Safety and efficacy of standard of care (SOC) ciltacabtagene autoleucel (Cilta-cel) for relapsed/refractory multiple myeloma (RRMM).

Authors

null

Doris K. Hansen

Department of Blood & Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL

Doris K. Hansen , Krina K. Patel , Lauren C. Peres , Mehmet H. Kocoglu , Leyla Shune , Gary Simmons , Christopher J. Ferreri , Shebli Atrash , Ricardo Daniel Parrondo , Saurabh Chhabra , Patrick Costello , Shonali Midha , Melissa Alsina , Peter M. Voorhees , Myo Htut , Douglas W. Sborov , Jack Khouri , Murali Janakiram , Yi Lin , Surbhi Sidana

Organizations

Department of Blood & Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, MD Anderson Cancer Center, Houston, TX, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, Division of Hematologic Malignancies and Cellular Therapeutics (HMCT), University of Kansas Medical Center, Kansas City, KS, Virginia Commonwealth University Massey Cancer Center, Richmond, VA, Levine Cancer Institute, Charlotte, NC, Mayo Clinic Florida, Jacksonville, FL, Mayo Clinic, Phoenix, AZ, Dana-Farber Cancer Institute, Palm Beach, FL, Dana-Farber Cancer Institute, Boston, MA, H. Lee Moffitt Cancer Center, Tampa, FL, City of Hope Comprehensive Cancer Center, Duarte, CA, The University of Utah Huntsman Cancer Institute, Salt Lake City, UT, Cleveland Clinic Taussig Cancer Center, Cleveland, OH, City of Hope Comprehensive Cancer Center, Durante, CA, Mayo Clinic, Rochester, MN, Stanford University School of Medicine, Stanford, CA

Research Funding

No funding received
None.

Background: Cilta-cel was FDA approved in 2022 for the treatment of RRMM. We evaluated the outcomes of patients treated with intended SOC cilta-cel. Methods: 12 US academic medical centers contributed data to this retrospective study. As of 12/31/2022, 177 patients were leukapheresed and 139 received cilta-cel. Results: The table describes the study population compared to the CARTITUDE-1 trial. More patients in our study had extramedullary disease (EMD, 35%) and high-risk cytogenetics (41%). 55% of the patients would not have met eligibility criteria for CARTITUDE-1. Common reasons for ineligibility were cytopenias (19%), prior BCMA therapy (14%), organ dysfunction (12%), oligosecretory disease (13%), and plasma cell leukemia (8%). 83% of the patients received bridging chemotherapy (overall response rate, ORR: 28%). Lymphodepletion included fludarabine (Flu) + cyclophosphamide (Cy): 81%, bendamustine: 11%, Cy: 4%, and cladribine + Cy: 4%. Median CAR-T cells infused were 0.6 million/kg (range: 0.1-0.9), and 19% of patients were treated on an expanded access protocol (EAP). Median follow-up was 2.3 months (range: 0-8). Cytokine release syndrome (CRS) was seen in 81% (≥ grade 3: 7%) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 22% (≥ grade 3: 8%) of patients. Tocilizumab, steroids, and anakinra were used in 61%, 44%, and 10% of patients, respectively. Delayed neurotoxicity (NT) was seen in 9% (cranial nerve palsy: 8, Parkinsonism: 2, others: 3). Grade ≥ 3 cytopenias at day ≥ 30 were seen in 75% of patients. Infections were seen in 32% of patients. Day 30 (N=115) and best response rates (N=118) were: ≥ partial response (PR), 75/80%; ≥ very good PR, 44/62%; and ≥ complete response (CR), 26/40%, respectively. In the non-EAP FluCy population (N=88), best ORR/≥CR were 89/49%. 17 patients died by data cut-off, 4 due to disease progression and 13 (9%) due to non-relapse mortality (NRM) (grade 5 CRS: 3, infection: 6, CRS/infection: 1, grade 5 ICANS: 1, delayed NT: 2). Conclusions: Patients treated with intended SOC cilta-cel had a favorable ORR (80%) despite a larger proportion of patients having high-risk features relative to trial patients and limited follow-up. Response rates were higher in patients receiving conforming products with FluCy conditioning (89%). Delayed NT and NRM were seen in 9% of patients. Results will be updated with continued follow-up. D.K.H., K.K.P, M.J., Y.L. & S.S. contributed equally.

Comparison of patient characteristics and outcomes by intended SOC vs. CARTITUDE-1 trial participants.

Intended SOC, N=139CARTITUDE-1, N=97
Median age, yrs6461
ECOG PS 0 or 191%96%
Extramedullary disease35%13%
High-risk cytogenetics41%24%
Median prior regimens6 (2-18)6 (4-8)
Penta-refractory disease36%42%
Grade ≥ 3 CRS and ICANS7%, 8%4%, 2%
Delayed NT/Parkinsonism9%/1.4%12%/6%
Best ORR/≥CRAll: 80%/40%
Non-EAP FluCy: 89%/49%
98%/83%

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Hematologic Malignancies—Plasma Cell Dyscrasia

Track

Hematologic Malignancies

Sub Track

Cell Therapy, Bispecific Antibodies, and Autologous Stem Cell Transplantation for Plasma Cell Disorders

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 8012)

DOI

10.1200/JCO.2023.41.16_suppl.8012

Abstract #

8012

Poster Bd #

4

Abstract Disclosures