Cilta-Cel Generates OS Benefit in R/R Myeloma After 1 Prior Therapy

Ying Huang, PhD

Results from a prespecified second interim analysis of the phase 3 CARTITUDE-4 study (NCT04181827) showed that treatment with ciltacabtagene autoleucel (Carvykti; cilta-cel) led to a statistically significant and clinically meaningful overall survival (OS) benefit vs standard-of-care (SOC) regimens in patients with relapsed/refractory multiple myeloma who received at least 1 prior line of therapy and were refractory to lenalidomide (Revlimid), according to announcements from Johnson & Johnson and Legend Biotech.^1,2

Additionally, safety data were found to be consistent with the approved label for the CAR T-cell therapy. These OS results will be reported at an upcoming medical meeting and submitted to global regulatory authorities for review.

"[Cilta-cel], a one-time infusion, is now the first cell therapy to significantly improve OS vs SOC for patients with myeloma as early as [the] second line," Jordan Schecter, MD, vice president and Multiple Myeloma Disease Area Leader at Johnson & Johnson Innovative Medicine, stated in a news release.¹ "As we continue to strive to change outcomes and advance care for every person living with multiple myeloma, we're excited to share these results, which add to the growing body of evidence across our portfolio of differentiated, complementary therapies that attack the disease in different ways throughout the course of a patient's journey."

“We are gratified to have observed an OS benefit with a one-time infusion of CARVYKTI in the latest analysis of the CARTITUDE-4 study,” Ying Huang, PhD, chief executive officer of Legend Biotech, added in a separate press release.² “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 battling an incurable disease.”

The open-label, randomized trial enrolled patients with lenalidomide-refractory multiple myeloma who received 1 to 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), and did not have prior exposure to a CAR T-cell therapy or BCMA-targeted therapy.³

Upon enrollment, patients were randomly assigned 1:1 to receive either a single infusion of cilta-cel after physician's choice of bridging therapy; or physician’s choice of SOC regimens, including pomalidomide (Pomalyst) plus bortezomib (Velcade) and dexamethasone (PVd) or daratumumab (Darzalex) plus pomalidomide and dexamethasone (DPd). Treatment in the control arm continued until disease progression (PD), and patients who experienced PD were not permitted to cross over to the cilta-cel arm.

The study’s primary end point is progression-free survival (PFS), with key secondary end points comprising safety, OS, overall response rate, and minimal residual disease negativity.

On April 5th, 2024, the FDA expanded the indication for cilta-cel to include adult patients with relapsed/refractory multiple myeloma who received 1 or more prior lines of therapy, including a PI or IMiD, and are lenalidomide refractory.⁴ It is currently the only FDA-approved BCMA-targeted therapy for patients in this population.

Prior results from CARTITUDE-4 supported this regulatory decision, showing that patients treated with the CAR T-cell therapy (n = 208) experienced a 59% reduction in the risk of disease progression or death compared with those treated with SOC PVd or DPd (n = 211).4 The median PFS with cilta-cel was not yet reached vs 11.8 months with SOC regimens (HR, 0.26; 95% CI, 0.18-0.38; P <.001) at a median follow-up of 15.9 months (range, 0.1-27.3).³

The toxicity profile for cilta-cel comes with a boxed warning for cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, Parkinsonism, and Guillain-Barre syndrome; associated complications such as hemophagocytic lymphohistiocytosis/macrophage activation syndrome and prolonged or recurrent cytopenias; and secondary malignancies such as acute myeloid leukemia, myelodysplastic syndrome, and T-cell malignancies.⁴

References

1. Carvykti (ciltacabtagene autoleucel) achieved statistically significant and clinically meaningful improvement in overall survival in landmark CARTITUDE-4 study. News release. Johnson & Johnson. July 2, 2024. Accessed July 2, 2024. https://www.investor.jnj.com/news/news-details/2024/CARVYKTI-ciltacabtagene-autoleucel-achieved-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-in-landmark-CARTITUDE-4-study/default.aspx
2. Legend Biotech announces positive overall survival results of landmark phase 3 CARTITUDE-4 trial in multiple myeloma. News Release. Legend Biotech. July 2, 2024. Accessed July 2, 2024. https://www.globenewswire.com/news-release/2024/07/02/2907367/0/en/Legend-Biotech-Announces-Positive-Overall-Survival-Results-of-Landmark-Phase-3-CARTITUDE-4-Trial-in-Multiple-Myeloma.html
3. San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347. doi:10.1056/NEJMoa2303379
4. Carvykti is the first and only BCMA-targeted treatment approved by the US 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 2, 2024.https://www.jnj.com/media-center/press-releases/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