Carvykti found effective at treating multiple myeloma in real world

Real-world treatment with the cell therapy Carvykti (ciltacabtagene autoleucel) was found to be highly effective among people with difficult-to-treat multiple myeloma in a multicenter study in the U.S.

Carvykti was approved in the U.S. in 2022 for treating adults with relapsed or refractory multiple myeloma (RRMM). However, the researchers noted that more than half of the patients in the new real-world study would not have been considered eligible for participation in the clinical trial that led to the therapy’s approval, mainly due to coexisting health conditions.

Yet nearly 90% of these patients exhibited at least a partial treatment response.

“Even though in the real world a majority of patients are not as fit in terms of performance status, organ function, or [initial] blood counts as they were in the clinical trial that led to FDA approval [of this therapy], these patients can do very well,” Surbhi Sidana, MD, the study’s first author and an associate professor at Stanford University School of Medicine, said in a press release from the American Society of Hematology (ASH).

The study, “Safety and Efficacy of Standard of Care Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma,” was published in Blood, ASH’s flagship journal.

Treating multiple myeloma patients in trials led to a 98% response rate

Carvykti, codeveloped by Legend Biotech and Janssen, is a CAR T-cell therapy wherein a patient’s immune T-cells, which have innate cancer-fighting abilities, are collected and genetically engineered to make them better able to attack and kill off myeloma cells.

The modified cells, which target BCMA, a protein found on the surface of myeloma cells, are then infused back into the patient.

The therapy was initially approved for adults with RRMM who had received four or more prior lines of treatment, including an immunomodulatory agent (iMiD), a proteasome inhibitor (PI), and a CD38 inhibitor.

The label was expanded earlier this year to include patients who had failed to respond to another approved therapy, Revlimid (lenalidomide), and who had relapsed after at least one prior treatment line, including a PI and an iMiD.

Carvykti’s initial approval was backed by data from the Phase 1b/2 CARTITUDE-1 clinical trial (NCT03548207), where the overall treatment response rate was 98%.

However, patients treated in the real world don’t always have the same characteristics as those enrolled in clinical trials. They may have a higher disease burden or more coexisting health conditions that would have left them ineligible for trial participation.

High survival rates now seen in real-world patients with coexisting conditions

To learn more about Carvykti’s impact in the real-world setting, the scientists looked at clinical outcomes from RRMM patients treated with Carvykti at 16 U.S. hospitals from March to December of 2022, shortly after the therapy’s initial approval.

A total of 255 patients started the process of having their T-cells collected to manufacture Carvykti. More than half (56%) would not have met the eligibility criteria for CARTITUDE-1, mainly due to coexisting health conditions, followed by treatment history.

In the end, 236 patients, with a median age of 64 years, ultimately received the cell therapy after a median of six prior lines of therapy. They had a generally more aggressive disease burden relative to those in CARTITUDE-1, including high-risk genetic markers (40% vs. 24%) and an aggressive form of multiple myeloma called plasma cell leukemia (6% vs. 0%).

Still, Carvykti was associated with high response rates over a median follow-up of 13 months, or slightly longer than one year. The overall treatment response rate was 89%, with 70% of patients achieving a complete response or better, meaning there are no detectable signs of cancer.

Median progression-free survival and overall survival were not reached, meaning not enough patients had experienced cancer progression to calculate the values. However, at one year, 68% of patients were estimated to have no signs of disease progression, while 82% were estimated to be alive.

Survival rates were generally better for patients who received CAR T-cells that met certain quality control standards set by U.S. regulators.

[Carvykti treatment] is feasible in a [varied] real-world population of patients with RRMM with [coexisting conditions], resulting in deep and durable responses.

Prior treatment with other BCMA-targeted therapies — an exclusion criterion in CARTITUDE-1 — was generally associated with worse treatment responses, especially for patients who had received such treatments more recently.

Safety findings were generally similar to what’s been observed in clinical trials.

Three-quarters of patients experienced cytokine release syndrome (CRS) and 14% experienced immune effector cell-associated neurotoxicity syndrome (ICANS), which are types of immune reactions associated with CAR T-cell therapies.

Moreover, 10% of patients exhibited signs of delayed neurotoxicity, which were eventually resolved for about half. However, three people died from these problems and five were still experiencing ongoing neurological issues at their last follow-up.

“Delayed neurotoxicity is predominantly seen with [Carvykti] [compared with other CAR-T therapies], and that’s another trade-off we should still be aware of,” Sidana said.

At the last follow-up, 50 patients had died, with 10% of deaths deemed unrelated to myeloma itself and instead due to infections, CRS, ICANS, delayed neurotoxicity, and secondary cancers.

Carvykti treatment “is feasible in a [varied] real-world population of patients with RRMM with [coexisting conditions], resulting in deep and durable responses,” the researchers wrote.

Still, there’s a need for “close surveillance” to monitor for complications such as delayed neurotoxicity or secondary cancers. The authors indicated that future research should focus on measures to prevent deaths related to these complications.