-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

2411b Real-World Efficacy Outcomes of Ciltacabtagene Autoleucel in Relapsed Refractory Multiple Myeloma: A Comparative Study with the Cartitude-1 Trial

Program: Oral and Poster Abstracts
Session: 907. Outcomes Research: Plasma Cell Disorders: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Practice (Health Services and Quality), Clinical Research, Health outcomes research, Real-world evidence
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Ishita Kamboj1,2*, Darryl Chang, MD3, Alma Habib, MD4, Andrew Vegel, MD5*, Emily Struble, DNP5*, Hira Shaikh, MD2,5*, Christopher Strouse, MD2,5, James A Davis, PharmD2,6*, Aliya Rashid, DO, MPH2,7,8, Kevin Graf, MD2,9*, Kimberly M Green, DO10*, Muhammad Umair Mushtaq, MD2,8, Zahra Mahmoudjafari, PharmD2,8*, Hamza Sloan Hashmi, MD11,12,13*, Joseph P. McGuirk, DO8, Al-Ola Abdallah, MD2,8, Shebli Atrash, MD2,14, Abdullah Mohammad Khan, MD, MBBS2,4 and Nausheen Ahmed, MD2,15

1Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, KANSAS CITY, MO
2US Myeloma Innovations Research Collaborative (USMIRC), Kansas City, KS
3Levine Cancer Institute, Atrium Health Wake Forest University School of Medicine, Charlotte, NC
4Division of Hematology, The Ohio State University, Columbus, OH
5Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa Hospitals and Clinics, Iowa City, IA
6Department of Hematology-Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC
7Internal Medicine, University of Kansas Medical Center, Kansas City, KS
8Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS
9Department of Hematology-Oncology, Medical University of South Carolina, Charleston, SC
10Division of Hematology-Oncology, Medical University of South Carolina, Charleston, SC
11Myeloma Service, Department of Medicine, Memorial Sloan Kettering, New York, NY
12Department of Hematology-Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, NY
13US Myeloma Innovations Research Collaborative (USMIRC), Kansas City, NY
14Department of Hematologic Oncology & Blood Disorders, Levine Cancer Institute, Atrium Health Wake Forest University School of Medicine, Charlotte, NC
15University of Kansas Cancer Center, Kansas City, KS

Introduction:

The CARTITUDE-1 (C-1) trial, a Phase Ib/II global single-arm pivotal trial, resulted in the approval of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T cell therapy, in 2022 for patients with relapsed refractory multiple myeloma (RRMM) who had progressed after at least 4 lines of therapy. The inclusion criteria for C-1 may not fully represent the real-world (RW) patient (pt) population. This study highlights a RW cohort of pts who may not have met the C-1 trial's eligibility criteria, to evaluate the effectiveness of cilta-cel in RRMM and compare the outcomes with those of the C-1 trial.

Method:

This multi-center retrospective study from 5 centers included 73 RW pts who had received cilta-cel. The International Myeloma Working Group (IMWG) criteria was used to assess the responses. ORR was defined as at least ≥ PR as best response. Baseline characteristics, ORR, DOR, progression-free survival (PFS), and overall survival (OS) were evaluated and compared to the C-1 population to identify any statistically significant differences. Individual pt data was estimated from the C1 publication (Martin T et al. J Clin Oncol. doi:10.1200/JCO.22.00842) and compared with RW using the Kaplan-Meier method with a regression model for survival analysis. Group comparisons were performed using the Wilcoxon rank sum test and Pearson’s Chi-squared test.

Results:

In the RW cohort, there were 73 pts, while there were 97 pts in C-1. The median age in the RW cohort was 65.5 years, with the majority being white (78%) and male (52%). Thirty-three percent of patients had R-ISS III, 29% had extramedullary disease (EMD), 15% had del 17p, 6.8% had t (4;14) and 2.7% had t (14:16). The majority of patients were refractory to lenalidomide (74%), pomalidomide (74%), carfilzomib (63%), anti-CD38 monoclonal antibody (88%). Additionally, 47% of patients were refractory to bortezomib, and 14% had prior BCMA exposure. The median LOT was 5 (4-12), and 79% had prior stem cell transplants.

RW baseline demographics, such as age, ethnic minorities, gender, prior therapies, disease characteristics including high-risk cytogenetics were broadly similar compared to the C-1 population. Notably, in the RW cohort, fewer patients had ECOG 0 (16% vs 40%, p=0.0006), and more patients had EMD compared to C-1 (29% vs 13%, p = 0.02). Furthermore, fewer RW pts were refractory to bortezomib (47% vs 68% p=0.007) and anti-CD38 monoclonal antibody (88% vs 97%, p = 0.03).

In the RW cohort, 37% of patients did not meet the inclusion criteria for C-1. Reasons for not meeting C-1 inclusion criteria were as follows: ejection fraction (EF) < 45% (n=1, 1.4%), Creatinine clearance < 45ml/min (n=4, 5.5%), and fewer than three lines of therapy (n=11,15%). Nine pts9 (13.5%) patients had ECOG ≥2. Additionally, 10 (14%) patients had previous BCMA exposure, 1 (1.4%) patient had co-existing plasma cell leukemia, and 1 (1.4%) patient had co-existing amyloidosis.

The median follow-up for the real-world (RW) cohort was 11.67 months (4.9 -16.6). Rates of stringent complete responses (sCR) were lower in RW compared to C-1 cohort (30% vs 67%, p<0.0001), while complete response (CR) rates were higher (30% vs 0%, p<0.001). Partial response (PR) was higher (14% vs 4%, p=0.034) while very good partial response (VGPR) was similar in RW (14% vs 26%, p=0.1). Best response as ≥VGPR was lower in the RW cohort compared to C-1 (74% vs 93%, p<0.0001). Disease progression as best response was higher in RW (7.8% vs 1%, p=0.038), and the ORR in RW was lower (88% vs 97%, p=0.015)

The 2-year PFS and OS for the RW cohort compared to the 2-year outcomes in C-1 were similar (PFS: 58% in RW vs 62% in C-1, p=0.98, and OS: 72% vs 74%, p=0.9).

Conclusions:

A significant proportion of RW patients did not meet the criteria for enrollment in the C-1 trial. Although the overall response rate was lower in the real-world setting, the progression-free survival and overall survival outcomes were similar, indicating comparable efficacy. These findings suggest that despite a higher percentage of patients with more significant comorbidities, lower performance status, and more advanced disease in the real-world compared to the C-1 trial, cilta-cel in real world setting demonstrates similar effectiveness to CARTITUDE-1 in the treatment of relapsed or refractory multiple myeloma.

Disclosures: Strouse: Janssen: Research Funding; Seagen: Research Funding; Poseida: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squibb: Research Funding. Davis: Janssen Biotech: Speakers Bureau. Mahmoudjafari: Janssen: Consultancy; Sanofi: Consultancy. McGuirk: Sana technologies: Consultancy; Legend biotech: Consultancy; CRISPR therapeutics: Consultancy; NEKTAR therapeutics: Consultancy; Caribou bio: Consultancy; Autolus: Consultancy; Envision: Consultancy; Allo Vir: Consultancy; Novartis: Consultancy; Kite: Consultancy; BMS: Consultancy. Atrash: Janssen: Honoraria; Karyopharm: Research Funding; Amgen: Research Funding; GSK: Research Funding. Khan: Amgen: Speakers Bureau; Sanofi: Research Funding, Speakers Bureau; BMS: Research Funding, Speakers Bureau. Ahmed: Kite/Gilead: Consultancy, Honoraria; Legend Biotech: Consultancy, Honoraria; BMS: Consultancy, Honoraria.

*signifies non-member of ASH