Early Treatment Failure in Real-World Bispecific-Antibody Therapy for Relapsed or Refractory Multiple Myeloma: Pathways, Determinants, and Measurement Gaps
- 1Department of Hematology, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China
- 2Department of Oncology Medicine, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China
Abstract
T-cell–redirecting bispecific antibodies have substantial antimyeloma activity in relapsed or refractory multiple myeloma, but their effectiveness in routine practice depends on patients reaching treatment and maintaining exposure long enough to achieve disease control. Clinical deterioration before dosing, incomplete step-up dosing, interrupted exposure, progression before response, infection, and early death can limit benefit. This narrative review integrates clinical trials, commercial cohorts, translational studies, and treatment-delivery evidence to examine these failures from treatment selection to durable benefit. Commercial cohorts show substantial early post-initiation mortality, predominantly associated with progressive myeloma. Drug-specific observations distinguish delayed response in clinically stable patients from established progression, relate residual tumor burden after cytoreduction to subsequent disease control, and place prior BCMA-directed therapy in the context of the preceding treatment course. Host and marrow reserve, immune fitness, and infection are examined in relation to disease control and treatment continuity. Current studies commonly begin at first administration and report response among evaluable patients, incompletely capturing pre-initiation loss and reasons for non-evaluability. Future datasets should link treatment-intended and treatment-initiated populations, retain reasons for missed transitions, record actual exposure, and distinguish unplanned interruption from response-adapted dose modification. Analyses should align time origin with the clinical question and account for response, supportive interventions, and dose modification as time-dependent variables when appropriate. As bispecific antibodies move earlier, prognostic associations from heavily pretreated cohorts require reassessment. Reporting across treatment stages can complement response and survival endpoints by distinguishing aggressive disease, insufficient exposure, competing morbidity, and treatment-delivery constraints.
Related
- 1187 Safety and efficacy of cesalatamig, a novel PD-1/VEGF bispecific antibody, as monotherapy in PD-(L)1–resistant/refractory NSCLC: Results from global, multicenter, open-label phase 1/2 studies
- Impact of granulocyte colony-stimulating factors on cytokine release syndrome during bispecific antibody initiation in relapsed/refractory multiple myeloma
- Molecular Design and Preclinical Evaluation of GenSci143, a Novel B7-H3–Directed and PSMA-Directed Bispecific Antibody–Drug Conjugate, for the Treatment of Prostate Cancer
- PF chemotherapy combined with a PD-1/CTLA-4 bispecific antibody as first-line treatment in patients with recurrent/metastatic head and neck squamous cell carcinoma: a prospective, single-arm, phase II clinical study
- Treatment Optimization with Add-On Kampo Therapy in Highly Refractory Migraine Patients with Inadequate Response or Re-Worsening During CGRP Monoclonal Antibody Therapy: A Real-World Treatment Episode Analysis
BibTeX
@article{qi2026early,
title = {{Early Treatment Failure in Real-World Bispecific-Antibody Therapy for Relapsed or Refractory Multiple Myeloma: Pathways, Determinants, and Measurement Gaps}},
author = {Qi Qi and Bing Han and Runshi Fu},
journal = {OncoTargets and Therapy},
year = {2026},
month = nov,
doi = {10.2147/ott.s653346},
url = {https://doi.org/10.2147/ott.s653346},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Early Treatment Failure in Real-World Bispecific-Antibody Therapy for Relapsed or Refractory Multiple Myeloma: Pathways, Determinants, and Measurement Gaps
AU - Qi Qi
AU - Bing Han
AU - Runshi Fu
PY - 2026
DA - 2026/11/01
JO - OncoTargets and Therapy
DO - 10.2147/ott.s653346
UR - https://doi.org/10.2147/ott.s653346
AB - T-cell–redirecting bispecific antibodies have substantial antimyeloma activity in relapsed or refractory multiple myeloma, but their effectiveness in routine practice depends on patients reaching treatment and maintaining exposure long enough to achieve disease control. Clinical deterioration before dosing, incomplete step-up dosing, interrupted exposure, progression before response, infection, and early death can limit benefit. This narrative review integrates clinical trials, commercial cohorts, translational studies, and treatment-delivery evidence to examine these failures from treatment selection to durable benefit. Commercial cohorts show substantial early post-initiation mortality, predominantly associated with progressive myeloma. Drug-specific observations distinguish delayed response in clinically stable patients from established progression, relate residual tumor burden after cytoreduction to subsequent disease control, and place prior BCMA-directed therapy in the context of the preceding treatment course. Host and marrow reserve, immune fitness, and infection are examined in relation to disease control and treatment continuity. Current studies commonly begin at first administration and report response among evaluable patients, incompletely capturing pre-initiation loss and reasons for non-evaluability. Future datasets should link treatment-intended and treatment-initiated populations, retain reasons for missed transitions, record actual exposure, and distinguish unplanned interruption from response-adapted dose modification. Analyses should align time origin with the clinical question and account for response, supportive interventions, and dose modification as time-dependent variables when appropriate. As bispecific antibodies move earlier, prognostic associations from heavily pretreated cohorts require reassessment. Reporting across treatment stages can complement response and survival endpoints by distinguishing aggressive disease, insufficient exposure, competing morbidity, and treatment-delivery constraints.
SN - 1178-6930
ER -