (35%) recovered their neurologic function. Steroids were the mainstay of treatment for delayed neurotoxicity.
Dr. Doris Hansen from Moffitt Cancer Center discusses the next step in this SOC Cilta-cel research is to further investigate the impact of prior BCMA exposure and lymphodepletion chemotherapy on outcomes. The researchers are also focusing on identifying features or characteristics that can predict the risk of delayed neurologic toxicity. More patients will be followed to gain a better understanding of these factors.
In conclusion, the use of SOC ciltacabtagene autoleucel demonstrated favorable outcomes in terms of safety and efficacy. Patients who do not meet clinical trial criteria can still benefit from this therapy, and its delivery appears to be safe outside the clinical trial setting. Further research is needed to refine patient selection and management of toxicities.