Patient With RRMM, Cytopenias, COPD, and Progressive Bone Disease

This case illustrates a typical candidate for bispecific antibody therapy: a 67-year-old patient with triple class–exposed myeloma presenting with rapidly progressive disease, pathologic fractures, and declining performance status. Her history of chronic obstructive pulmonary disease (COPD) raises important considerations regarding infection risk, as respiratory infections represent the most common infectious complication in patients receiving BCMA-directed therapies. The choice between BCMA and GPRC5D targeting may be influenced by her respiratory comorbidities, with some clinicians preferring GPRC5D-directed therapy in patients with significant pulmonary disease due to lower infection rates.

The patient’s rapid disease progression and need for immediate intervention makes an off-the-shelf bispecific antibody the most appropriate choice over chimeric antigen receptor (CAR) T-cell therapy, which would require several weeks for manufacturing. Her multiple comorbidities, including diabetes and obesity, combined with her need for assistance with activities of daily living, make the dose flexibility offered by bispecific antibodies particularly attractive. The ability to hold doses, reduce intensity, or temporarily discontinue treatment provides crucial safety margins for patients with complex medical conditions who may not tolerate continuous therapy protocols.

Treatment selection between BCMA and GPRC5D targeting involves weighing efficacy data against tolerability profiles, with BCMA bispecifics offering robust clinical data and established response rates around 70%, while GPRC5D targeting may provide better tolerability in patients with respiratory comorbidities. Regardless of target selection, this patient will require comprehensive supportive care including prophylactic antimicrobials, careful monitoring for infectious complications, and proactive management of treatment-related toxicities. The case demonstrates how bispecific antibodies provide viable treatment options for patients who historically had limited therapeutic choices due to advanced disease and multiple comorbidities