Work

Rethinking immunotherapy sequencing in multiple myeloma: a conceptual adaptive immunotherapy sequencing model

Year: 2026

Type: article

Abstract: Background: Chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs) have transformed treatment for relapsed/refractory multiple myeloma (RRMM). Contemporary guidelines increasingly incorporate prior antigen-directed exposure, disease kinetics, patient fitness, toxicity, access, and patient preference. However, a prospectively validated framework that jointly operationalizes immune fitness, tumor antigen status, and treatment feasibility for sequencing T-cell-redirecting therapies is not available. Main body: This Perspective introduces the Adaptive Immunotherapy Sequencing Model (AISM), an author-proposed framework for research and multidisciplinary discussion. AISM proposes that sequencing should be studied in relation to two evolving biological domains: the capacity of the host T-cell compartment to support therapy and the probability that the relevant tumor antigen remains therapeutically actionable. The model uses provisional 0-10 research constructs for T-cell fitness and antigen-escape risk to make these domains explicit. AISM hypothesizes that, for eligible patients with early RRMM and feasible access, referral for BCMA-directed CAR-T before prolonged exposure to T-cell-redirecting BsAbs may preserve a potentially favorable treatment option. It also recognizes that off-the-shelf BsAbs may be necessary when disease tempo, frailty, access, or patient preference make CAR-T impracticable. After prior BCMA-directed therapy, an antigen-switching approach is biologically plausible, but antigen loss is not universal and other mechanisms of resistance must be considered. Conclusions: AISM provides a testable framework for prospective comparative studies. Such studies should evaluate whether biologically informed sequencing improves progression-free survival (PFS), while also assessing overall survival, toxicity, infections, treatment-free time, feasibility, and patient-reported outcomes.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1897153

Author: Aliaa Khalili

Institution: Al-Quds University

Language: English

Topic: Multiple Myeloma Research and Treatments

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801