Cilta-Cel Provides Sustained Efficacy and Safety in Relapsed/Refractory Multiple Myeloma


Nikhil C. Munshi, MD, discusses the significance of the FDA approval of cilta-cel in patients with multiple myeloma, shares the long-term findings from the pivotal CARTITUDE-1 trial, and highlights future directions for CAR T-cell therapy in this disease.

Nikhil C. Munshi, MD

Nikhil C. Munshi, MD

The CAR T-cell therapy ciltacabtagene autoleucel (cilta-cel; Carvykti) continues to generate responses with a tolerable safety profile in patients with relapsed/refractory multiple myeloma, according to Nikhil C. Munshi, MD, who emphasized that updated findings with the agent in this population support the development of CAR T-cell products in earlier multiple myeloma treatment lines.1

Two-year follow-up data from the phase 1b/2 CARTITUDE-1 trial (NCT03548207) of cilta-cel in patients with relapsed/refractory disease showed an overall response rate (ORR) of 97.9% (95% CI, 92.7%-99.7%) and a stringent complete response (sCR) rate of 82.5% (95% CI, 73.4%-89.4%). The 27-month progression-free survival (PFS) and overall survival (OS) rates were 54.9% (95% CI, 44.0%-64.6%) and 70.4% (95% CI, 60.1%-78.6%), respectively.1 Final results of CARTITUDE-1, which were presented at the 2023 EHA Congress, demonstrated that at a median follow-up of 33.4 months (range, 1.5-45.2), cilta-cel continued to elicit an ORR of 97.9% (95% CI, 92.7%-99.7%), including an sCR rate of 82.5% (95% CI, 73.4%-89.4%).2

“[These findings] bring [cilta-cel] into prominence as a [treatment] to look forward to for patients with relapsed/refractory disease,” Munshi said.

In an interview with OncLive®, Munshi discussed the significance of the FDA approval of cilta-cel in patients with multiple myeloma, shared the long-term findings from the pivotal CARTITUDE-1 trial, and highlighted future directions for CAR T-cell therapy in this disease.

Munshi is the director of Basic and Correlative Science at the Jerome Lipper Multiple Myeloma Center, the Kraft Family Chair, the director of Multiple Myeloma Immune Effector Cell Therapy, and a senior physician at Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

OncLive: What was the goal of studying CAR T-cell therapy in a heavily pretreated multiple myeloma population in CARTITUDE-1?

Munshi: The study was focused on patients with relapsed/refractory myeloma who were exposed to a proteasome inhibitor, an immunomodulator, and an anti-CD38 therapy [and were] resistant to their last line of therapy. [This was] an advanced patient population. The plan was [like that of] most CAR T-cell studies where we collected the cells and produced CAR T cells, which took 4 to 6 weeks. Then, patients got lymphodepletion [followed by] CAR T cells, and we followed them.

Prior results from this study led to the FDA approval of cilta-cel in patients with relapsed/refractory multiple myeloma following at least 4 prior lines of therapy. What has been the significance of that approval?

The results that led to this approval were outstanding. The ORR, which remains [similar] at a median follow-up of 33.4 months, was 97%. Almost all patients responded. Previously [reported data from this trial] showed a long PFS; the median had not yet been reached. Based on [those data], patients have access to [cilta-cel]. It has become an important treatment for patients with relapsed/refractory disease. In many patients, it’s a life-saving [drug] when [all other agents] stop working. This treatment provides complete remission approximately 80% of the time.

What were the long-term follow-up findings from this trial?

These patients had a median of 6 lines of treatment and [were treated with cilta-cel at a median of] 6 years from their diagnosis. In total, 87.6% of these patients were refractory to 3 drugs. With a 97.9% response rate, the median PFS is 34.9 months, almost 3 years. In other patients with similar backgrounds [regarding previous] treatments and other [characteristics], the expected median PFS is in the range of 4 to 5 months maximum, and [the expected median] OS is 12 months. In this study, the median OS has not been reached, and at 30 months, the [estimated OS rate] is 62.9%. Durable responses were observed here.

Have any new safety signals been reported with cilta-cel in this population?

So far, no additional safety concerns have been observed. No new neurotoxicity has been observed. As part of the standard accumulation of data, second primary [disease was] observed. Six [instances of second primary disease] were observed in 4 patients. But [we saw] nothing out of line. Overall, 10 patients had hematologic issues with either myelodysplastic syndrome or acute myeloid leukemia.

Cilta-cel is under investigation in the phase 3 CARTITUDE-4 trial (NCT04181827)in patients with multiple myeloma. What other next steps are necessary for the development of cilta-cel in this disease?

CARTITUDE-4 established that cilta-cel is also effective in earlier lines of treatment. That’s where we will begin to jump. What will be exciting are the ongoing studies where, for example, cilta-cel is being compared with transplant. Can it provide durable and deep responses similar to [those achieved with] transplant? That would be a game changer if true [because] we would switch to CAR T-cell therapy instead of doing transplant.

[CAR T-cell therapy] will also be part of the standard treatment even in the older patient population. One advantage of CAR T-cell therapy is that it’s better tolerated than transplant. Instead of stopping [treatment] at 70 years of age, in clinical studies, cilta-cel, and similarly, idecabtagene vicleucel [ide-cel, Abecma], have been used in patients who are 79 and 80 years. Early utilization and utilization in an elderly patient population [may be the next steps for CAR T-cell therapy].

How can clinicians work to improve access to CAR T-cell therapies such as cilta-cel, especially as this agent advances into earlier lines of treatment?

Access has been the problem. At our big, major centers, we each have only a few patients we can treat in a month. What is beginning to change is that the companies have likely [taken steps such as] expanding their production facilities. With need comes supply, and that has increased. We are beginning to get more [treatment] slots with less waiting time. We used to have 100 patients on the waiting list, and now that list is much smaller. For the right patients, we can [begin CAR T-cell therapy] quickly. There are also 2 CAR T-cell therapies available now, so that’s a plus, and hopefully many more will come, which will ease the shortage.

What is your main message for colleagues regarding the long-term data with cilta-cel in CARTITUDE-1?

CAR T-cell therapy is extremely effective. The toxicity is manageable, so its utilization in patients, even in elderly patients, should become an important component of their therapeutic treatment. I see [the potential for] CAR T-cell therapy in combined immunotherapeutic approaches, and CAR T-cell therapy plus bispecific immunomodulators may become the standard of care and will likely be a curative treatment in myeloma.

What other data were you excited to see at the 2023 EHA Congress?

The main things to look for are the other CAR T-cell products and the bispecific antibodies. Each of them provides high response rates. Many good products were presented, each with similar results. It’s exciting that they all work.

Disclosures: Dr Munshi reports consulting or advisory roles with AbbVie, Adaptive Biotechnologies, Amgen, BeiGene, BMS, Celgene, Janssen, Karyopharm Therapeutics, Novartis, OncoPep, Raqia, Sebia, and Takeda; and patients, royalties, other intellectual property, stock, or other ownership interests with OncoPep and Raqia Therapeutics.


  1. Martin T, Usmani SZ, Berdeja JG, et al. Ciltacabtagene autoleucel, an anti-b-cell maturation antigen chimeric antigen receptor t-cell therapy, for relapsed/refractory multiple myeloma: cartitude-1 2-year follow-up. J Clin Oncol. 2023;41(6):1265-1274. doi:10.1200/JCO.22.00842
  2. Munshi N, Martin T, Usmani SZ, et al. CARTITUDE-1 final results: phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma. Presented at: 2023 EHA Congress; June 8-11, 2023; Frankfurt, Germany. Abstract S202.

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