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Review
. 2025 May 1;17(1):e2025045.
doi: 10.4084/MJHID.2025.045. eCollection 2025.

Bispecific Antibodies and CAR T in Multiple Myeloma: Appropriate Selection of Patients and Sequencing

M Puppi #  1   2 , I Sacchetti #  1   2 , K Mancuso  1   2 , P Tacchetti  1 , L Pantani  1 , I Rizzello  1   2 , M Iezza  1   2 , M Talarico  1   2 , E Manzato  1   2 , S Masci  1   2 , R Restuccia  1   2 , S Barbato  1   2 , S Armuzzi  1   2 , B Taurisano  1   2 , I Vigliotta  1 , E Zamagni  1   2
Affiliations
Review

Bispecific Antibodies and CAR T in Multiple Myeloma: Appropriate Selection of Patients and Sequencing

M Puppi et al. Mediterr J Hematol Infect Dis. .

Abstract

T-cell redirecting therapies (TCR) marked a step forward in the treatment of relapsed/refractory multiple myeloma (RRMM). These agents, represented by chimeric antigen receptor (CAR) T-cells and bispecific antibodies (BsAbs), proved to ameliorate the prognosis of difficult-to-treat patients in pivotal clinical trials, leading to their introduction into clinical practice. Both strategies rely on recruiting patients' T-cells against specific tumor antigens, with B-cell maturation antigen (BCMA) and G-protein coupled receptor group C family 5 member D (GPRC5D) being the targets most extensively studied. Nevertheless, most of these regimens under the current label do not hesitate in a clear plateau of survival curves, thus raising the scenario of patients receiving more than one TCR agent in sequence. Also, they differ in their toxicity profiles and administration features. Consequently, the appropriate application of these agents mandates a careful selection of the right treatment for the right patient, with the ultimate intent of optimizing patient outcomes. In this respect, practical considerations regarding tumor- and patient-specific features are of high importance. Tailored clinical trials and analysis of real-word experiences are also crucial to produce evidence-based recommendations. Likewise, pre-clinical research is critical for the conceptualization of treatment algorithms potentially driven by immunological clues and knowledge of mechanisms of resistance. In this review we aim at providing practical guidance for defining the most appropriate treatment sequencing and determining the selection of patients for each treatment.

Keywords: Bispecific Antibodies; CAR-T; Multiple Myeloma; Patient selection; T-cell redirecting therapies; Treatment sequencing.

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Conflict of interest statement

Competing interests: KM received honoraria from Celgene, Takeda, Amgen, Sanofi, Janssen, GSK, Pfizer, Menarini-Stemline; PT has received honoraria from Amgen, Bristol-Myers Squibb/Celgene, Janssen, Takeda, AbbVie, Sanofi, GlaxoSmithKline, Pfizer and Menarini-Stemline; LP has received honoraria from GlaxoSmithKline and Sanofi; IR has served in advisory role for GlaxoSmithKline and received honoraria from Amgen, GlaxoSmithKline and Sanofi; EZ has received honoraria and has served in advisory role for Janssen, Bristol-Myers Squibb, Sanofi, Amgen, GlaxoSmithKline, Pfizer, Oncopeptides, Menarini-Stemline. MP, IS, MI, MT, EM, SM, RR, SB, SA, BT and IV declare no potential conflicts of interest.

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