TY - JOUR
T1 - Comparative Effectiveness of Ciltacabtagene Autoleucel in CARTITUDE-4 Versus Real-World Physician’s Choice of Therapy from the Flatiron Registry in Lenalidomide-Refractory Multiple Myeloma
AU - Touzeau, Cyrille
AU - Lipe, Brea
AU - Khan, Abdullah M.
AU - Dhakal, Binod
AU - Nair, Sandhya
AU - He, Jianming
AU - Mendes, João
AU - Lee, Seina
AU - Lonardi, Carolina
AU - Slaughter, Ana
AU - Lendvai, Nikoletta
AU - Schecter, Jordan M.
AU - Chen, Diana
AU - Zhao, Man
AU - Yeh, Tzu Min
AU - Leleu, Xavier
AU - Puig, Noemí
AU - Dytfeld, Dominik
AU - Zamagni, Elena
AU - Weisel, Katja
AU - Karlin, Lionel
AU - Delforge, Michel
AU - Corradini, Paolo
AU - Mina, Roberto
AU - Roeloffzen, Wilfried
AU - Sidana, Surbhi
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/10
Y1 - 2025/10
N2 - Introduction: Ciltacabtagene autoleucel (cilta-cel) is approved for relapsed or refractory multiple myeloma (RRMM). In the CARTITUDE-4 study (NCT04181827), cilta-cel demonstrated superior efficacy versus pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone in patients with RRMM after 1–3 prior lines of therapy (LOT). We conducted an indirect treatment comparison to understand the comparative efficacy of cilta-cel versus real-world (RW) physician’s choice of treatment for lenalidomide-refractory MM. Methods: De-identified data from the Flatiron Health MM cohort registry (January 2020 to May 2024) were compared with data from CARTITUDE-4 (data cutoff May 1, 2024). Key eligibility criteria for CARTITUDE-4 were used to match patients from the Flatiron database. Baseline covariates of prognostic significance were adjusted using inverse probability of treatment weighting. Outcomes for comparative effectiveness included progression-free survival (PFS), RW PFS, time to next treatment (TTNT), and overall survival (OS). Sensitivity analyses were conducted. Results: The CARTITUDE-4 cohort included data from 208 patients who received cilta-cel; the median follow-up was 33.6 months. The real-world cohort included 932 patients (1445 eligible LOT) from the Flatiron database; the median follow-up was 23.6 months. In base case analyses, compared with the Flatiron cohort, patients treated with cilta-cel had improved PFS (hazard ratio [HR] 0.29 [95% confidence interval (CI)] 0.22–0.36; p < 0.001), RW-PFS (HR 0.29 [95% CI 0.23–0.37]; p < 0.001), TTNT (HR 0.32 [95% CI 0.25–0.41]; p < 0.001), and OS (HR 0.59 [95% CI 0.41–0.84]; p = 0.003). These findings were consistent across all sensitivity analyses. Conclusion: Cilta-cel lengthened TTNT and demonstrated meaningful prolongation in PFS and OS compared with real-world physician’s choice for lenalidomide-refractory MM. These data highlight the value of cilta-cel as an effective therapy in earlier-line patients with relapsed, lenalidomide-refractory MM exposed to proteasome inhibitors and immunomodulatory drugs. Trial registration: CARTITUDE-4: ClinicalTrials.gov ID NCT04181827.
AB - Introduction: Ciltacabtagene autoleucel (cilta-cel) is approved for relapsed or refractory multiple myeloma (RRMM). In the CARTITUDE-4 study (NCT04181827), cilta-cel demonstrated superior efficacy versus pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone in patients with RRMM after 1–3 prior lines of therapy (LOT). We conducted an indirect treatment comparison to understand the comparative efficacy of cilta-cel versus real-world (RW) physician’s choice of treatment for lenalidomide-refractory MM. Methods: De-identified data from the Flatiron Health MM cohort registry (January 2020 to May 2024) were compared with data from CARTITUDE-4 (data cutoff May 1, 2024). Key eligibility criteria for CARTITUDE-4 were used to match patients from the Flatiron database. Baseline covariates of prognostic significance were adjusted using inverse probability of treatment weighting. Outcomes for comparative effectiveness included progression-free survival (PFS), RW PFS, time to next treatment (TTNT), and overall survival (OS). Sensitivity analyses were conducted. Results: The CARTITUDE-4 cohort included data from 208 patients who received cilta-cel; the median follow-up was 33.6 months. The real-world cohort included 932 patients (1445 eligible LOT) from the Flatiron database; the median follow-up was 23.6 months. In base case analyses, compared with the Flatiron cohort, patients treated with cilta-cel had improved PFS (hazard ratio [HR] 0.29 [95% confidence interval (CI)] 0.22–0.36; p < 0.001), RW-PFS (HR 0.29 [95% CI 0.23–0.37]; p < 0.001), TTNT (HR 0.32 [95% CI 0.25–0.41]; p < 0.001), and OS (HR 0.59 [95% CI 0.41–0.84]; p = 0.003). These findings were consistent across all sensitivity analyses. Conclusion: Cilta-cel lengthened TTNT and demonstrated meaningful prolongation in PFS and OS compared with real-world physician’s choice for lenalidomide-refractory MM. These data highlight the value of cilta-cel as an effective therapy in earlier-line patients with relapsed, lenalidomide-refractory MM exposed to proteasome inhibitors and immunomodulatory drugs. Trial registration: CARTITUDE-4: ClinicalTrials.gov ID NCT04181827.
KW - CAR-T
KW - CARTITUDE-4
KW - Ciltacabtagene autoleucel
KW - Flatiron health database
KW - Indirect treatment comparison
KW - Real-world data
KW - Relapsed or refractory multiple myeloma
UR - https://www.scopus.com/pages/publications/105012841831
U2 - 10.1007/s12325-025-03308-2
DO - 10.1007/s12325-025-03308-2
M3 - Article
C2 - 40768190
AN - SCOPUS:105012841831
SN - 0741-238X
VL - 42
SP - 5023
EP - 5041
JO - Advances in therapy
JF - Advances in therapy
IS - 10
ER -