Abstracts
PO55
Association of SGLT2 Inhibitor Use with Outcomes After Bispecific Antibody Therapy for Multiple Myeloma: A Multi-database Study
Introduction/Background/Significance: T-cell-engaging bispecific antibodies (BsAb) have become integral therapies for relapsed or refractory hematologic malignancies but are frequently complicated by immune-mediated toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).1 Metabolic syndrome is a known risk factor for the development of hematologic malignancy and is a poor prognostic indicator.2,3 Over the last decade, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have become increasingly prescribed agents with growing evidence of reducing the incidence of cancer and improving cancer-related outcomes.4 Whether SGLT2i use modifies the effectiveness or toxicity of T-cell-engaging bispecific antibodies (BsAbs) in multiple myeloma (MM) is understudied. We hypothesized that SGLT2i use at BsAb initiation would be associated with improved survival and reduced incidence of severe immune-effector toxicity given the known immunomodulatory properties.
Materials and Methods/Case Presentation/Objective: We conducted complementary pharmacovigilance with FDA Adverse Event Reporting System (FAERS) and longitudinal real-world cohort analyses with the Mayo Clinic Platform (MCP). Deduplicated FAERS reports from 2020 Q1 through 2026 Q1 involving teclistamab, talquetamab, elranatamab, and linvoseltamab were identified. An SGLT2i was required to be listed as a concomitant medication. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The MCP cohort included adults with MM who initiated one of these BsAbs through February 2026. The index date was first BsAb administration. SGLT2i exposure was defined as having any of the class of medication administered at least once prior to the index date. The primary outcome was 90-day overall survival, for which a hazard ratio (HR) with 95% CI was calculated. Secondary outcomes were blood tranfusions, CRS, and ICANS at 90 days, for which rate ratios (RR) with 95% CIs were calculated.
Results/Description/Main Outcome Measure(s): The FAERS cohort included 6,747 reports containing the myeloma-directed BsAbs, of which 33 listed an SGLT2i. Concomitant SGLT2i use was not associated with higher ROR of CRS (21.2% vs 21.9%; ROR, 0.96; 95% CI, 0.41-2.2) or ICANS (6.1% vs. 7.5%; ROR, 0.79; 95% CI, 0.19-3.3). The MCP cohort included 325 patients who received either teclistamab, talquetamab, or elranatamab, including 50 with SGLT2i exposure and 275 without baseline use. There was no difference in overall survival between the cohorts (90 day survival: 80.5% in the SGLT2i group vs. 83.0% in the non-SGLT2i group, HR 1.16, 95% CI 0.56-2.4), number of patients requiring blood transfusions (RR 0.56, 95% CI 0.29-1.06) or ICANS (RR 0.80, 95% CI 0.11-5.7). However, patients with SGLT2i exposure had significantly less CRS compared to those without SGLT2i exposure (RR 0.64, 95% CI 0.41-0.99).
Conclusion(s).:
Trademarked Items:
References: 1. https://www.nature.com/articles/s41573-024-00896-6
2. https://diabetesjournals.org/care/article/35/11/2402/31077/Metabolic-Syndrome-and-Risk-of-CancerA-systematic
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC12924594/
4. https://pmc.ncbi.nlm.nih.gov/articles/PMC12830215/
Materials and Methods/Case Presentation/Objective: We conducted complementary pharmacovigilance with FDA Adverse Event Reporting System (FAERS) and longitudinal real-world cohort analyses with the Mayo Clinic Platform (MCP). Deduplicated FAERS reports from 2020 Q1 through 2026 Q1 involving teclistamab, talquetamab, elranatamab, and linvoseltamab were identified. An SGLT2i was required to be listed as a concomitant medication. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The MCP cohort included adults with MM who initiated one of these BsAbs through February 2026. The index date was first BsAb administration. SGLT2i exposure was defined as having any of the class of medication administered at least once prior to the index date. The primary outcome was 90-day overall survival, for which a hazard ratio (HR) with 95% CI was calculated. Secondary outcomes were blood tranfusions, CRS, and ICANS at 90 days, for which rate ratios (RR) with 95% CIs were calculated.
Results/Description/Main Outcome Measure(s): The FAERS cohort included 6,747 reports containing the myeloma-directed BsAbs, of which 33 listed an SGLT2i. Concomitant SGLT2i use was not associated with higher ROR of CRS (21.2% vs 21.9%; ROR, 0.96; 95% CI, 0.41-2.2) or ICANS (6.1% vs. 7.5%; ROR, 0.79; 95% CI, 0.19-3.3). The MCP cohort included 325 patients who received either teclistamab, talquetamab, or elranatamab, including 50 with SGLT2i exposure and 275 without baseline use. There was no difference in overall survival between the cohorts (90 day survival: 80.5% in the SGLT2i group vs. 83.0% in the non-SGLT2i group, HR 1.16, 95% CI 0.56-2.4), number of patients requiring blood transfusions (RR 0.56, 95% CI 0.29-1.06) or ICANS (RR 0.80, 95% CI 0.11-5.7). However, patients with SGLT2i exposure had significantly less CRS compared to those without SGLT2i exposure (RR 0.64, 95% CI 0.41-0.99).
Conclusion(s).:
While the pharmacovigilance data did not show higher RORs of CRS and ICANS, the real-world MCP cohorts showed that SGLT2i use was associated with reduced incidence of CRS. These findings suggest that SGLT2i may modify BsAb toxicity. Future studies exploring immunotoxicity severity and survival outcomes is crucial to further delineate the role of SGLTis in MM outcomes.
Trademarked Items:
References: 1. https://www.nature.com/articles/s41573-024-00896-6
2. https://diabetesjournals.org/care/article/35/11/2402/31077/Metabolic-Syndrome-and-Risk-of-CancerA-systematic
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC12924594/
4. https://pmc.ncbi.nlm.nih.gov/articles/PMC12830215/
