Cilta-cel in earlier lines improves outcomes over SoC in LEN-refractory MM patients


For patients with heavily pretreated lenalidomide (LEN)-refractory multiple myeloma (MM) who have received ≥3 lines of therapy (LoT), the efficacy of ciltacabtagene autoleucel (cilta-cel) has been demonstrated in previous studies.1 Cilta-cel is a dual-binding, B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor T-cell (CAR-T) therapy, which has achieved a median progression-free survival (PFS) of around 3 years.1

A phase 3 CARTITUDE-4 study was conducted to evaluate the clinical benefits of cilta-cel in the LEN-refractory MM population with earlier LoT (i.e., 1-3 LoT).1 A total of 419 eligible patients were randomized 1:1 to receive either the cilta-cel arm (n=208) or the standard of care (SoC) therapy (n=211).1 The SoC was either the daratumumab + pomalidomide + dexamethasone (DPd) regimen or the pomalidomide + bortezomib + dexamethasone (PVd) regimen, while the cilta-cel arm received 1 cilta-cel infusion at a target of 0.75x106 CAR-T cells/kg.1 The primary efficacy endpoint was PFS.1 The secondary endpoints included overall response rate (ORR), complete response (CR) or more, minimal residual disease (MRD) negativity, overall survival (OS), and safety.1

The results demonstrated that cilta-cel achieved significant PFS benefits in the overall population with a 12-month PFS rate of 76% vs. 49% in the SoC arm and a relative risk reduction of 74% (HR=0.26; 95% CI: 0.18-0.38; p<0.0001).1 The PFS benefit was consistent across different subgroups.1 The cilta-cel arm also obtained a significantly higher ORR of 84.6% vs. 67.3% with SoC (OR=3.0; 95% CI: 1.8-5.0; p<0.0001).1 In addition, significantly more patients who received cilta-cel achieved the duration of response for 12 months (84.7% vs. 63.0%).1 Cilta-cel also improved the rates of overall MRD-negativity at 10-5 vs. SoC (60.6% vs. 15.6%; OR=8.7; p<0.0001).1


Primary endpoints:

  • The primary efficacy endpoint was PFS1
  • The 12-month PFS rates were 76% with cilta-cel and 49% with SoC, demonstrating a 74% risk reduction in disease progression (HR=0.26; 95% CI: 0.18-0.38; p<0.0001) in the intention-to-treat (ITT) population1
  • PFS benefits were seen across different patient subgroups, including those with ≥2 high-risk cytogenetics, soft-tissue plasmacytomas, International Staging System (ISS) stage III, and prior exposure to anti-cluster of differentiate (CD) 38 antibodies and proteasome inhibitor (PI)1
Secondary endpoints:
  • Secondary endpoints included ORR, ≥CR, MRD negativity, OS, patient-reported outcomes (PROs)1
  • The ORR of patients treated with cilta-cel vs. SoC was 84.6% vs. 67.3%, with 73.1% vs. 21.8% of patients reaching ≥CR, respectively (OR=3.0; 95% CI: 1.8-5.0; p<0.0001)1
  • MRD negativity was significantly higher (OR=8.7; p<0.0001) with the cilta-cel arm at 60.6% compared with 15.6% in the SoC arm1
  • At the time of analysis, OS data were immature with 39 deaths in the cilta-cel arm vs. 47 deaths in the SoC arm (HR=0.78; 95% CI: 0.5-1.2; p=0.26)1
  • In the as-treated population (n=126), 12-month PFS was at 90% with an ORR of 99.4%, an MRD negative at 10-5 of 72% and a ≥CR rate of 86.4%1


  • In the safety population of the cilta-cel arm (n=208), serious adverse events (SAEs) of any grade were reported in 44.2%, which were similar to those in the safety population of the SoC arm (n=208) at 38.9%1
  • Neutropenia was the most common hematological adverse event (AE), occurring in 89.9% of patients in the cilta-cell arm, which was similar to that in the SOC arm (85.1%)1
  • Overall, CAR-T-specific AEs were manageable with appropriate supportive care1
  • The incidence and severity of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), movement and neurocognitive treatment-emergent adverse event (MNT) of cilta-cell were lower when used in earlier lines, suggesting improved tolerability among LEN-refractory MM patients when it is used earlier in the treatment1

“Cilta-cel has the potential to be a new SoC for patients with LEN-refractory MM after first relapse”

Dr. Binod Dhakal
Medical College of Wisconsin,
Milwaukee, Wisconsin, United States

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