Clinical Scenario 2 With Bispecifics in R/R MM
Panelists discuss how a woman aged 69 years with standard-risk relapsed/refractory multiple myeloma (R/R MM), significant comorbidities including chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD), and history of respiratory infections would be a reasonable candidate for talquetamab despite infection concerns, citing that GPRC5D-targeting agents show much lower infection rates (less than 10%) compared with B-cell maturation antigen (BCMA) bispecifics (around 50%) due to preferential expression on malignant cells rather than normal B cells, with no requirement for prophylaxis and evidence of preserved humoral immunity including COVID-19 vaccine responses.
EP: 1.MonumenTAL-1: Outcomes From the Extended Median Follow-Up Data
EP: 2.MonumenTAL-1: Outcomes From the Extended Median Follow-Up Data (Part 2)
EP: 3.Data Review of Teclistamab and Elranatamab in R/R MM
EP: 4.Expert Opinion on Modern Availability of Several Agents
EP: 5.Future of R/R MM: Emerging Bispecifics and Trispecifics
EP: 6.Optimal Dosing of Talquetamab
EP: 7.Optimal Dosing of Talquetamab (Part 2)
EP: 8.Talquetamab: Real-World Outcomes With Outpatient Dosing
EP: 9.Teclistamab: OPTEC Trial Overview
EP: 10.MonumenTAL-1: Safety Outcomes
EP: 11.Optimal Sequencing Strategies With Bispecifics in R/R MM
EP: 12.Bispecifics in R/R MM: Unanswered Questions
EP: 13.Clinical Scenario 1 With Bispecifics in R/R MM
EP: 14.Clinical Scenario 2 With Bispecifics in R/R MM
Segment 14 Summary: Clinical Scenario 2 With Bispecifics in R/R MM
This case involves a woman aged 69 years with standard-risk R/R MM following 4 lines of therapy, including VRd, chimeric antigen receptor T-cell therapy, and pomalidomide-bortezomib-dexamethasone, with no prior BCMA-targeted therapy exposure. She presents with both biochemical and radiologic disease progression but has significant comorbidities, including COPD with reduced ejection fraction (45%), stage 3 chronic kidney disease, and a history of recurrent respiratory infections and hospitalizations. The clinical team is considering teclistamab with every-2-week dosing but has concerns about infectious complications given her pulmonary comorbidities and infection history.
Despite the patient’s significant comorbidities and infection history, she would not have absolute contraindications to bispecific therapy. The key consideration is the differential infection risk profiles between BCMA-targeted and GPRC5D-targeted bispecific antibodies. BCMA is more preferentially expressed on malignant plasma cells compared with normal B cells, which theoretically reduces the impact on normal immune function. Clinical data support this theoretical advantage, with BCMA-targeted therapies showing much lower infection rates compared with GPRC5D-targeted agents—approximately 19% vs over 50% grade 3 or higher infection rates, respectively.
For this high-risk patient, BCMA-targeted therapy like teclistamab represents a more reasonable option given the lower infectious complications profile. Additionally, the MonumenTAL-1 study data showed that patients did not experience COVID-19–related deaths, maintained vaccine responses, preserved humoral immunity, and did not require opportunistic infection prophylaxis, differentiating GPRC5D-targeted therapy from other immunosuppressive treatments. However, given her respiratory comorbidities and infection history, careful monitoring, appropriate prophylaxis strategies, and potentially inpatient initiation for close observation would be prudent considerations to ensure safe administration while maximizing therapeutic benefit.
