Idecabtagene Vicleucel in Post-Stem Cell Transplant Myeloma Patients

Dr. Saad Usmani presents an abstract on the efficacy and safety of Idecabtagene Vicleucel in clinical high-risk multiple myeloma patients with early relapse after frontline autologous stem cell transplantation. 

Abstract title:

KarMMa-2 Cohort 2a: Efficacy and Safety of Idecabtagene Vicleucel in Clinical High-Risk Multiple Myeloma Patients with Early Relapse after Frontline Autologous Stem Cell Transplantation

Purpose of the trial:

Patients with multiple myeloma (MM) who relapse early after frontline therapy with autologous stem cell transplant (ASCT) have a poor prognosis. Novel therapies are needed to improve outcomes (Paiva Blood 2012; Bygrave Br J Haematol 2020). In the pivotal phase 2 KarMMa study (NCT03361748), treatment with the B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy idecabtagene vicleucel (ide-cel) resulted in frequent, deep, and durable responses in pts with relapsed and refractory MM (RRMM) who were triple-class exposed and refractory to last treatment (Munshi N Engl J Med 2021). KarMMa-2 is a multicohort, phase 2, multicenter trial (NCT03601078) of ide-cel in RRMM and in clinical high-risk MM, defined as early relapse after frontline therapy (cohorts 2a, 2b) or inadequate response after frontline ASCT (2c). The efficacy and safety of ide-cel in cohort 2a are presented.

Video summary:

The primary efficacy endpoint was complete response (CR) rate (CRR; CR and stringent CR) by investigator per IMWG criteria. Secondary endpoints included overall response rate (ORR; ≥ partial response), time to response (TTR), duration of response (DOR), PFS, OS, safety, and pharmacokinetics (PK). Exploratory endpoints included assessment of soluble BCMA (sBCMA) level and minimal residual disease negativity (MRD–) by next-generation sequencing (<10-5 nucleated cells). Efficacy and safety were analyzed in all pts who received ide-cel; PK and sBCMA were analyzed in evaluable pts. MRD– is reported for evaluable pts with ≥CR.

Ide-cel was successfully manufactured and infused in 37/39 pts. Median age was 57 y; median time since diagnosis was 1.6 y. A total of 62.2% pts had ECOG PS 0, and 70.3% received bridging therapies (corticosteroids, alkylating agents, immunomodulatory agents, proteasome inhibitors [PI], and/or anti-CD38 antibodies) for MM. At study entry, 13.5%/51.4%/5.4% pts had R-ISS stage I/II/III disease, 32.4% had high-risk cytogenetics, 18.9% had bone marrow biopsy-determined high tumor burden (≥50% bone marrow CD138+ plasma cells), and 8.1% had extramedullary disease. Most pts had disease refractory to an immunomodulatory agent (86.5%) or PI (89.2%); 86.5% had double refractory disease.

Conclusions:

Ide-cel treatment demonstrated frequent, deep responses in pts who experienced an early relapse after frontline therapy with ASCT. MRD− was sustained in a subset of pts >18 mo. The incidence of CRS and NT were similar in these pts vs those treated with ide-cel in later lines. These results support a favorable clinical benefit-risk profile of ide-cel and its potential use in earlier lines of treatment.

Trial information:

ASH 2022: Abstract #361 (https://ash.confex.com/ash/2022/webprogram/Paper162469.html)

Authors:

Saad Usmani, MD, Krina Patel, MD, MSc, Parameswaran Hari, MD, MRCP, Jesus Berdeja, MD4, Melissa Alsina, MD, Ravi Vij, MD, MBBS6, Noopur Raje, MD, Xavier Leleu, MD, PhD, Madhav Dhodapkar, MBBS, Ran Reshef, MD, MSc, Anna Truppel-Hartmann, MD, Debashree Basudhar, PhD, Ethan Thompson, PhD, Xirong Zheng, PhD, Revathi Ananthakrishnan, PhD, Chiara Greggio, PhD, Linda Favre-Kontula, PhD, Lars Sternas, MD, PhD and Jesús San-Miguel, MD, PhD