The bispecific blind spot: Uncovering real-world inequities in diffuse large B-cell lymphoma, follicular lymphoma, and multiple myeloma therapy access Free

Introduction: Bispecific antibodies (BsAbs) and CAR T-cell therapy (CAR T) represent significant advancements in hematologic malignancy treatment. Prior research indicates inequities in access to BsAbs, but the influence of social determinants of health (SDOH) on real-world access remains unclear.

This study examined the demographic and clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and multiple myeloma (MM) receiving BsAbs and CAR T, and assessed inequities in BsAbs treatment initiation by race/ethnicity, SDOH, and practice-level factors.

Methods:This retrospective cohort study used the US-based, electronic health record-derived, deidentified Flatiron Health Research Database. The study cohort included patients with DLBCL/FL on at least third-line and those with MM on at least fifth-line therapy between 01/01/2022 - 5/31/2025.

Differences in patient characteristics were assessed using χ² and Fisher exact tests. Inequities in BsAbs initiation were assessed using subdistribution hazard ratios (HRs) with cumulative incidence functions, treating death as a competing risk. Primary exposures included age, sex, race/ethnicity, and area-level SDOH factors. Models adjusted for demographic and clinical factors, consistent with the Institute of Medicine framework. Clinically adjusted models included ECOG status and high-risk cytogenetic aberrations (HRCA), defined as MYC gene rearrangement with rearrangement of either BCL2 or BCL6 for DLBCL/FL and del17p, del1pl, or t(4;14), t(14;16), t(14;20) with 1q21 amplification/gain for MM by fluorescence in situ hybridization. Practice-level associations were modeled using quasi-Poisson regression with robust standard errors.

Results: Of 1,903 patients included in this study, 219 (12%) received BsAbs only, 403 (21%) CAR T only, and 119 (6%) received both. Patients treated with BsAbs (compared to those not treated with BsAbs) were more likely to be diagnosed with MM (69%), exhibit HRCA (DLBCL: 21% vs 8%; FL: 8% vs 5%, MM: 43% vs 25%), and receive care at academic centers (46%). No significant differences were observed between BsAbs and non-BsAbs patients with respect to birth sex, urbanicity, and residence in a medically underserved area. There were no observed differences in receipt of bispecific in the earliest eligible line by practice-level characteristics. Practice-level characteristics were not associated with BsAbs receipt in the earliest eligible line.

Among those treated with BsAbs only or CAR T only, BsAbs patients were older (≥65 y/o: 51% vs 36% of CAR T patients). Non-Latinx (NL) Black patients (14% vs 8%) and patients with MM (54% vs 46%) were more likely to receive BsAbs compared to CAR T. Additionally, compared with NL-White patients, NL-Asian patients were more likely to initiate BsAbs (HR: 2.11; 95% CI: 1.26-3.54). Most (92%) of the 119 patients who received both CAR T and BsABs were treated with CAR T followed by BsAbs.

In terms of SDOH factors, BsAb initiation was higher among patients from the highest socioeconomic status (SES) neighborhoods relative to patients from the lowest SES neighborhoods (highest quintile HR: 1.67; 95% CI: 1.11-2.53), with similar trends in clinically-adjusted models. BsAb initiation was lower among patients in predominantly Latinx neighborhoods relative to those in predominantly White neighborhoods (HR: 0.48; 95% CI: 0.25-0.91), a trend also seen among patients in Black neighborhoods (HR: 0.62; 95% CI: 0.36-1.06). Notably, the relationship between predominantly Latinx neighborhood residence and BsAbs initiation was fully explained by differences in ECOG and HRCA (HR: 0.41; 95% CI: 0.11-1.53).

Conclusions: We observed socioeconomic and demographic inequities in real-world access to novel BsAbs therapies among patients with DLBCL, FL, and MM. Specifically, patients living in lower SES areas and in predominantly Latinx neighborhoods had delayed BsAbs initiation. Although we observed higher BsAbs use among NL-Black patients relative to NL-White patients, these findings may be largely driven by higher CAR T use among NL-White patients relative to NL-Black patients, as shown in prior research. Nonetheless, these findings underscore the necessity of addressing systemic barriers to novel therapies to ensure equitable outcomes for all patients.