Adjusted Comparison of Outcomes between Patients from CARTITUDE-1 versus Multiple Myeloma Patients with Prior Exposure to PI, Imid and Anti-CD-38 from a German Registry
by
, , ,
Maximilian Merz
1,*, 
Hartmut Goldschmidt
2,
Parameswaran Hari
3,
Mounzer Agha
4,
Joris Diels
5,
Francesca Ghilotti
6,
Nolen J. Perualila
5,
Jedelyn Cabrieto
5,
Benjamin Haefliger
7,
Henrik Sliwka
8,
Jordan M. Schecter
9,
Carolyn C. Jackson
9,
Yunsi Olyslager
5,
Muhammad Akram
10,
Tonia Nesheiwat
10,
Lenka Kellermann
11 and
Sundar Jagannath
12 1
Cell Therapy and Hemostaseology, Department of Hematology, University Hospital of Leipzig, 04103 Leipzig, Germany
2
Internal Medicine V and National Center for Tumor Diseases, University Clinic Heidelberg, 69120 Heidelberg, Germany
3
Medical College of Wisconsin, Milwaukee, WI 53226, USA
4
School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
5
Janssen Pharmaceutica NV, 2340 Beerse, Belgium
6
Janssen-Cilag SpA, 20093 Cologno Monzese, Italy
7
Cilag GmbH International, 6300 Zug, Switzerland
8
Janssen-Cilag Pharma GmbH, 1020 Vienna, Austria
9
Janssen R&D, Raritan, NJ 08869, USA
10
Legend Biotech USA, Inc., Piscataway, NJ 08854, USA
11
Oncology Information Service (O.I.S), 79098 Freiburg, Germany
12
Mount Sinai Medical Center, New York, NY 10029, USA
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(23), 5996; https://doi.org/10.3390/cancers13235996
Submission received: 20 September 2021
/
Revised: 12 November 2021
/
Accepted: 22 November 2021
/
Published: 29 November 2021
(This article belongs to the Collection Advances in Multiple Myeloma Research and Treatment)
Simple Summary
There is an urgent need to develop new treatments for patients with relapsed/refractory multiple myeloma (RRMM) to address unmet medical needs. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel approach with the potential for long-term disease control. Ciltacabtagene autoleucel (cilta-cel) is a CAR-T treatment studied in patients with RRMM in the CARTITUDE-1 clinical trial and has shown clinically important effects. However, CARTITUDE-1 was a single arm study. The current study compared outcomes for cilta-cel with an external cohort of German patients that are similar to the ones in CARTITUDE-1 to compare the effectiveness of cilta-cel versus established clinical practice. To overcome potential bias, individual patient data were used to adjust for the differences in patient characteristics between cohorts. The results showed substantially better outcomes for cilta-cel on both overall survival and the time to next treatment. These findings highlight cilta-cel’s potential as a novel, effective treatment to address unmet treatment needs.
Abstract
Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the comparisons between both cohorts, using the inverse probability of treatment weighting (IPW; average treatment effect in the treated population (ATT) and overlap population (ATO) weights) and multivariable Cox proportional hazards regression. Outcomes were compared in intention-to-treat (HR, IPW-ATT: TTNT: 0.13 (95% CI: 0.07, 0.24); OS: 0.14 (95% CI: 0.07, 0.25); IPW-ATO: TTNT: 0.24 (95% CI: 0.12, 0.49); OS: 0.26 (95% CI: 0.13, 0.54)) and modified intention-to-treat (HR, IPW-ATT: TTNT: 0.24 (95% CI: 0.09, 0.67); OS: 0.26 (95% CI: 0.08, 0.84); IPW-ATO: TTNT: 0.26 (95% CI: 0.11, 0.59); OS: 0.31 (95% CI: 0.12, 0.79)) populations. All the comparisons were statistically significant in favor of cilta-cel. These results highlight cilta-cel’s potential as a novel, effective treatment to address unmet needs in patients with RRMM.
