Efficacy Patterns and Treatment Selection Rationale in R/R MM

Dr. Costa analyzes efficacy patterns for patients with advanced multiple myeloma after 3-4 prior therapy lines. Across single-arm trials for bispecific T-cell engagers, response rates range from the low 60%s to mid-70% regardless of specific agents. Duration of response can exceed 2 years, with progression-free survival (PFS) averaging 1 to 2 years. However, analysis reveals two distinct populations: approximately 25% to 30% represent non-responders creating sharp PFS curve drops, whereas patients achieving responses by months 1 to 2 demonstrate very durable responses.

Dr. Costa describes bispecific T-cell engagers as operating in "all-or-nothing" patterns, with early non-responder identification and exceptionally durable responses among responders. Predictive factors for non-response include high-risk cytogenetics, high disease burden, extramedullary disease, and ISS stage III disease. Although these patients can respond, likelihood decreases and duration shortens.

Several improvement strategies exist, with earlier therapy use being Dr. Costa's preferred approach. He anticipates transitioning bispecific agents to earlier treatment lines, making late-stage high disease burden scenarios increasingly uncommon. Current combination strategies show promise, particularly teclistamab plus talquetamab for extramedullary disease, achieving response rates exceeding 70% with surprising durability.

For this 72-year-old patient seeking community-based treatment, Dr. Costa emphasizes no robust clinical data support alternative therapies for triple-class refractory patients with 4 prior lines. He advocates against perceptions that T-cell engagers are overly specialized, noting successful use in patients with significant comorbidities and advanced age with manageable toxicity profiles.