Cilta-Cel Yields QOL Benefits and Prolonged Treatment-Free Intervals vs SOC in R/R Myeloma

A single infusion of ciltacabtagene autoleucel (cilta-cel; Carvykti) delayed worsening of disease-related symptoms and functional effects in patients with lenalidomide (Revlimid)–refractory multiple myeloma, who also experienced improved quality of life (QOL) over time compared with those who received standard of care (SOC), according to long-term findings from the phase 3 CARTITUDE-4 trial (NCT04181827).¹

The findings, which were presented at the 50th Annual Oncology Nursing Society Congress, showed that at a median follow-up of 34 months, patients who received cilta-cel had a significantly longer time to worsening (TTW) of symptoms and impacts per the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) assessment compared with those who received SOC. The median TTW of symptoms was not reached (NR; 95% CI, not evaluable [NE]) among patients who received cilta-cel vs 34.3 months (95% CI, 32.2-NE) among those who received SOC (HR, 0.38; 95% CI, 0.24-0.61; P < .0001). Additionally, the median TTW of impacts in these respective arms were 39.2 months (95% CI, 38.7-NE) and 35.9 months (95% CI, 32.2-NE; HR, 0.42 [95% CI, 0.26-0.70; P = .0007). By 30 months following random assignment, 77% of those in the cilta-cel arm had not experienced worsening of symptoms, and 83% had not experienced functional impacts. These respective rates were lower in the SOC arm, at 63% and 69%.

Moreover, a numerically higher proportion of patients in the cilta-cel arm vs the SOC arm achieved clinically meaningful improvements on the MySIm-Q total symptom (cilta-cel, 46.7%; SOC, 37.1%) and impact (42.7%; 31.4%) subscales at month 30. Additionally, patients who received cilta-cel had greater improvements from baseline regarding MySIm-Q symptom and impact scores vs those who received SOC.

At month 30, a numerically higher proportion of patients who received cilta-cel also had clinically meaningful improvements in QOL scores per the European Organization for Research and Treatment of Cancer QOL Questionnaire Core 30 (EORTC QLQ-C30) compared with those who received SOC in the categories of global health status (GHS; cilta-cel, 34.2%; SOC, 30.6%), physical functioning (29.3%; 22.2%), fatigue (53.3%; 44.4%), and pain (44.7%; 36.1%). Additionally, improvements in the least squares mean change from baseline were greater in the cilta-cel arm vs the SOC arm at month 30 in the categories of GHS, physical functioning, fatigue, and pain. Improvements in emotional, cognitive, role, and social functioning, as well as nausea and vomiting symptoms, were also greater with cilta-cel vs SOC.

“Cilta-cel substantially improves health-related QOL and provides prolonged treatment-free intervals, complementing the previously shared progression-free survival [PFS] and overall survival [OS] benefit compared with SOC; these findings support the use of cilta-cel as standard therapy for lenalidomide-refractory patients as early as first relapse,” lead study author Linh Tran, BSN, RN, OCN, and coauthors wrote in a poster of the data. Tran is a clinical trials nurse at Memorial Sloan Kettering Cancer Center in New York, New York.

Looking Back at Efficacy Outcomes From CARTITUDE-4

The global CARTITUDE-4 trial randomly assigned 419 patients to receive either cilta-cel (n = 208) or SOC (n = 211), which included physician’s choice of pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone; or daratumumab (Darzalex), pomalidomide, and dexamethasone. PFS served as the primary end point. Key secondary end points included efficacy, safety, TTW of symptoms in the MySIm-Q total symptom score, and patient-reported outcome (PRO) score changes from baseline.

Cilta-cel was FDA approved in April 2024 for the treatment of patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy—including a proteasome inhibitor and an immunomodulatory drug—and who are refractory to lenalidomide.² This regulatory decision was supported by data from CARTITUDE-4, in which, at a median follow-up of 15.9 months (range, 25-127), treatment with cilta-cel led to a median PFS that was NR vs 11.8 months (95% CI, 9.7-13.8) with SOC in patients who had received 1 to 3 prior lines of therapy (HR, 0.26; 95% CI, 0.18-0.38; P < .001).³ Findings from a longer-term analysis showed that at a median follow-up of 33.6 months, cilta-cel also significantly improved OS vs SOC, with a 30-month OS rate of 76.4% vs 63.8%, respectively (HR, 0.55; 95% CI, 0.39-0.79; P = .0009).⁴

Zooming in on QOL Assessments

PRO assessments used in the present analysis of CARTITUDE-4 included the MySIm-Q and the EORTC QLQ-C30.¹ The MySIm-Q is a multiple myeloma–specific questionnaire that assesses 17 single items across 8 primary domains and 2 secondary domains using a 5-point numeric rating scale. The symptom subscale evaluates neuropathy, pain, fatigue, cognitive symptom, and digestive domains. The impact subscale assesses the effects of treatment on social, emotional, and activity domains.

The EORTC QLQ-C30 is a cancer-specific questionnaire with scores ranging from 0 to 100 and includes the GHS scale. Symptom scales measured in this questionnaire include pain, nausea and vomiting, and fatigue. The functional scales include emotional, physical, cognitive, role, and social. Single items also measured in this questionnaire include diarrhea, constipation, appetite loss, dyspnea, insomnia, and financial difficulties.

Diving Into Additional Long-Term QOL and Efficacy Data

As of May 2024, at a median follow-up of 33.6 months (range, 0.1-45.0), the compliance rates for the MySIm-Q and EORTC QLQ-C30 were both generally high. The 30-month compliance rates for these respective assessments were 67% and 68% in the cilta-cel arm, and 83% and 83% in the SOC arm. The main reasons for noncompliance were technical failure and other reasons, including forgetting, mistakes, site error/oversight, site staff not available, used paper, tablet issues, administrative failure, and unknown.

In the cilta-cel and SOC arms, 86% and 77% of patients, respectively, were censored from the MySIm-Q time-to-sustained-worsening analysis. The primary reasons for censorship were progressive disease or receipt of subsequent anti-myeloma therapy (cilta-cel, 32%; SOC, 64%) and study cutoff (57%; 22%).

The median time to next treatment was NR (95% CI, 38.4 months-NE) in the cilta-cel arm vs 13.4 months (95% CI, 12.0-17.1) in the SOC arm (HR, 0.34; 95% CI, 0.26-0.46; P < .0001). Additionally, the median treatment-free survival was NR (95% CI, 36.6 months-NE) for patients who received cilta-cel vs 1.0 months (95% CI, 0.8-1.2) for those who received SOC.

References

1. Tran L, Davis A, Florendo E, Gries K, Bar N. Long-term effects of ciltacabtagene autoleucel on patient-reported outcomes and time to next anti-myeloma therapy versus standard of care in the CARTITUDE-4 trial of patients with lenalidomide-refractory multiple myeloma. Presented at: 50th Annual Oncology Nursing Society Congress; April 9-13, 2025; Denver, Colorado. Abstract I34.
2. Carvykti is the first and only BCMA-targeted treatment approved by the US FDA for patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. News release. Johnson & Johnson. April 5, 2024. Accessed April 12, 2025. https://www.jnj.com/media-center/press-releases/carvykti-is-the-first-and-only-bcma-targeted-treatment-approved-by-the-u-s-fda-for-patients-with-relapsed-or-refractory-multiple-myeloma-who-have-received-at-least-one-prior-line-of-therapy
3. San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347. doi:10.1056/NEJMoa2303379
4. Mateos MV, San-Miguel J, Dhakal B, et al. Overall survival (OS) with ciltacabtagene autoleucel (cilta-cel) versus standard of care (SOC) in lenalidomide (len)-refractory multiple myeloma (MM): phase 3 CARTITUDE-4 study update. Presented at: 2024 International Myeloma Society Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil. Abstract OA-65.