Cilta-cel Boosts Survival in Lenalidomide-Refractory Multiple Myeloma

Treatment with ciltacabtagene autoleucel (cilta-cel; Carvykti) significantly improved overall survival (OS) and patient-reported outcomes vs standard-of-care (SOC) therapy among those with lenalidomide (Revlimid)-refractory multiple myeloma, according to updated findings from the phase 3 CARTITUDE-4 trial (NCT04181827) published in The Lancet Oncology.¹

Data showed that the median OS was not reached (NR; 95% CI, not evaluable [NE]-NE) in the cilta-cel arm vs NR (95% CI, 37.7-NR) in the SOC arm (HR, 0.55; 95% CI, 0.39-0.79; P = .0009). The estimated 30-month OS rates were 76.4% (95% CI, 70.0%-81.6%) vs 63.8% (95% CI, 56.9%-69.9%) in each respective arm. The OS benefits with cilta-cel were typically comparable across prespecified patient subgroups based on disease and demographic characteristics.

Cilta-cel produced a median progression-free survival (PFS) that was NR (95% CI, 34.5-NE) vs 11.8 months (95% CI, 9.7-14.0) with SOC treatment (HR, 0.29; 95% CI, 0.22-0.39). Additionally, the estimated 30-month PFS rates were 59.4% (95% CI, 52.3%-65.7%) and 25.7% (95% CI, 19.8%-31.9%). The PFS benefits among patients who received cilta-cel typically extended across prespecified subgroups.

Measurable residual disease (MRD) negativity at a threshold of 10^–5 and 10^–6, respectively, occurred in 62% and 57% of evaluable patients in the cilta-cel arm compared with 18% and 9% of those in the SOC arm. Additionally, 77% and 24% of patients in each arm experienced a complete response (CR), and 85% vs 67% from each arm had any treatment response.

Based on Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) assessments, the median time to symptom worsening was NR (95% CI, NE-NE) among patients who received cilta-cel vs 34.3 months (95% CI, 32.2-NE) among those who received SOC treatment (HR, 0.38; 95% CI, 0.24-0.61; P <.0001). Data also showed estimated 30-month MySIm-Q event-free rates of 76.8% (95% CI, 67.6%-83.8%) and 63.1% (95% CI, 52.7%-71.8%) in each arm.

“Cilta-cel led to deep and durable disease control in a greater proportion of patients than [SOC], as evidenced by higher rates of sustained MRD negativity in the cilta-cel group,” lead study author Hermann Einsele, MD, a professor from Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Würzburg, Germany, wrote with coauthors in the publication.¹ “In conclusion, a one-time infusion of cilta-cel in CARTITUDE-4 showed significant survival and quality-of-life benefits. These data show that cilta-cel can improve clinical outcomes for patients with lenalidomide-refractory multiple myeloma as early as first relapse.”

In the open-label, multi-center phase 3 CARTITUDE-4 trial, patients were randomly assigned to receive a single infusion of cilta-cel at a target dose of 0.75 x 10⁶ CAR-positive viable T cells/kg 5 to 7 days after lymphodepletion (n = 208) or SOC therapy (n = 211). Those in the SOC arm received pomalidomide (Pomalyst) plus bortezomib (Velcade) and dexamethasone or daratumumab (Darzalex) plus pomalidomide and dexamethasone. All patients in the cilta-cel arm received 1 cycle of bridging therapy with the pomalidomide- or daratumumab-based combination prior to lymphodepletion and infusion.

The trial’s primary end point was PFS. Secondary end points included the CR rate, overall MRD negativity rate, sustained MRD negativity rate, OS, PFS on next-line therapy, time to worsening of symptoms, overall response rate, and safety.

Patients 18 years and older with 1 to 3 prior lines of therapy—including a proteasome inhibitor and an immunomodulatory drug—for multiple myeloma and documented evidence of progressive disease on or within 6 months of the most recent regimen were eligible for enrollment on the trial.² Being refractory to lenalidomide per International Myeloma Working Group consensus guidelines was another requirement for study entry.

Investigators noted that baseline characteristics were comparable between the cilta-cel and SOC therapy arms. The median cilta-cel dose was 0.71 x 10⁶ cells/kg (IQR, 0.62-0.78), and patients in the SOC arm received a median of 12 treatment cycles (IQR, 5-31).

The median PFS on next-line therapy was NR (95% CI, NE-NE) in the cilta-cel arm vs 25.3 months (95% CI, 21.6-32.9) in the SOC arm (HR, 0.46; 95% CI, 0.34-0.63). Post hoc analyses showed that the median treatment-free survival was NR (95% CI, 36.6-NR) in the cilta-cel arm, with an estimated 30-month treatment-free survival rate of 66.0% (95% CI, 58.6%-72.4%).

Maximum grade 3/4 treatment-emergent adverse effects (TEAEs) occurred in 89% of the cilta-cel arm and 93% of those in the SOC arm; the most common grade 3 toxicities included anemia in the cilta-cel group (35%) as well as neutropenia in the SOC population (28%). Serious treatment-related AEs (TRAEs) were noted in 32% and 26% of each respective treatment group. Across the cilta-cel and SOC safety populations, 24% and 39% of patients in each group died due to any cause, including disease progression in 10% vs 25%, respectively.

References

1. Einsele H, San-Miguel J, Dhakal B, et al. Cilta-cel in lenalidomide-refractory multiple myeloma (CARTITUDE-4): an updated analysis including overall survival from an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. Published online January 7, 2026. doi:10.1016/S1470-2045(25)00653-9
2. A study comparing JNJ-68284528, a CAR-T therapy directed against B-cell maturation antigen (BCMA), versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in participants with relapsed and lenalidomide-refractory multiple myeloma (CARTITUDE-4). ClinicalTrials.gov. Updated December 23, 2025. Accessed January 15, 2026. https://tinyurl.com/mw75a2j8