Cilta-cel Improves Survival Vs Standard Therapy in R/R Multiple Myeloma

Data from the second interim analysis of the trial showed that cilta-cel produced a statistically significant and clinically meaningful OS improvement among patients who received 1 to 3 prior lines of treatment including a proteasome inhibitor and an immunomodulatory drug.

A single dose of ciltacabtagene autoleucel (cilta-cel; Carvykti) conferred an overall survival benefit (OS) benefit compared with pomalidomide (Pomalyst) plus bortezomib (Velcade) and dexamethasone (PVd) or daratumumab (Darzalex) plus pomalidomide and dexamethasone (DPd) in those with previously treated relapsed and lenalidomide (Revlimid)-refractory multiple myeloma, according to a press release on updated findings from the phase 3 CARDITUDE-4 trial (NCT04181827).¹

Data from the second interim analysis of the trial showed that cilta-cel produced a statistically significant and clinically meaningful OS improvement among patients who received 1 to 3 prior lines of treatment including a proteasome inhibitor and an immunomodulatory drug. Safety results were comparable with prior reports of the agent, and investigators observed no new safety signals.

Developers plan to present these results at a future medical meeting and share their findings with regulatory health authorities to support label updates across the world.

“We are gratified to have observed an [OS] benefit with a one-time infusion of [cilta-cel] in the latest analysis of the CARTITUDE-4 study,” Ying Huang, PhD, chief executive officer at Legend Biotech, said in the press release.¹ “This latest data point builds on the growing body of evidence from CARTITUDE-4 that shows the significant benefit [cilta-cel] offers [patients with] multiple myeloma [who have] an incurable disease.”

In the CARDITUDE-4 trial, patients were randomly assigned to receive standard therapy or cilta-cel at a target dose of 0.75 x 10⁶ CAR-positive T cells/kg.² In the comparator arm, investigators administered pomalidomide at 4 mg orally, bortezomib at 1.3 mg/m² subcutaneously, dexamethasone at 20 mg once daily orally in the PVd regimen or at 40 mg weekly in the DPd regimen, and daratumumab at 1800 mg subcutaneously.

The trial’s primary end point was progression-free survival (PFS). Secondary end points included complete response (CR) or stringent CR rate, minimal residual disease negativity, OS, overall response rate, adverse effects, and health-related quality of life.

Patients 18 years and older with measurable disease at screening and previous treatment with 1 to 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory drug were eligible for enrollment on the trial. Other eligibility criteria included having documented disease progression within 6 months following the last line of therapy, refractory disease following prior treatment with lenalidomide, and adequate clinical laboratory values.

Those with any prior BCMA-directed treatment or CAR T-cell therapy were not eligible for enrollment on the trial. Receiving treatment with a monoclonal antibody within 3 weeks or cytotoxic therapy within 2 weeks of beginning study treatment was also grounds for exclusion from enrollment.

The FDA approved cilta-cel in relapsed/refractory multiple myeloma following at least 1 prior line of therapy in April 2024.³ Supporting data for the approval came from the CARDITUDE-4 trial. Findings showed that cilta-cel conferred a 59% reduction in the risk of disease progression compared with PVd or DPd.

“[Cilta-cel] demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results. With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as the first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease,” Binod Dhakal, MD, an associate professor at the Medical College of Wisconsin in the Division of Hematology and Oncology, said in a press release at the time of the approval.³

The European Commission approved cilta-cel for the same patient population in April 2024 based on findings from CARDITUDE-4.⁴

References

1. Legend Biotech announces positive overall survival results of landmark phase 3 CARTITUDE-4 trial in multiple myeloma. News release. Legend Biotech Corporation. July 2, 2024. Accessed July 3, 2024. https://tinyurl.com/bdedb2xz
2. A study comparing JNJ-68284528, a CAR-T therapy directed against B-cell maturation antigen (BCMA), versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in participants with relapsed and lenalidomide-refractory multiple myeloma (CARTITUDE-4). ClinicalTrials.gov. Accessed July 3, 2024. https://tinyurl.com/2pc533uv
3. CARVYKTI® is the first and only BCMA-targeted treatment approved by the U.S. FDA for patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. News release. Johnson & Johnson. April 5, 2024. Accessed July 3, 2024. https://tinyurl.com/5n7zpkd9
4. CARVYKTI® (ciltacabtagene autoleucel) approved by the European Commission for second-line treatment of patients with relapsed and refractory multiple myeloma. News release. Legend Biotech Corporation. April 22, 2024. Accessed July 3, 2024. https://tinyurl.com/4j6ccjy6