Earlier Use of Bispecific Antibodies in Multiple Myeloma: Current Data and Remaining Questions
- Bispecific antibodies targeting plasma cell antigens BCMA and GPRCD5 redirect T cells to facilitate antimyeloma activity in patients who are heavily pretreated.
- Although bispecific antibodies are currently approved for patients with multiple myeloma (MM) who have had 4 prior lines of treatment, emerging data support earlier use after first relapse.
- Ongoing studies are exploring the role of bispecific antibodies as part of first-line treatment in MM.
Over the past 10 years, the growing therapeutic landscape for MM has led to an era of novel immunotherapeutic approaches that are more specific and tolerable and that have the ability to prolong survival. For example, anti-CD38 monoclonal antibodies are now standard components of first-line treatment. Although we are seeing unprecedented improvement in progression-free survival (PFS) with first-line options, most patients will eventually experience relapse, and there is a need for therapies that overcome resistance to prior therapies. T-cell–redirecting therapies, including bispecific antibodies and CAR T cells, are novel approaches that have demonstrated efficacy in treatment-refractory MM. Both are moving into earlier lines of treatment than originally studied in the fifth line and beyond. For example, both CAR T-cell products ciltacabtagene autoleucel and idecabtagene vicleucel are approved in the second line for lenalidomide-refractory MM based on superior efficacy when compared with standard antimyeloma regimens
There are currently 4 approved bispecific antibodies—3 target BCMA (teclistamab, elranatamab, and linvoseltamab), and 1 targets GPRC5D (talquetamab). At present, these are all approved after the fourth line of therapy based on single-agent studies that have shown high overall response rates in patients who are heavily pretreated. There is substantial potential for these bispecific antibodies to exert greater antimyeloma effects in earlier disease phases by averting T-cell exhaustion and clonal resistance that increases with progressive lines of therapy, allowing for better tolerance in patients who are less heavily treated. As such, several studies are exploring their role in earlier lines, including as part of upfront treatment, as shown in the Table.
Table. Ongoing Studies of Bispecific Antibodies in Newly Diagnosed MM
Abbreviations: cilta-cel, ciltacabtagene autoleucel; dara, daratumumab; DRd, daratumumab, lenalidomide, dexamethasone; DVRd, daratumumab, bortezomib, lenalidomide, and dexamethasone; elra, elranatamab; HDT, high-dose therapy; linvo, linvoseltamab; MRD, minimal residual disease; PFS, progression-free survival; RVd, revlimid/lenalidomide, velcade/bortezomib, dexamethasone; tal, talquetamab; tec, teclistamab.