IDECABTAGENE VICLEUCEL (IDE-CEL; BB2121), A BCMA-TARGETED CAR T CELL THERAPY, IN PATIENTS WITH RELAPSED AND REFRACTORY MULTIPLE MYELOMA: INITIAL KARMMA RESULTS
Author(s): ,
Jesus San Miguel
Affiliations:
Clinical Universidad de Navarra,Navarra,Spain
,
Nina Shah
Affiliations:
University of California San Francisco,San Francisco,United States
,
Albert Oriol
Affiliations:
Institut Català d'Oncologia and Josep Carreras Institute, Hospital Germans Trias i Pujol,Badalona,Spain
,
Philippe Moreau
Affiliations:
Centre Hospitalier Universitaire de Nantes,Nantes,France
,
Ibrahim Yakoub-Agha
Affiliations:
Univ Lille, Inserm, CHU Lille, INSERM, Infinite, U1286,Lille,France
,
Michel Delforge
Affiliations:
University Hospital Leuven,Leuven,Belgium
,
Deepu Madduri
Affiliations:
Mount Sinai Hospital,New York,United States
,
Ankit Kansagra
Affiliations:
UT Southwestern Medical Center,Dallas,United States
,
Hermann Einsele
Affiliations:
University Hospital Würzburg,Würzburg,Germany
,
Hartmut Goldschmidt
Affiliations:
University Hospital Heidelberg,Heidelberg,Germany
,
Katja Weisel
Affiliations:
University Medical Center of Hamburg-Eppendorf,Hamburg,Germany
,
Michele Cavo
Affiliations:
Bologna University School of Medicine,Bologna ,Italy
,
Donna Reece
Affiliations:
Princess Margaret Cancer Centre,Toronto,Canada
,
Alessandro Rambaldi
Affiliations:
University of Milan and ASST Papa Giovanni XXIII,Bergamo,Italy
,
Paula Rodríguez-Otero
Affiliations:
Clinical Universidad de Navarra,Navarra,Spain
,
Fabio Petrocca
Affiliations:
Boston University School of Medicine,Boston,United States
,
Jamie Connarn
Affiliations:
Bristol-Myers Squibb,Summit,United States
,
Julie Wang
Affiliations:
Bristol-Myers Squibb,Summit,United States
,
Liping Huang
Affiliations:
Bristol-Myers Squibb,Summit,United States
,
Timothy B. Campbell
Affiliations:
Bristol-Myers Squibb,Summit,United States
,
Kristen Hege
Affiliations:
Bristol-Myers Squibb,San Francisco,United States
Nikhil Munshi
Affiliations:
The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School,Boston,United States
EHA Library. San Miguel J. 06/12/20; 295029; S209
Jesus San Miguel
Jesus San Miguel
Contributions
Abstract

Abstract: S209

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Management of relapsed/refractory multiple myeloma and minimal residual disease assessment

Background
Triple-class exposed patients (pts) with relapsed and refractory multiple myeloma (RRMM) who progress on immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies (mAbs) have poor outcomes. In the phase I CRB-401 study, idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T cell therapy, showed promising tolerability and efficacy in relapsed or refractory multiple myeloma pts with ≥3 prior lines of therapy including an IMiD and a PI, or who were refractory to both drug classes (N Engl J Med. 2019;380:1726-1737).

Aims
To report primary efficacy and safety data from the pivotal phase II KarMMa trial of ide-cel in RRMM (NCT03361748).

Methods
Enrolled pts had ≥3 prior regimens (including an IMiD, a PI, and an anti-CD38 mAb) and were refractory to their last regimen per IMWG criteria. After lymphodepletion with cyclophosphamide 300 mg/m2 plus fludarabine 30 mg/m2 x 3 d, pts received 150─450 × 10CAR+ T cells (target dose levels). The primary endpoint was overall response rate (ORR). Secondary endpoints included complete response (CR) rate, duration of response (DOR), and progression-free survival (PFS).

Results
Of 140 pts enrolled in KarMMa, 128 received ide-cel infusion. The median age was 61 y, and the median number of prior regimens was 6 (range, 3-16); 84% were triple- and 26% were penta-refractory. Most pts (88%) received bridging therapy prior to lymphodepletion. With a median follow-up duration of 11.3 mo at the data cutoff for the primary analyses (16 October 2019), 70 pts (55%) were still ongoing in the primary study and 5 (4%) had entered a long-term follow-up study. The most common reason for discontinuation was death or pt withdrawal after disease progression (n=55). Clinically meaningful efficacy was observed at each of the 3 target doses explored and generally increased with dose (Table). ORR was 73% across all dose levels and 81% in pts who received 450 × 106 CAR+ T cells. Across doses, the CR rate was 31%, median time to response was 1.0 mo (range, 0.5-8.8), and median DOR was 10.6 mo (95% CI, 9.0-11.3). With a median follow-up duration of 10.2 mo, median PFS was 8.6 mo (95% CI, 5.6-11.3) for the overall pt population and 11.3 mo (95% CI, 8.8-12.4) for the 54 pts who received 450 × 106 CAR+ T cells. Response rates were consistent (ORR ≥50%) in most subgroups examined, including older and historically difficult-to-treat pts (penta-refractory, high tumor burden, extramedullary disease, etc). The most common adverse events (AEs) of special interest were cytopenias (97%), cytokine release syndrome (CRS; 84%), and infections (69%). CRS was mostly grade 1/2; 5 pts (4%) had grade 3, 1 had grade 4, and 1 had grade 5 (at 300 × 106). Neurotoxicity developed in 23 pts (18%); 4 pts (3%) had grade 3 and none had grade ≥4. Four grade 5 ide-cel−related AEs occurred (bronchopulmonary aspergillosis, pneumonia cytomegaloviral, gastrointestinal hemorrhage, and CRS). Median peak CAR+ T cell expansion occurred at 11 d. Expansion was higher in responders, and expansion parameters (AUC0−28d, Cmax) increased with higher dose, with substantial exposure overlap across doses. Durable persistence was observed, with CAR+ T cells detected in 29 of 49 (59%) and 4 of 11 pts (36%) at 6 and 12 mo postinfusion, respectively. 

Conclusion
In the KarMMa trial, ide-cel demonstrated deep, durable responses in heavily pretreated RRMM pts. Efficacy and safety results reflected prior reports and support a favorable clinical benefit-risk profile of ide-cel across the target dose levels.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): CAR-T, Myeloma, Refractory, Relapse

Abstract: S209

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Management of relapsed/refractory multiple myeloma and minimal residual disease assessment

Background
Triple-class exposed patients (pts) with relapsed and refractory multiple myeloma (RRMM) who progress on immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies (mAbs) have poor outcomes. In the phase I CRB-401 study, idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T cell therapy, showed promising tolerability and efficacy in relapsed or refractory multiple myeloma pts with ≥3 prior lines of therapy including an IMiD and a PI, or who were refractory to both drug classes (N Engl J Med. 2019;380:1726-1737).

Aims
To report primary efficacy and safety data from the pivotal phase II KarMMa trial of ide-cel in RRMM (NCT03361748).

Methods
Enrolled pts had ≥3 prior regimens (including an IMiD, a PI, and an anti-CD38 mAb) and were refractory to their last regimen per IMWG criteria. After lymphodepletion with cyclophosphamide 300 mg/m2 plus fludarabine 30 mg/m2 x 3 d, pts received 150─450 × 10CAR+ T cells (target dose levels). The primary endpoint was overall response rate (ORR). Secondary endpoints included complete response (CR) rate, duration of response (DOR), and progression-free survival (PFS).

Results
Of 140 pts enrolled in KarMMa, 128 received ide-cel infusion. The median age was 61 y, and the median number of prior regimens was 6 (range, 3-16); 84% were triple- and 26% were penta-refractory. Most pts (88%) received bridging therapy prior to lymphodepletion. With a median follow-up duration of 11.3 mo at the data cutoff for the primary analyses (16 October 2019), 70 pts (55%) were still ongoing in the primary study and 5 (4%) had entered a long-term follow-up study. The most common reason for discontinuation was death or pt withdrawal after disease progression (n=55). Clinically meaningful efficacy was observed at each of the 3 target doses explored and generally increased with dose (Table). ORR was 73% across all dose levels and 81% in pts who received 450 × 106 CAR+ T cells. Across doses, the CR rate was 31%, median time to response was 1.0 mo (range, 0.5-8.8), and median DOR was 10.6 mo (95% CI, 9.0-11.3). With a median follow-up duration of 10.2 mo, median PFS was 8.6 mo (95% CI, 5.6-11.3) for the overall pt population and 11.3 mo (95% CI, 8.8-12.4) for the 54 pts who received 450 × 106 CAR+ T cells. Response rates were consistent (ORR ≥50%) in most subgroups examined, including older and historically difficult-to-treat pts (penta-refractory, high tumor burden, extramedullary disease, etc). The most common adverse events (AEs) of special interest were cytopenias (97%), cytokine release syndrome (CRS; 84%), and infections (69%). CRS was mostly grade 1/2; 5 pts (4%) had grade 3, 1 had grade 4, and 1 had grade 5 (at 300 × 106). Neurotoxicity developed in 23 pts (18%); 4 pts (3%) had grade 3 and none had grade ≥4. Four grade 5 ide-cel−related AEs occurred (bronchopulmonary aspergillosis, pneumonia cytomegaloviral, gastrointestinal hemorrhage, and CRS). Median peak CAR+ T cell expansion occurred at 11 d. Expansion was higher in responders, and expansion parameters (AUC0−28d, Cmax) increased with higher dose, with substantial exposure overlap across doses. Durable persistence was observed, with CAR+ T cells detected in 29 of 49 (59%) and 4 of 11 pts (36%) at 6 and 12 mo postinfusion, respectively. 

Conclusion
In the KarMMa trial, ide-cel demonstrated deep, durable responses in heavily pretreated RRMM pts. Efficacy and safety results reflected prior reports and support a favorable clinical benefit-risk profile of ide-cel across the target dose levels.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): CAR-T, Myeloma, Refractory, Relapse

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