Meeting
2021 ASCO Annual Meeting
Characteristics of neurotoxicity associated with idecabtagene vicleucel (ide-cel, bb2121) in patients with relapsed and refractory multiple myeloma (RRMM) in the pivotal phase II KarMMa study.
Authors
Salomon Manier
Centre Hospitalier Regional Universitaire de Lille, Lille, France
Salomon Manier , Ankit J. Kansagra , Larry D. Anderson, Jr , Jesus G. Berdeja , Sundar Jagannath , Yi Lin , Sagar Lonial , Nina Shah , Noopur S. Raje , David Samuel DiCapua Siegel , Albert Oriol , Anna Truppel-Hartmann , Everton Rowe , Payal Patel , Amit Agarwal , Timothy B. Campbell , Paula Rodríguez-Otero , Nikhil C. Munshi
Organizations
Centre Hospitalier Regional Universitaire de Lille, Lille, France, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN, Mount Sinai Medical Center, New York, NY, Division of Hematology, Mayo Clinic, Rochester, MN, Emory School of Medicine, Atlanta, GA, University of California San Francisco, San Francisco, CA, Massachusetts General Hospital, Boston, MA, Hackensack University Medical Center, Hackensack, NJ, Institut Josep Carreras and Institut Catala d’Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain, BlueBird Bio, Cambridge, MA, Bristol Myers Squibb, Princeton, NJ, Clinica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra, Navarra, Spain, The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
Research Funding
Pharmaceutical/Biotech Company
Celgene, a Bristol-Myers Squibb Company, and bluebird bio
Background: Ide-cel, a BCMA-directed CAR T cell therapy, showed promising efficacy in patients (pts) with RRMM in the KarMMa study with an ORR of 73% and a CRR of 33% across target doses of 150–450 × 106 CAR+ T cells (Munshi NC, et al. J ClinOncol 2020;38[suppl 15]. Abstract 8503). Associations of neurotoxicity (NT) with pt and disease characteristics, pt management, and impact on outcomes in the KarMMa study are reported here. Methods: Enrolled pts were triple-class exposed and refractory to their last regimen, with ide-cel given at target doses of 150, 300, or 450 × 106 CAR+ T cells after lymphodepletion (NCT03361748). Investigator-identified NT events were captured under the single preferred term of neurotoxicity and graded according to NCI CTCAE v4.03. Events were managed with corticosteroids (CS), anakinra (ANR), and tocilizumab (Toci) as needed. Results: Of 128 pts treated with ide-cel, NT was reported in 23 (18%); 12 pts (9%) had maximum grade (gr) 1 NT, 7 (5%) had gr 2, and 4 (3%) had gr 3. No gr 4 or 5 NT occurred. Most baseline characteristics were similar in pts with and without NT, including stage III disease (22% and 15%), high-risk cytogenetics (39% and 34%), and extramedullary disease (35% and 40%); exceptions were high tumor burden (65% and 48%) and sex (48% and 62% men). NT (any gr/gr 3) occurred in 0%/0%, 17%/1%, and 20%/6% of pts at doses of 150, 300, and 450 × 106 CAR+ T cells. Median time to onset was similar regardless of gr, and there were no late-onset events (Table). NT was managed with CS in 10 pts (43%), Toci in 3 (13%), and ANR in 1 (4%). Median (range) time to first use of CS was 2 d (1–6). ORR and DOR were similar in pts with and without NT (Table). All NT occurred in the proximity of cytokine release syndrome (CRS) events with the start date of NT events either overlapping with or occurring within 1 wk of the start of a CRS event. Conclusions: NT occurred early in the KarMMa study, was generally of short duration, and was mostly gr 1/2 with no gr ≥4 events. All NT was proximal to CRS. Pts with NT had a favorable ORR after ide-cel treatment. These results continue to demonstrate the durable efficacy and tolerability of ide-cel in pts with RRMM. Clinical trial information: NCT03361748
| NT events | Gr 1 (n = 12) | Gr 2 (n = 7) | Gr 3 (n = 4) | Any gr (n = 23) |
|---|---|---|---|---|
| Time to onset, median (range), d | 2 (1–10) | 2 (1–4) | 3 (1–4) | 2 (1–10) |
| No. of events | 13 | 7 | 4 | 24 |
| Duration/event, % 1–5 d 6–10 d >10 d Ongoing Median (range), da | 69 31 0 0 3 (1–9) | 43 29 14 14 6 (1–26) | 25 0 75 0 14 (2–22) | 54 25 17 4 3 (1–26) |
| CS / Toci / ANR, % | 17 / 8 / 0 | 57 / 0 / 0 | 100 / 50 / 25 | 43 / 13 / 4 |
| Efficacy | No NT (n = 105) | NT, any gr (n = 23) | ||
| Response, % (95% CI) ORR CRR | 73 (64.9−81.8) 35 (26.1−44.4) | 74 (56.0−91.9) 22 (4.9−38.6) | ||
| PFS, median (95% CI), mo | 8.9 (5.7−11.9) | 6.1 (3.0−11.1) | ||
| DOR,b median (95% CI), mo | 11.0 (8.0−11.3) | 10.0 (4.0−NE) | ||
| OS, median (95% CI), mo | 19.4 (18.0−NE) | NE (12.3−NE) | ||
Data cutoff: 14 Jan 2020. NE, not estimable. aOngoing NT excluded. bAmong responders.
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Abstract Details
Session Type
Poster Session
Session Title
Hematologic Malignancies—Plasma Cell Dyscrasia
Track
Hematologic Malignancies
Sub Track
Multiple Myeloma
Clinical Trial Registration Number
NCT03361748
Citation
J Clin Oncol 39, 2021 (suppl 15; abstr 8036)
DOI
10.1200/JCO.2021.39.15_suppl.8036
Abstract #
8036
Poster Bd #
Online Only
Abstract Disclosures
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