TY - JOUR
T1 - Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4)
T2 - results from a randomised, open-label, phase 3 trial
AU - Mina, Roberto
AU - Mylin, Anne K.
AU - Yokoyama, Hisayuki
AU - Magen, Hila
AU - Alsdorf, Winfried
AU - Minnema, Monique C.
AU - Shune, Leyla
AU - Isufi, Iris
AU - Harrison, Simon J.
AU - Shah, Urvi A.
AU - Schecter, Jordan M.
AU - Vogel, Martin
AU - Lendvai, Nikoletta
AU - Gries, Katharine S.
AU - Katz, Eva G.
AU - Slaughter, Ana
AU - Lonardi, Carolina
AU - Gilbert, Jane
AU - Li, Quanlin
AU - Deraedt, William
AU - Filho, Octavio Costa
AU - Patel, Nitin
AU - Florendo, Erika
AU - Karlin, Lionel
AU - Weisel, Katja
N1 - Publisher Copyright:
© 2025 Elsevier Ltd
PY - 2025/1
Y1 - 2025/1
N2 - Background: In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes. Methods: In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 106 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone). Eligible patients had relapsed, lenalidomide-refractory multiple myeloma, received one to three previous treatment lines including a proteasome inhibitor and an immunomodulatory drug, and had an ECOG performance status of 0 or 1. Secondary endpoints reported here include time to sustained worsening of symptoms (Multiple Myeloma Symptom and Impact Questionnaire [MySIm-Q]; a key secondary endpoint) and change in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core C30 (intention-to-treat population) and EuroQol 5-Dimension 5-Level (EQ-5D-5L; intention-to-treat population). This study is registered with ClinicalTrials.gov number NCT04181827 and is ongoing. Findings: Patients were enrolled from July 10, 2020, to Nov 17, 2021, and 419 of 516 screened patients were randomly assigned (cilta-cel, n=208; standard of care, n=211; median follow-up, 15·9 months [IQR 12·4 to 17·8]); median age was 61 years. 191 (92%) of 208 patients in the cilta-cel group and 190 (91%) of 209 evaluable patients in the standard- of-care group completed baseline assessments. MySIm-Q compliance post-baseline was 70 to 81% (cilta-cel) and 79 to 89% (standard of care). MySIm-Q median time to sustained symptom worsening with cilta-cel versus standard of care was 23·7 versus 18·9 months (HR 0·42; 95% CI 0·26 to 0·68). 12-month mean changes for EORTC global health status (GHS) were +10·1 (95% CI 7·0 to 13·1) and –1·5 (95% CI –5·3 to 2·3) points and were +8·0 (95% CI 5·2 to 10·7) and +1·4 (95% CI –1·9 to 4·7) points for EQ-5D-5L visual analogue scale (VAS). Rates of clinically meaningful improvements in GHS and VAS were higher with cilta-cel than with standard of care. Interpretation: Health-related QoL improvements and delayed symptom worsening support cilta-cel's clinical efficacy in lenalidomide-refractory disease. Funding: Janssen Research & Development, Legend Biotech USA.
AB - Background: In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes. Methods: In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 106 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone). Eligible patients had relapsed, lenalidomide-refractory multiple myeloma, received one to three previous treatment lines including a proteasome inhibitor and an immunomodulatory drug, and had an ECOG performance status of 0 or 1. Secondary endpoints reported here include time to sustained worsening of symptoms (Multiple Myeloma Symptom and Impact Questionnaire [MySIm-Q]; a key secondary endpoint) and change in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core C30 (intention-to-treat population) and EuroQol 5-Dimension 5-Level (EQ-5D-5L; intention-to-treat population). This study is registered with ClinicalTrials.gov number NCT04181827 and is ongoing. Findings: Patients were enrolled from July 10, 2020, to Nov 17, 2021, and 419 of 516 screened patients were randomly assigned (cilta-cel, n=208; standard of care, n=211; median follow-up, 15·9 months [IQR 12·4 to 17·8]); median age was 61 years. 191 (92%) of 208 patients in the cilta-cel group and 190 (91%) of 209 evaluable patients in the standard- of-care group completed baseline assessments. MySIm-Q compliance post-baseline was 70 to 81% (cilta-cel) and 79 to 89% (standard of care). MySIm-Q median time to sustained symptom worsening with cilta-cel versus standard of care was 23·7 versus 18·9 months (HR 0·42; 95% CI 0·26 to 0·68). 12-month mean changes for EORTC global health status (GHS) were +10·1 (95% CI 7·0 to 13·1) and –1·5 (95% CI –5·3 to 2·3) points and were +8·0 (95% CI 5·2 to 10·7) and +1·4 (95% CI –1·9 to 4·7) points for EQ-5D-5L visual analogue scale (VAS). Rates of clinically meaningful improvements in GHS and VAS were higher with cilta-cel than with standard of care. Interpretation: Health-related QoL improvements and delayed symptom worsening support cilta-cel's clinical efficacy in lenalidomide-refractory disease. Funding: Janssen Research & Development, Legend Biotech USA.
UR - http://www.scopus.com/inward/record.url?scp=85213856090&partnerID=8YFLogxK
U2 - 10.1016/S2352-3026(24)00320-X
DO - 10.1016/S2352-3026(24)00320-X
M3 - Article
AN - SCOPUS:85213856090
SN - 2451-9960
VL - 12
SP - e45-e56
JO - The Lancet Haematology
JF - The Lancet Haematology
IS - 1
ER -