Can Cilta-Cel Redefine Outcomes in Multiple Myeloma?

The term curative has seldom been used in the context of relapsed/refractory multiple myeloma (R/R MM), until recently. In the CARTITUDE-1 trial (NCT03548207), a single infusion of ciltacabtagene autoleucel (cilta-cel; Carvykti, Janssen Biotech, Inc/Legend Biotech) led to durable remissions without the need for maintenance therapy in patients with heavily pretreated R/R MM, raising the possibility of curative outcomes in advanced disease.¹

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However, despite these promising data, experts are cautious about labeling the therapy a cure. Many view these results as a turning point in how long-term remission is defined and pursued—particularly as cilta-cel is studied in earlier lines of therapy.

“The CARTITUDE-1 data, presented at EHA [European Hematology Association 2025 Congress], showed that 30% of patients treated with CAR T, specifically cilta-cel, are still without disease relapse at 5 years,” said Victoria Nachar, PharmD, BCOP, of Michigan Medicine in Ann Arbor, in an interview with Pharmacy Times. “The New York Times had a same-day article about it going around, using that word: cure. I think that’s really important for patients, especially in MM, because that’s not a word we ever use.”²

Cilta-Cel

Over the past 2 decades, advancements in MM treatment have significantly extended survival, with many patients now living up to 10 years after their diagnosis. However, a major challenge remains: Therapeutic responses typically weaken with each successive line of treatment, particularly in advanced disease. Chimeric antigen receptor (CAR) T-cell therapies have revolutionized outcomes for patients, demonstrating significant efficacy and safety.

CAR T-cell therapy is a novel, advanced immunotherapeutic approach that utilizes a patient’s T cells and modifies them to attack cancer cells and slow disease progression. It increases patients’ survival and quality of life. The goal is to harness a patient’s immune system to recognize and target cancer cells, offering better sensitivity and specificity, limiting damage to healthy cells, and personalizing treatment. CAR T cells are manufactured to target specific overexpressed proteins on the surface of myeloma cells.³

BCMA is highly prevalent overexpressed protein found in approximately 90% of patients with MM, making it a key therapeutic target in the treatment of R/R MM. Research has established that BCMA plays a critical pathological role in the development of several hematologic malignancies
outside of MM, making it the most popular and well-studied therapeutic target of CAR T-cell therapy. Cilta-cel is designed to bind to BCMA to activate T cells, causing them to multiply and attack the tumor. Once activated, the CAR T cells release proteins such as CD3ζ, which mimic normal immune signaling and drive further T-cell activation and expansion. These activated T cells then produce inflammatory cytokines (eg, TNF-α, IFN-γ, IL-2, and IL-6), which help kill cancer cells and recruit other immune cells to the tumor site.^3,4

Cilta-cel is 1 of 2 FDA-approved BCMA-targeting CAR T-cell therapies, alongside idecabtagene vicleucel (ide-cel, Abecma; Celgene Corporation/Bristol Myers Squibb). It received initial FDA approval in 2022 for adult patients with R/R MM who had received 4 or more prior lines of therapy. In 2024, the drug’s indication was expanded to include patients with at least 1 prior line of treatment. These approvals were supported by data from the phase 1b/2 CARTITUDE-1 trial, an open-label, multicenter study that evaluated the safety and efficacy of cilta-cel in patients with R/R MM who had received at least 3 prior lines of therapy and were triple-class exposed. The study reported promising results with an overall response rate (ORR) of approximately 98% and a median duration of response of 21.8 months.^3,5

CARTITUDE-1 Study Design

CARTITUDE-1 evaluated the safety and efficacy of cilta-cel in patients with heavily pretreated R/R MM. The trial consisted of 2 phases: Phase 1b focused on determining the recommended phase 2 dose, and phase 2 evaluated the efficacy of cilta-cel at that dose.^1,5

The primary end points were safety (phase 1b) and ORR (phase 2), as well as additional end points including overall survival, minimal residual disease (MRD), and progression-free survival (PFS). Safety was defined as the number of participants with adverse events as per severity, which is graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. ORR was defined as the percentage of participants who achieved partial response (PR) or better according to International Myeloma Working Group criteria.^1,5

The trial enrolled a total of 97 patients with R/R MM who received 3 or more prior lines of therapy and were triple-class exposed. Of the population, 97% (n = 94) were refractory to daratumumab, 25.3% (n = 23) had high-risk cytogenetics, 13.4% (n = 13) had extramedullary plasmacytomas, and 87.6% (n = 85) were triple-class refractory. All patients were treated with a single infusion of cilta-cel.⁵

CARTITUDE-1 Results

At the median follow-up of 61.3 months, 33% of patients were alive and progression-free without the need for maintenance treatment 5 or more years after cilta-cel infusion. Of the population, 96.9% achieved stringent complete response (sCR) as their best response, according to independent review committee assessments. Forty-six (47%) had progressive disease (PD) within 5 years; of the remaining 19, 17 died without PD, and 2 were lost to follow-up.⁵

“The plateau of the [PFS] curve demonstrates that long-term durable remissions in patients with heavily pretreated R/R MM are possible while emphasizing the continued goal of translating this benefit to a broader set of patients while mitigating the acute and potential long-term toxicities of cilta-cel,” said Matthew M. Lei, PharmD, BCOP, clinical pharmacy specialist, lymphoma, at Massachusetts General Hospital in Boston and editorial advisory board member for Pharmacy Practice in Focus: Oncology, in an email interview with Pharmacy Times.²

MRD-negativity results were favorable. Of the patients who achieved sCR, 12 at one facility had PET-CT and serial MRD evaluations; all (100%) were imaging-negative at year 5 or later following cilta-cel and were MRD negative (at least 10–5 threshold).⁵

“Furthermore, characteristics associated with a greater than or equal to 5-year [PFS] support the earlier use of cilta-cel in patients with lower tumor burden, emphasizing the importance of effective bridging therapy to optimally debulk prior to CAR T-cell infusion,” Lei said.²

Caution Over Cure

Using the word cure in the context of MM is controversial. Experts spoke with Pharmacy Times, sharing key insights about what these results mean and whether the data support cilta-cel as an established curative approach for MM.

“Historically in heme malignancies, the 5-year mark has been considered the transition point from remission to potential cure. So that word cure is being tossed around, especially on social media. I’ve used it myself—with a question mark. I think we need to be cautious about marketing it as a cure,” said Gabe Hinojosa, PharmD, BCOP, clinical pharmacy specialist, oncology/hematology, UT Southwestern in Dallas, Texas, in an interview with Pharmacy Times.²

“As we move from 5-year to 10-year data, we’ll better understand the durability of these responses. If patients are still in remission at the 10-year mark, it would be hard to argue against calling it a cure.”²

Experts express hesitancy, claiming there is a need for longer follow-up data before driving forward the denotation of cilta-cel as a curative agent. Without more data to validate these initial findings, sensationalizing cilta-cel as a cure for MM may be misleading.

“We don’t say that word—we don’t throw it around, even with cilta-cel. We still need to see longer-term data, because we know that even in [MM], with drugs like lenalidomide, patients can relapse 10 to 15 years later,” Nachar explained. “It’s kind of like breast cancer: You can be disease-free for 10 years, but it’s one of those solid tumors where you still worry, right? I do think CAR T, specifically cilta-cel, is changing the game in myeloma, and I hope we’ll be able to use the word cure in the future. But I still think it’s premature.”²

Next Steps

Longer follow-up is crucial to better understand and validate whether cure can be used in association with cilta-cel. The initial results hold significant promise and offer a hopeful glimpse into the future of MM care. Experts agree that more time and evidence are needed before cilta-cel can be confidently described as curative. These results highlight the therapy’s potential to deliver deep, long-lasting responses—even in heavily pretreated patients—but also underscore the need for caution, context, and further research.

As follow-up data from CARTITUDE-1 and ongoing trials in earlier treatment lines mature, pharmacists and oncology professionals will be watching closely. The coming years will determine whether cilta-cel and CAR T-cell therapy more broadly can redefine what long-term remission and possible cure look like in MM.

“We need more follow-up [data] to know the best timing [for administering the therapy] and what long-term outcomes look like,” Nachar said. “It’s just too early to throw around the C word.”²

REFERENCES

1. A study of JNJ-68284528, a chimeric antigen receptor T cell (CAR-T) therapy directed against B-cell maturation antigen (BCMA) in participants with relapsed or refractory multiple myeloma (CARTITUDE-1). Updated April 2, 2024. Accessed July 10, 2025. https://www.clinicaltrials.gov/study/NCT03548207#study-overview

2. Gerlach A. Cilta-cel spurs remission milestone—But is it a cure? Pharmacy Times. July 1, 2025. Accessed July 10, 2025. https://www.pharmacytimes.com/view/cilta-cel-spurs-remission-milestone-but-is-it-a-cure-

3. Gerlach A. Single infusion of cilta-cel yields 5-year progression-free survival in multiple myeloma. Pharmacy Times. June 9, 2025. Accessed July 10, 2025. https://www.pharmacytimes.com/view/single-infusion-of-cilta-cel-yields-5-year-progression-free-survival-in-multiple-myeloma

4. Chekol Abebe E, Yibeltal Shiferaw M, Tadele Admasu F, Asmamaw Dejenie T. Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. Front Immunol. September 2, 2022. doi:10.3389/fimmu.2022.991092

5. Jagannath S, Martin T, Cohen A, et al. Long-term (≥5-Year) remission and survival after treatment with ciltacabtagene autoleucel in CARTITUDE-1 patients with relapsed/refractory multiple myeloma. June 3, 2025. doi:10.1200/JCO-25-00760