FDA Approval Sought for Cilta-Cel in Relapsed/Refractory Multiple Myeloma


December 21, 2020 - A rolling submission of the biologics license application for the BCMA-directed CAR T-cell product ciltacabtagene autoleucel for use in adults with relapsed/refractory multiple myeloma has been initiated to the FDA.

Peter Lebowitz, MD, PhD

A rolling submission of the biologics license application for the BCMA-directed CAR T-cell product ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) for use in adults with relapsed/refractory multiple myeloma has been initiated to the FDA.1

Results from the phase 1/2 CARTITUDE-1 trial (NCT03548207), which were presented during the 2020 ASH Annual Meeting & Exposition, showed that cilta-cel elicited a high response rate with an acceptable safety profile in patients with relapsed/refractory multiple myeloma.2

Specifically, the objective response rate (ORR) with the product, when delivered at the recommended phase 2 dose, was 96.9%; this was comprised of a stringent complete response (sCR) rate of 67.0%, a very good partial response (VGPR) rate of 25.8%, and a partial response rate of 4.1%.

“We are committed to innovation in cell therapy and advancing the science of multiple myeloma to improve patients’ lives,” Peter Lebowitz, MD, PhD, global therapeutic area head of Janssen Research & Development, LLC, stated in a press release. “Today’s milestone is the culmination of a remarkable clinical development effort and collaboration with Legend Biotech. We look forward to working with the FDA in their review of cilta-cel with the goal of bringing a highly-active, dual-binding BCMA CAR T therapy to patients with relapsed and/or refractory multiple myeloma who are in need of new treatment options.”

In the phase 1b/2 trial, investigators set out to examine the safety and efficacy of cilta-cel in patients with progressive multiple myeloma defined by International Myeloma Working Group criteria who had received at least 3 previous therapies—including an immunomodulatory drug, a proteasome inhibitor, and a CD38-targeted therapy—or who are double refractory. Moreover, patients had to have an ECOG performance status of 0-1.

Patients were screened and enrolled to the study and then underwent apheresis and bridging therapy, if needed. Once completed, they received lymphodepleting chemotherapy comprised of cyclophosphamide given at a dose of 300 mg/m2 and fludarabine given at a dose of 30 mg/m2 on days -5 to -3 before they underwent CAR T-cell infusion.

The target dose was 0.75 x 106 viable CAR-positive T cells/kg, and the median dose given was 0.71 x 106(range, 0.51-0.95 x 106).

The primary end points of the phase 1b portion of CARTITUDE-1 was to understand the safety of the product and identify the recommended phase 2 dose, while the primary objective in the second phase of the trial was to examine the efficacy of cilta-cel by evaluating ORR.

Earlier results from the phase 1b portion of the trial presented during the 2020 ASCO Virtual Scientific Program indicated that cilta-cel elicited responses in all 29 participants who received it; this included a very good partial response or higher rate of 97%.3

The data presented at ASH comprised all patients who received treatment with the CAR T-cell product in both phases of the trial (n = 97). The majority of the participants, or 86%, remain on trial. The median time for the manufacturing of the product was 29 days and no patients were found to discontinue from the study because of manufacturing failure.

Additional results from the trial revealed that 72.2% of patients were still responding to treatment at the time of data cutoff, and the median time to first response was 1 month. Moreover, the minimal residual disease (MRD) negativity rate at 10-5 was 93.0% among 57 evaluable patients; this represented 54.6% of the total study population. Thirty-four percent of patients (n = 33) achieved a sCR and MRD negativity.

The median progression-free survival (PFS) had not yet been reached in those who responded to the CAR T-cell product. The 1-year PFS rate was 76.6%; in those who experienced a sCR, the 1-year PFS rate was 84.5%, while it was 68.0% in those who had a VGPR. Additionally, the 1-year overall survival (OS) rate was 88.5%, and the median OS had not yet been reached.

Regarding safety, the most frequently reported grade 3/4 toxicities were hematologic and were experienced by 99.0% of patients: these included neutropenia (94.8%), anemia (68.0%), leukopenia (60.8%), and thrombocytopenia (59.8%). A little more than half of patients, or 57.7%, experienced any-grade infections; the most common grade 3/4 infections included pneumonia (8.2%) and sepsis (4.1%).

Cytokine release syndrome (CRS) was experienced by 94.8% of patients at any grade; however, only 4.1% of these effects were grade 3/4. Approximately 69% of patients required tocilizumab (Actemra), while 21.6% needed corticosteroid support. The majority, or 98.9% of patients had their CRS resolve within 2 weeks of onset.


  1. Janssen initiates rolling submission of a biologics license application to US FDA for BCMA CAR-T therapy ciltacabtagene autoleucel (cilta-cel) for the treatment of relapsed and/or refractory multiple myeloma. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. December 21, 2020. Accessed December 21, 2020. http://prn.to/2WxQ7x4.
  2. Madduri D, Berdeja JG, Usmani SZ, et al. CARTITUDE-1: phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen–directed chimeric antigen receptor T cell therapy, in relapsed/refractory multiple myeloma. Blood. 2020;136(suppl 1):22-25. doi:10.1182/blood-2020-136307
  3. Berdeja JG, Madduri D, Usmani SZ, et al. Update of CARTITUDE-1: A phase Ib/II study of JNJ-4528, a B-cell maturation antigen (BCMA)-directed CAR-T-cell therapy, in relapsed/refractory multiple myeloma. J Clin Oncol. 2020;38(suppl 15):8505. doi:10.1200/JCO.2020.38.15_suppl.8505
Recent Videos
Manali Kamdar, MD, on Liso-Cel's Ongoing Benefit in the Treatment Lanscape for LBCL
Steve Kanner, PhD, the chief scientific officer of Caribou Biosciences
David Dimmock, MBBS, on AI-Guided ASO Development for Ultra-Rare Diseases
Manali Kamdar, MD, on The Importance of Bringing Liso-Cel to Earlier Lines of Lymphoma Treatment
Subhash Tripathi, PhD, on Generating In Vivo CARs With A2-CAR-CISC EngTreg Cells
Luke Roberts, MBBS, PhD, on Challenges in Developing Gene Therapy for Heart Failure
Steve Kanner, PhD, the chief scientific officer of Caribou Biosciences
Lisa Nieland on Slowing Tumor Growth in Glioblastoma With Novel AAV Therapy
Manali Kamdar, MD, on Acclimating to Routine CAR T Practice in the Field
Leigh Ramos-Platt, MD, on Looking Forward to Gene Therapy’s Growth
© 2024 MJH Life Sciences

All rights reserved.