N Engl J Med 2023 Jun 05
Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma.
Abstract
Background
Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR-T cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease.
Methods
In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival.
Results
A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%).
Conclusions
A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.).
Related Questions
What are your top takeaways in Myeloma from ASH 2025?
As is probably true for most multiple myeloma-focused investigators, my interest was most piqued by the results of the MajesTEC-3 trial, which demonstrated an 83% 3-year progression-free survival in a population of patients with relapsed or refractory disease resulting from teclistamab and daratumum...
After the MAJESTEC-3 results, what is your approach to choosing between tec-dara vs. cilta-cel versus another triplet for multiple myeloma in first relapse?
This is an excellent question, and literally a million-dollar question for various companies involved. It's worth noting that the US FDA can change the package insert at will (and has done so) compared to what the trials did, so there's no guarantee as of yet that Tec-Dara (based on MajesTEC-3) will...
What is your approach to determining fitness for patients to undergo CAR-T therapy for relapsed/refractory multiple myeloma, and any absolute perceived contraindications for CAR-T?
This is a great question to which the only truly correct answer is, "It depends." Not just on the patient & disease biology, of course, but also the year in which the question is answered. For example, right now there are patients for whom commercial cilta-cel or ide-cel are not appropriate because ...
What are your top takeaways in Hematologic Malignancies from ASCO 2024?
Always an exciting conference for myeloma and this year was no exception.1. IMROZ study: The management of newly diagnosed multiple myeloma (NDMM) has evolved significantly over the past few years. One of the first clinical assessments in planning treatment is determining eligibility for autologous ...
What are your top takeaways in Hematologic Malignancies from ASCO 2023?
There was a time when those of us in the myeloma field could focus on ASH each year as our main source of updated practice-changing abstracts. No longer! Many exciting oral and poster abstracts were presented around multiple myeloma at the 2023 ASCO meeting in Chicago. Here are the top three that st...
Would you implement CAR-T therapy earlier in practice if approved in earlier lines for multiple myeloma based on the KarMMa-3 and CARTITUTUDE-4 studies?
I agree with @Dr. First Last's excellent take on CARTITUDE-4 and KarMMA-3. For patients who have had 2 prior lines of therapy, I am absolutely going to reach for CAR-T (or bispecific antibodies as their earlier-line studies get published) with an emphasis on cilta-cel based on the data at hand.But w...