Cilta-Cel May Lower Risk of Disease Progression or Death in R/R Multiple Myeloma

Joshua Richter, MD

The phase 3 CARTITUDE-4 study (NCT04181827) of ciltacabtagene autoleucel (Carvyktil; cilta-cel) vs pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd) for patients with relapsed and lenalidomide-refractory multiple myeloma has met its primary end point of significant improvement in progression-free survival (PFS), according to data from the first prespecified interim analysis.¹

With the primary end point met, the independent data monitoring committee recommends the unblinding of the study.

“Based on the previous FDA approval of cilta-cel, we know that this therapy has impressive efficacy in patients with heavily/advanced relapsed myeloma. CARTITUDE-4 addresses its role in an earlier relapse setting, 1-3 prior lines of therapy. This will hopefully lead to providing access to early-line patients for not only a highly effective therapy, but also a ‘one and done’ option that does not require continual or long-term treatment. We anxiously await the granular details likely to be presented at upcoming meetings such as the ASCO Annual Meeting,” Joshua Richter, MD, associate professor of medicine in the Tisch Cancer Institute, division of Hematology/Oncology at Mount Sinai, told Targeted Oncology™.

Cilta-cel is a BCMA-directed, genetically modified autologous T-cell immunotherapy. The agent works by reprogramming a patient's T-cells with a transgene encoding chimeric antigen receptor (CAR) which then directs the CAR positive T-cells to eliminate cells that express BCMA.

Previously in February 2022, cilta-cel was granted approval from the FDA for the treatment of adults with relapsed or refractory multiple myeloma after 4 or more prior lines of therapy. This approval included those who received a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

The randomized, phase 3 CARTITUDE-4 is the first of its kind to assess the efficacy and safety of cilta-cel. In the study, investigators are comparing treatment with cilta-cel with standard of care treatments of either PVd or DPd in adult patients with relapsed and lenalidomide-refractory multiple myeloma.² To be enrolled in the study, patients must have received 1-3 prior lines of therapy.

In experimental arm A, patients will be given oral pomalidomide at 4 mg, bortezomib at 1.3 mg/m² administered subcutaneously (SC), and oral dexamethasone at 20 mg/day or 10mg/day for patients older than 75 years of age which will be administered orally in PVd treatment and orally or via intravenous (IV) administration at 40 mg weekly or 20mg weekly for participants older than 75 years of age in DPd treatment.

Patients in experimental arm B, patients will receive at least 1 cycle of bridging therapy of PVd or DPd. Additional cycles of bridging therapy may be considered based on one's clinical status and timing of availability of cilta-cel, a conditioning regimen, and cilta-cel. Cilta-cel infusion Patients will be administered cilta-cel at a dose of 0.75 106 CAR-positive viable T cells/kg.

Enrollment is open to patients aged 18 years and older with measurable disease at the time of screening, those who have received 1-3 prior lines of therapy, and documented evidence of progressive disease.

The primary end point of the study is PFS, and the secondary end points of the trial consist of safety, overall survival, minimal residual disease negative rate, and overall response rate.

Patients will continue to be followed for all the end points for the duration of the study.

Findings from CARTITUDE-4 are expected to be presented at an upcoming scientific congress. Results will also be shared with health authorities in planned submission applications.

“Cilta-cel is following the traditional path in myeloma of FDA approval in late line, evaluation in early relapse, and evaluation in newly diagnosed patients. The next steps are to evaluate this type of therapy as part of an upfront strategy, either following an autologous stem cell transplant [as post-transplant consolidation] or completely replacing transplant,” explained Richter. “The hope remains that some combination of interventions, potentially including a CAR T, may be the key to curing myeloma.”

REFERENCES:

Janssen announces unblinding of phase 3 CARTITUDE-4 study of CARVYKTI® (cilta-cel) as primary endpoint met in treatment of patients with relapsed and refractory multiple myeloma. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. January 27, 2023. Accessed January 27, 2023. https://prn.to/3Hym68T

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. Updated January 18, 2023. Accessed January 27, 2023. https://clinicaltrials.gov/ct2/show/NCT04181827