Abstract

 

Background

The best treatment approach after B-cell maturation antigen (BCMA)-directed therapy in relapsed/refractory

multiple myeloma (MM) remains unclear. This question is becoming increasingly important as BCMA-directed

chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies, and antibody-drug conjugates (ADCs) are

used earlier in the disease course. We reviewed the available data on subsequent T cell–redirecting therapy after

prior BCMA exposure and compared outcomes with BCMA retargeting vs switching to a non-BCMA target.

 

Methods

We searched PubMed and major hematology/oncology meeting abstracts, including ASH, ASCO, EHA/HemaSphere,

and SOHO, from 2022 to 2025 for studies of relapsed/refractory MM reporting outcomes following prior

BCMA-directed therapy. Eligible studies included patients who received subsequent T cell–redirecting therapy

and reported extractable outcomes for the prior-BCMA-exposed subgroup. Reviews, trial-in-progress abstracts,

preclinical studies, biomarker-only reports, ADC-only studies, and reports without extractable post-BCMA outcomes

were excluded. When overlapping cohorts were identified, the latest, most complete, or full-publication

source was used. Crude pooled objective response rates (ORRs) were calculated by sequencing strategy.

 

Results

Seven nonoverlapping cohorts were included. BCMA retargeting included teclistamab, elranatamab, ide-cel, or

cilta-cel after prior BCMA-directed therapy. Across four primary BCMA retargeting cohorts, crude ORR was

55.4% (108 of 195; 95% Wilson CI, 48.4%–62.2%). Median progression-free survival, when reported, ranged

from 3.2 to 9.1 months. Non-BCMA target switching, including GPRC5D- and FcRH5-directed therapy, showed

a crude ORR of 74.5% (35 of 47; 95% Wilson CI, 60.5%–84.7%) across three smaller cohorts. Because of

differences in prior BCMA modality, patient selection, refractoriness, and follow-up, these results should be

interpreted descriptively rather than as a direct comparison. A mixed post-BCMA salvage series showed lower

activity and was not pooled with T cell–redirecting strategies.

 

Conclusions

Responses after prior BCMA-directed therapy remain possible, but outcomes vary depending on the subsequent

strategy. BCMA retargeting showed consistent but modest activity, whereas switching to a non-BCMA T cell–

redirecting target showed numerically higher response rates in smaller cohorts. Although current data remain

limited and heterogeneous, they suggest that target switching may be an important strategy after BCMA exposure

and should be studied prospectively.

 

ASH: American Society of Hematology, ASCO: American Society of Clinical Oncology, cilta-cel: ciltacabtagene

autoleucel, EHA: European Hematology Association, FcRH5: Fc receptor-homolog 5, GPRC5D: G-protein coupled

receptor family C group 5 member D, ide-cel: idecabtagene vicleucel, SOHO: Society of Hematologic Oncology

 

Keywords

MM, relapsed/refractory, BCMA, post-BCMA sequencing, T-cell redirection