Cellular and T cell engager Immunotherapy

Category: Cellular and T cell engager Immunotherapy

Immune Correlates of Response to T-Cell Engaging Bispecific Antibody Treatments in Multiple Myeloma

(PA-032) Immune Correlates of Response to T-Cell Engaging Bispecific Antibody Treatments in Multiple Myeloma

Wednesday, September 17, 2025

Ramzi Hamouche, MD

Hematology-Oncology Fellow
University of Connecticut

Introduction: Bispecific antibodies (BsAbs) are a promising therapy for patients with relapsed or refractory multiple myeloma (RRMM). Three BsAbs—BCMA-directed teclistamab and elranatamab, and GPRC5D-directed talquetamab—are FDA approved. Responders typically present with higher absolute lymphocyte counts (ALC) and preserved CD4 and CD8 T-cell function, whereas non-responders may have lymphopenia or dysfunctional T-cell profiles. Prior studies suggest higher proportions of CD4⁺ cells may predict more durable response to BCMA-directed BsAbs. We evaluated whether dynamic changes in lymphocyte subsets during early BsAb treatment correlate with clinical response.

Methods: We retrospectively reviewed a patient cohort with RRMM who received BsAb therapy at a single academic center. Baseline ALC, CD4%, and CD8% were recorded alongside clinical characteristics. Dynamic changes in ALC and T-cell subsets were assessed at three pre-specified timepoints: pre-treatment (T0), post-step-up/after one cycle (T1), and after two or three cycles (T2). We calculated changes (Δ) in ALC, CD4%/ALC, and CD8%/ALC between timepoints and assessed their association with clinical response using Student’s t-test. Statistical analysis was performed using Python 3.12.9 with SciPy 1.15.3.

Results: Of 31 patients (19 M/12 F, median age 69 y), 23 received BCMA-targeting agents (teclistamab 19, elranatamab 4) and 8 received GPRC5D-targeting talquetamab. Patients had a median of six prior LOT (3–11); 10 had prior BsAb, and 15 had prior ASCT. 13 had extramedullary disease. At T0, median CD4 was 319 cells/μL (18–927), CD8 was 395 cells/μL (13–2760), ALC was 1.0 cells/μL (0–3.8). ΔALC between timepoints did not correlate with response. Baseline-to-post-cycle-1 ΔCD4%/ALC correlated with response for BCMA-directed BsAbs (p = 0.007) and the combined cohort (p = 0.006); no significant correlations were seen at the later interval. Similarly, baseline-to-post-cycle-1 ΔCD8%/ALC correlated with response in the overall cohort (p = 0.0007) and in BCMA-treated patients (p = 0.0005). Post-cycle-1 to cycle-2/3 ΔCD8%/ALC showed no significant association with response. Baseline-to-cycle-2/3 ΔCD8%/ALC was significant for the overall cohort (p = 0.0009).

Conclusions: Our findings suggest early increases in peripheral CD4+ and CD8+ T-cell percentages correlate with improved response to BsAb therapy in RRMM. The strongest associations were seen with CD8% changes from pre-treatment to post-step-up and to post-cycle 2 or 3. Baseline CD8% alone did not correlate with response, highlighting the assessment of dynamic immune changes over static pre-treatment measures only. Peripheral CD4+ and CD8+ T-cell monitoring needs to be evaluated further as a biomarker of BsAb response. Larger prospective studies are needed to validate these findings and explore mechanistic underpinnings, given limitations of our sample size, particularly in the GPRC5D cohort. Follow-up will clarify whether these immune shifts predict durable, late responses.