New Hope for Multiple Myeloma: Cilta-Cel Improves Overall Survival

Findings from the phase 3 CARTITUDE-4 study (NCT04181827) showed that treatment with ciltacabtagene autoleucel (cilta-cel; Carvykti) led to a statistically significant and clinically meaningful improvement in overall survival (OS) among patients with relapsed and lenalidomide-refractory multiple myeloma who received 1 to 3 prior lines of therapy.¹

Updates results from the interim analysis will be presented at an upcoming medical meeting and submitted to global regulatory authorities.

"[Cilta-cel], a 1-time infusion, is now the first cell therapy to significantly improve overall survival versus standard of care for patients with myeloma as early as second line," said Jordan Schecter, MD, vice president, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine, in a press release. "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."

The CARTITUDE-4 study is investigating cilta-cel vs standard-of-care (SOC) treatments of pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or daratumumab (Darzalex), pomalidomide, and dexamethasone (DPd). The study’s primary end point is progression-free survival (PFS), and secondary end points include safety, OS, minimal residual disease (MRD) negativity rate, and overall response rate (ORR).

The first results from CARTITUDE-4 were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. At a median follow-up of 16 months (range, 0.1-27), cilta-cel reduced the risk of disease progression or death by 74% (HR, 0.26; P <.0001),meeting the primary end point of the study.² Findings published in the New England Journal of Medicine showed that PFS was not reached in the cilta-cel arm vs 11.8 months in the SOC arm (HR, 0.26; 95% CI, 0.18-0.38; P <.0001), and PFS at 12 months was 75.9% (95% CI, 69.4%-81.1%) in the cilta-cel arm vs 48.6% (95% CI, 41.5%-55.3%) in the SOC arm. Further, the ORR (84.6% vs 67.3%), complete response rate (73.1% vs 21.8%), and MRD-negative rate (60.6% vs 15.6%) were better in the cilta-cel vs SOC arms, respectively.³

Cilta-cel was originally approved by the FDA in February 2022 for the treatment of patients with relapsed or refractory multiple myeloma who had received 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and anti-CD38 monoclonal antibody.⁴

In April 2024, the FDA approved cilta-cel for the treatment of multiple myeloma that was relapsed or refractory to at least 1 prior line of therapy, including an immunomodulatory agent and a proteasome inhibitor, and refractory to lenalidomide.⁵

REFERENCES:

1. Carvykti® (ciltacabtagene autoleucel) achieved statistically significant and clinically meaningful improvement in overall survival in landmark CARTITUDE-4 study. News release. Johson & Johnson. July 2, 2024. Accessed July 2, 2024. https://tinyurl.com/yyjmu5sd

2. Dhakal B, Yong K, Harrison S, et al. First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. J Clin Oncol. 2023:41(17)LBA106-LBA106. coi:10.1200/JCO.2023.41.17_suppl.LBA106

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;389:335-347. 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://tinyurl.com/43znj9t2

5. Carvykti™ (ciltacabtagene autoleucel), BCMA-directed car-t therapy, receives US FDA approval for the treatment of adult patients with relapsed or refractory multiple myeloma. News release. February 28, 2022. Accessed February 28, 2022. https://bit.ly/3str0w9