Treatment history, not race or duffy-null status, predicts outcomes with teclistamab in Relapsed/Refractory multiple myeloma

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Abstract INTRODUCTION Bispecific antibodies represent a transformative therapy for relapsed/refractory multiple myeloma (RRMM). Teclistamab, the first FDA-approved B-cell maturation antigen (BCMA)-directed bispecific antibody, has demonstrated efficacy in clinical trials, but real-world outcomes may vary due to differences in baseline characteristics, treatment history, or genetic factors. Of particular interest, the Duffy-null phenotype, common in individuals of African ancestry and associated with constitutively lower neutrophil counts, has raised theoretical concerns about increased neutropenia-related complications with myelosuppressive therapies. We evaluated real-world teclistamab outcomes across racial and ethnic groups and examined whether Duffy antigen status influences hematologic toxicity or clinical outcomes. METHODS We conducted a retrospective study of patients with RRMM treated with standard-of-care teclistamab at MD Anderson Cancer Center between January 2023 and January 2024. Patients who received teclistamab as bridging therapy for chimeric antigen receptor (CAR) T therapy were excluded. Primary endpoints were progression-free survival (PFS) and overall response rate (ORR). Secondary endpoints included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, infections, and overall survival (OS). Group comparisons used chi-squared and Kruskal–Wallis tests. Multivariable Cox regression identified predictors of PFS. Logistic regression evaluated predictors of ORR. RESULTS Among 79 patients, 25 self-identified as Black (32%), 12 Hispanic/Latino (15%), and 42 White (53%). The cohort was 53% male with median age 70 years (interquartile range (IQR) 62.4-76.5). Duffy antigen phenotyping was available in 72 patients: 58 Duffy-positive and 14 Duffy-null (13 Black, 1 Hispanic). Significant baseline differences were seen by race/ethnicity. Hispanic patients were younger (median 57.5 vs 71.0 and 70.7 years for Black and White patients, respectively; p=0.02), more heavily pretreated (median 7.5 vs 4.0 and 5.0 prior lines; p=0.04), and had higher rates of prior autologous stem cell transplant (ASCT) (92% vs 56% and 79%; p=0.04). They also had lower baseline absolute neutrophil counts (ANC) (median 1.33 vs 2.14 and 2.24 × 10⁹/L; p=0.047) and platelets (median 87.5 vs 155 and 115.5 × 10⁹/L; p=0.01). Hispanic patients had lower ORR (36% vs 78% and 75%) and numerically shorter PFS (8.44 vs not reached (NR) and 16.46 months; p=0.098). In multivariable analysis, race/ethnicity was not independently associated with PFS (HR 0.99 for Hispanic vs White, 95% confidence interval (CI) 0.28-2.74, p=0.82; HR 0.99 for Black vs White, 95% CI 0.39-2.52, p=0.98). Worse PFS was linked to more prior lines of therapy (HR 1.23 per line, 95% CI 1.05-1.46, p=0.01), younger age (hazard ratio (HR) 0.96 per year, 95% CI 0.93-1.00, p=0.04), and prior ASCT (HR 4.11, 95% CI 0.96-17.53, p=0.056). Baseline cytopenias were not independently predictive after adjusting for treatment history. OS was similar across race/ethnic groups (p=0.94), though follow-up time was limited. Duffy-null status was not associated with worse neutropenia or outcomes. Baseline ANC (p=0.99), ANC nadir (p=0.84), infection rates (p=0.44), and PFS (p=0.72) were similar between Duffy-null and Duffy-positive patients. Despite greater frequency and severity of cytopenias, Hispanic patients had comparable infection rates compared to Black and White patients but required more supportive care (granulocyte colony-stimulating factor use, p=0.02). Time to first infection, total infections, treatment delays due to infection, and infection-related discontinuations were equivalent between groups. Rates of CRS and ICANS were similar across all groups. DISCUSSIONRace, ethnicity, and Duffy-null status were not independently associated with teclistamab efficacy or safety. Observed outcome differences were explained by treatment history (prior lines of therapy and ASCT) and patient age rather than race/ethnicity itself. Duffy-null patients did not have higher rates of neutropenia, infections, or treatment delays, suggesting no added clinical risk. These findings support equitable use of teclistamab regardless of ancestry or genotype. Earlier integration of teclistamab into treatment may improve outcomes across all groups. Larger studies are needed to confirm these findings and guide sequencing strategies.

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