Real World Outcomes with Idecabtagene Vicleucel (Ide-Cel) CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma
Authors: Sidana Surbhi , Ahmed Nausheen , Akhtar Othman S , Heim Michael , Brazauskas Ruta , Hansen Doris K. , Ferreri Christopher , Freeman Ciara Louise L. , Afrough Aimaz , Anderson Larry D. , Dhakal Binod , Dhanda Devender , Gowda Lohith , Hashmi Hamza , Harrison Melanie , Kitali Amani , Mirza Sayeef , Patel Jinalben , Patwardhan Pallavi , Usmani Saad Z , Patel Krina K. , Ganguly Siddhartha , Pasquini Marcelo 
Published: December 2023

Introduction: Idecabtagene vicleucel (ide-cel) was the first FDA approved BCMA targeted CAR-T cell therapy for the treatment of relapsed/refractory multiple myeloma (RRMM). However, clinical trials are highly selective with stringent eligibility criteria. The objective of this study was to evaluate the safety and efficacy of standard of care ide-cel.
Methods: Patients treated with ide-cel were reported to the CIBMTR registry for long-term follow up of safety and efficacy outcomes. The current analysis includes the first 603 adult patients who received infusion with commercial ide-cel for the treatment of RRMM, with at least one follow-up form reported. Patients treated on investigational clinical trials or who received non-conforming products were excluded. Multivariate analysis was done using Cox regression.
Results: Median follow-up of the 603 patients is 6.6 months, with updated follow up to be presented at the meeting. As shown in Table 1a median age of patients was 65 years, 26% (n=157) were ≥70 years old and 59% (n=354) were male. Black and Hispanic patients comprised 13% (n=77) and 7% (n=42) of the cohort, respectively; 23% (n=137) had Karnofsky performance status &lt;80%, 75% (n=451) had ≥ 1 significant comorbidity and 13% (n=77) had platelets &lt;50,000/µL. Patients for whom data on prior lines of therapy (LoT) were documented (n=470), the median prior LoT was 7 (4-21), 36% (n=217) had penta-refractory disease and 5% (n=28) had received prior-BCMA directed CAR T cell therapy. Data on the use of other BCMA targeting agents are being gathered. 17% (56/331 with PET-CT data) of patients had extramedullary disease (EMD) and 1.5% (n=9) had plasma cell leukemia. High risk cytogenetics [del17p, t(4;14), t(14;16) and/or t(14;20)] were present in 23% (n=141/523) and 45% (n=269/523) when including abnormalities of 1q (ab1q). 36% (n=101/283) of patients had ISS II and 16% (n=46/283) had ISS stage III disease. Lymphodepletion regimen was fludarabine + cyclophosphamide in 95% (n=574) of patients. All patients received ide-cel dose of 300-460 million CAR-T cells, with dose of &gt; 400 million in 56% of patients.
Cytokine release syndrome (CRS) was seen in 81% (n=490) of patients (grade ≥3: 3%), with median time to onset being 2 days. Neurotoxicity was seen in 27% (n=164) of patients (grade ≥3: 4%), with median time to onset being 2 days. Prolonged neutropenia (defined as non-recovery of ANC ≥ 500/uL by day 30) and thrombocytopenia (non-recovery of platelets ≥ 20,000/uL by day 30) was seen in 13% (n=81) and 25% (n=148) of patients, respectively. Hemophagocytic Lymphohistiocytosis-like syndrome was seen in 1% (n=6) and tumor lysis syndrome in 1.5% (n=9) of patients. Clinically significant infections were seen in 42% (n=252) of patients (bacterial: 22%, viral: 23%, fungal: 2%). Second malignancies were seen in 4.5% (n=27) of patients, including AML/MDS in 5 patients. Table 1b shows multivariate analysis for CRS and neurotoxicity. Risk factors associated with higher likelihood of grade &gt;2 CRS were age ≥ 70, female sex and baseline platelets &lt; 50,000/uL. Similarly, higher risk of neurotoxicity was seen with older age, high-risk cytogenetics, lower performance status and platelets &lt; 50,000/uL.
Overall response rate was 71% (n=421), ≥ very good partial response rate was 53% (n=319) and ≥ complete response (CR) rate was 27% (n=162). On multivariate analysis for response, presence of EMD, CAR-T cell dose ≤ 400 million, penta-refractory disease and lower performance status were associated with lower likelihood of CR. Estimated progression free survival (PFS) at 6 months was 62% (95% CI: 58-66%) and overall survival (OS) at 6 months was 82% (95% CI, 79-85%). At last follow-up, 26% of patients have died, majority due to disease progression (70%, n=108); causes of death in the remaining 47 patients were infection (n=15), CRS (n=1), neurotoxicity (n=2), tumor lysis (n=1), organ failure (n=7), second cancer (n=5), intracranial hemorrhage (n=3) and other (n=13).
Conclusion: This is the largest real-world study of ide-cel CAR-T cell therapy in patients with RRMM. We observed a favorable safety and efficacy profile in this real-world population, despite a very heavily pre-treated population and large proportion of patients having co-morbidities that would have made them ineligible for the KarMMa clinical trial. These results further support ide-cel as a therapeutic option for a broad, real-world population of patients with RRMM.