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Comparative Study
. 2024 May 31;14(1):88.
doi: 10.1038/s41408-024-01043-5.

Comparison of infectious complications with BCMA-directed therapies in multiple myeloma

Karthik Nath #  1 , Tala Shekarkhand #  2 , David Nemirovsky  3 , Andriy Derkach  3 , Bruno Almeida Costa  4   5 , Noriko Nishimura  2   6 , Tasmin Farzana  1 , Colin Rueda  2 , David J Chung  1   6   7 , Heather J Landau  1   6   7 , Oscar B Lahoud  1   6   7 , Michael Scordo  1   6   7 , Gunjan L Shah  1   6   7 , Hani Hassoun  2   7 , Kylee Maclachlan  2   7 , Neha Korde  2   7 , Urvi A Shah  2   7 , Carlyn Rose Tan  2   7 , Malin Hultcrantz  2   7 , Sergio A Giralt  1   6   7 , Saad Z Usmani  1   2   6   7 , Zainab Shahid  7   8 , Sham Mailankody  9   10   11 , Alexander M Lesokhin  12   13   14
Affiliations
Comparative Study

Comparison of infectious complications with BCMA-directed therapies in multiple myeloma

Karthik Nath et al. Blood Cancer J. .

Abstract

B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25-0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31-3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05-3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21-0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17-0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients.

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Conflict of interest statement

TS reports honoraria from Genentech; DJC receives research funding from Genentech; HJL has served as a paid consultant for Takeda, Genzyme, Janssen, Karyopharm, Pfizer, Celgene, Caelum Biosciences, and has received research support from Takeda; OBL reports serving on Advisory Board for MorphoSys Inc., Kite, Daiichi Sankyo Inc., Incyte; Consulting for: Incyte; MS served as a paid consultant for McKinsey & Company, Angiocrine Bioscience, Inc., and Omeros Corporation; received research funding from Angiocrine Bioscience, Inc., Omeros Corporation, and Amgen, Inc.; served on ad hoc advisory boards for Kite – A Gilead Company; and received honoraria from i3Health, Medscape, and CancerNetwork for CME-related activity; GS reports research funding from Janssen, Amgen, BMS, Beyond Spring, and serves on the Data Safety Monitoring Board for ArcellX. GS research funding to the institution from Janssen, Amgen, BMS, Beyond Spring, and GPCR, and on DSMB for ArcellX; HH reports grants from Celgene, Takeda, and Janssen, outside the submitted work; NK reports research funding through Amgen and participates in advisory board with Medimmune; US reports personal fees from Physicians Educations Resources; grants and other from Celgene/Bristol Myers Squibb; other from Janssen; and grants from Parker Institute for Cancer Immunotherapy and Myeloma Crowd, outside the submitted work; CT: reports research funding from Janssen and personal fees from Physician Educations Resource; MH: reports research funding from Amgen, Daiichi Sankyo, GlaxoSmithKline; has received honoraria for consultancy/participated in advisory boards for Curio Science LLC, Intellisphere LLC, Bristol Myer Squibb, and GlaxoSmithKline; SAG reports personal fees from and an advisory role (scientific advisory board) in Actinium, Celgene, Bristol Myers Squibb, Sanofi, Amgen, Pfizer, GlaxoSmithKline, JAZZ, Janssen, Omeros, Takeda, and Kite, outside the submitted work; SZU reports grants and personal fees from AbbVie, 404 Amgen, BMS, Celgene, GSK, Janssen, Merck, MundiPharma, Oncopeptides, 405 Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, and Takeda; SM received consulting fees from Evicore, Optum, BioAscend, Janssen Oncology, Bristol Myers Squibb, AbbVie, ECor1, Galapagos, and Legend Biotech. Memorial Sloan Kettering Cancer Center receives research funding from the NCI, Janssen Oncology, Bristol Myers Squibb, Allogene Therapeutics, Fate Therapeutics, and Takeda Oncology for research led by Sham Mailankody. Sham Mailankody received honoraria from OncLive, Physician Education Resource, MJH Life Sciences, and Plexus Communications; AML reports grants from Bristol Myers Squibb; personal fees from Trillium Therapeutics; grants, personal fees and non-financial support from Pfizer; and grants and personal fees from Janssen and Arcellx, outside the submitted work. AML also has a patent US20150037346A1 with royalties paid.

Figures

Fig. 1
Fig. 1
Estimated cumulative incidence of grade ≥3 infections over time.
Fig. 2
Fig. 2. Functional serum IgG levels over time after treatment initiation up to 6 months of follow up.
The x-axis represents individual patients. The colored bars report the number of days within the 1st 6-months during which each patient experienced functional hypogammaglobulinemia (IgG < 400 mg/dL) or non-hypogammaglobulinemia (IgG ≥ 400 mg/dL).
Fig. 3
Fig. 3. Absolute neutrophil count over time after treatment initiation up to 6 months of follow up.
The x-axis represents individual patients. The colored bars report the number of days within the 1st 6-months during which each patient experienced neutropenia (neutrophil count <1000/mcL) or non-neutropenia (neutrophil count ≥1000/mcL).
See this image and copyright information in PMC

Update of

References

    1. Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, et al. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood. 2004;103:689–94. doi: 10.1182/blood-2003-06-2043. - DOI - PubMed
    1. Nath K, Mailankody S, Usmani SZ. The role of chimeric antigen receptor T-Cell therapy in the era of bispecific antibodies. Hematol/Oncol Clin. 2023;37:1201–14. doi: 10.1016/j.hoc.2023.05.011. - DOI - PMC - PubMed
    1. Martin T, Usmani SZ, Berdeja JG, Agha M, Cohen AD, Hari P, et al. Ciltacabtagene autoleucel, an anti–B-cell maturation antigen chimeric antigen receptor T-Cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up. J Clin Oncol. 2022;41:JCO.22.00842. - PMC - PubMed
    1. Munshi NC, Anderson LD, Shah N, Madduri D, Berdeja J, Lonial S, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N. Engl J Med. 2021;384:705–16. doi: 10.1056/NEJMoa2024850. - DOI - PubMed
    1. Moreau P, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387:495–505. doi: 10.1056/NEJMoa2203478. - DOI - PMC - PubMed

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