In an interview with Targeted Oncology, Yi Lin, MD, PhD, discussed the phase 1b/2 CARTITUDE-1 study of ciltacabtagene autoleucel for the treatment of patients with relapsed or refractory multiple myeloma.
Treatment with ciltacabtagene autoleucel (cilta-cel; Carvykti) led to a longer median progression-free survival (PFS) and led to deep and durable efficacy outcomes compared with the standard of care for the treatment of patients with relapsed or refractory multiple myeloma, according to long-term findings from the phase 1b/2 CARTITUDE-1 study (NCT03548207).
Cilta-cel is a BCMA-targeted chimeric antigen receptor (CAR) T-cell therapy. In the CARTITUDE-1 study, the agent demonstrated deep and durable responses among a heavily pretreated group of patients with relapsed/refractory multiple myeloma. The overall response rate was 97% (95% CI, 91.2%-99.4%), which included stringent complete response in 67% of patients, according to data published in The Lancet.
Additionally, the risk/benefit profile of cilta-cel remained favorable with longer follow-up.For safety, cilta-cel was manageable and no new cilta-cel-related cytokine release syndrome was observed.
“This is a 1-time dose of CAR T, and then patients are just monitored. So, to be treatment-free for close to 3 years on average, is very impressive,” Yi Lin, MD, PhD, told Targeted OncologyTM, in an interview.
In the interview, Lin, a hematologist/oncologist;consultant, Division of Hematology, Department of Internal Medicine; enterprise leader, Cancer Regenerative Medicine, Biotherapeutics, and Biomanufacturing, Mayo Clinic Comprehensive Cancer Center; associate medical director, Center for Regenerative Biotherapeutics; and consultant, Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, further discussed the phase 1b/2 CARTITUDE-1 study of cilta-cel for the treatment of patients with relapsed or refractory multiple myeloma.
Targeted Oncology: Can you provide some background on cilta-cel and its use in relapsed/refractory multiple myeloma?
Lin: Cilta-cel, also known as Carvykti, is a regulatory approved CAR T is an autologous CAR T that is made from a patient's own white blood cells, a subgroup of white blood cells called T cells. B cells are genetically changed to be able to target cells that have BCMA or B-cell maturation antigen markers. And plasma cells, particularly myeloma cells, can have a relatively higher expression of these markers on them. CARTITUDE-1 is the first registration study that led to the FDA approval where they're used in the United States. In this particular trial, patients with multiple myeloma who have had at least 3 prior lines of treatment, and the main backbone of myeloma treatment, which includes a proteasome inhibitor, an image or immunomodulatory drug and a CD38 targeting monoclonal antibody.
Based on those initial primary results, which [are] already published and peer reviewed, [the] FDA has approved its use now in the United States. The approval is for patients who've had 4 prior lines of therapy, including exposure to those drugs that I had talked about.
What update can you provide on the CARTITUDE-1 trial?
[In] the final analysis of the registration trial CARTITUDE-1 study, patients with relapsed/refractory multiple myeloma received a single dose of cilta-cel and then were monitored. We already know from the primary analysis which has been published, that the response rate is very high for these patients. Ninety-eight percent of patients had some response and close to 83% of these patients had deep responses or a stringent complete response. So, up until this year, we have not seen that median progression-free survival. We looked at 1 year, we looked at 2 years, and we looked at close to 2 and a half years. The PFS rate remains quite high, and there was no median PFS. Now this year was close to 33 months of follow up close to 3 years of follow up.
Naturally, we now see that the survival follow up is mature enough. The median PFS for patients under study was close to 3 years or 35 months. That is very impressive for any therapy in multiple myeloma, particularly in the late-line setting, because all the other treatments we have are continuous treatment until the patient's progress. This is a 1-time dose of CAR T, and then patients are just monitored. To be treatment free for close to 3 years on average is very impressive.
What we're also seeing is because we do know there are patients who had that deep response, including for some patients who were what we call MRD negative, so even deeper, minimal residual disease checks for those patients, the PFS or even longer.
What do these findings mean as we use cilta-cel in the clinic? What other clinical trials are ongoing to further support the use of CAR T-cell therapy in this disease?
As you know, this is a very exciting time for the field of multiple myeloma, we're having more and more treatment options, including immunotherapy options, which are some of the most exciting ones, just seeing the response rate and even the PFS duration for many of these patients. So, we're certainly very glad to see so cilta-cel has been FDA approved.
In the first year in transition to clinical practice, there were a lot of challenges with manufacturing access for this in the practice. But in the very recent months, we're seeing some improvements. We hope that will translate into more access for our patients. What we are seeing now with clinical trial results that were reported at ASCO are also very exciting. [This was a] randomized control study comparing cilta-cel with other standard of care therapy options for myeloma patients in earlier line settings. That also matters for the primary end point of showing that patients who received cilta-cel had longer PFS. And so, we're anticipating that FDA will review that and either, you know, by the end of this year beginning next year, hopefully we'll have a decision on if the CAR T can move into earlier-line setting for these patients.
There are ongoing trials for cilta-cel also now in the frontline setting, we're seeing some very encouraging signals for how this CAR T is performing, both for patients who have very early relapse after first-line therapy or not the most ideal response to first-line therapy, or even as part of the first-line therapy. So, there is plan to open a randomized control study as well to formally compare cilta-cel with standard of care treatment options, even in the frontline setting.
What other clinical trials are showing continue to show the utility of CAR T-cell therapy in relapsed/refractory multiple myeloma.
This is an exciting time for the field of multiple myeloma. We're having more and more treatment options, including immunotherapy options, which are some of the most exciting ones, and [we are] just seeing the response rate and even the PFS duration for many of these patients. We're very glad to see that cilta-cel has been FDA-approved. In the first year in transition to clinical practice, there were a lot of challenges with manufacturing access for this in the practice. But in the recent months, we're seeing some improvements. We hope that will translate into more access for our patients.
What we are also seeing was with clinical trial results that were reported at ASCO in a randomized, controlled study comparing cilta-cel with other standard of care therapy options for patients with myeloma in earlier lines. That also met its primary end point of showing that patients who received cilta-cel had longer PFS rates. We are anticipating that the FDA will review that, either by the end of this year or beginning next year. Hopefully we'll have a decision on if CAR T can move into earlier-line settings for these patients.
There are ongoing trials for cilta-cel now in the frontline setting. We're seeing some encouraging signals for how this CAR T is performing, both for patients who have very early relapse after first-line therapy or not the most ideal response to first-line therapy, or even as part of the first-line therapy. There is a plan to open a randomized, controlled study as well, to formally compare cilta-cel with standard of care treatment options, even in the frontline setting.
How else do you think this will be sequenced in the future?
I think the sequencing question is interesting because we think there is value in using CAR T therapy earlier, including frontline, in that hopefully the patient's own immune cells are not so beat up by treatment, and that they might be more effective upfront. We also know there are other immunotherapy options. There's been a lot of exciting data with bispecific antibodies, and we are learning the logistics of how it's given. Some of these [adverse] effects are different, so there'll be some ongoing studies to understand those better and how to balance the clinical response and the [adverse] effects, but bispecific antibodies being a therapy that could potentially combine with other drugs would also be moving into the frontline setting. Understanding how best to sequence and use both of these treatment modalities will be an important question for clinical trials.