Muhamed Baljevic, MD

Panelists discuss how despite the significant progress with bispecifics in relapsed/refractory multiple myeloma (R/R MM), major unanswered questions remain including optimal sequencing strategies (which represent the biggest challenge), how to implement bispecifics earlier in the treatment paradigm, and how to integrate them with other existing therapies in the evolving treatment landscape.

Panelists discuss how optimal sequencing strategies suggest using chimeric antigen receptor (CAR) T-cell therapy first when eligible, followed by switching targets (from B-cell maturation antigen [BCMA] to GPRC5D) upon relapse rather than staying with the same target, while acknowledging that sequential bispecific use may be challenging due to T-cell exhaustion and recommending “sandwiching” T-cell sparing agents like cereblon E3 ligase modulators (CELMoDs) between bispecifics to allow T-cell recovery. However, they note that monthly dosing schedules and treatment holidays may change these dynamics in the future.

Panelists discuss how the extended follow-up data from MonumenTAL-1 show consistent safety outcomes for talquetamab with manageable discontinuation rates due to skin changes and weight loss, while acknowledging that GPRC5D targeting creates unique toxicities including nail and skin changes that require proactive management strategies, particularly as treatment transitions from academic centers to community practice where quality-of-life considerations become increasingly important.

Panelists discuss how the OPTEC trial and other studies demonstrate that outpatient teclistamab administration with prophylactic tocilizumab is feasible and safe, with no cytokine release syndrome (CRS) events reported in community settings, while acknowledging that Risk Evaluation and Mitigation Strategies (REMS) requirements remain a significant barrier to broader community adoption despite the reality that most CRS is now grade 1-2 and manageable with supportive care, suggesting the field needs to follow lymphoma’s example of bispecifics without REMS restrictions.

Panelists discuss how real-world outpatient talquetamab data from Mayo Clinic show that 85% of patients can start treatment as outpatients with about 50% completing the entire step-up process without hospitalization, while different centers are developing varying approaches to cytokine release syndrome (CRS) management—from no prophylaxis with 50% admission rates to prophylactic tocilizumab with 3% admission rates—suggesting that practice preferences may ultimately determine which bispecific agents are favored based on factors like median time to CRS onset.

Panelists discuss how outpatient administration of talquetamab is becoming more feasible with proper patient selection, noting that although there are few absolute medical contraindications to bispecifics, they exercise caution in patients with dialysis dependency (due to different pharmacokinetics), spinal cord compression (due to inflammatory response concerns), decompensated heart failure, or active infections, while emphasizing that most myeloma patients who desire continued therapy should not be denied bispecific treatment.

Panelists discuss how to operationalize talquetamab dosing in community settings by addressing the main challenges of infection risk and skin toxicity through patient education, proactive monitoring protocols, and careful patient selection, with early community experience showing manageable toxicity rates and the importance of setting proper expectations about skin and nail changes as markers of drug activity rather than concerning adverse effects.

Panelists discuss how the emerging trispecific antibody (targeting both T cells and natural killer [NK] cells) has generated significant excitement with its unprecedented 100% overall response rate in B-cell maturation antigen (BCMA)–exposed patients, while incorporating lessons learned from earlier bispecifics such as starting with Q4 weekly dosing and built-in tocilizumab prophylaxis, although they acknowledge this breakthrough may completely reshape treatment sequencing strategies and create new challenges in determining optimal therapy combinations.

Panelists discuss how the availability of multiple B-cell maturation antigen (BCMA) bispecific agents (with linvoseltamab approved in Europe and other agents in development) creates beneficial competition that could drive down costs and provide more treatment options, while acknowledging that safety and efficacy profiles appear comparable across agents, making accessibility and convenience key differentiating factors for patient care.

Panelists discuss how recent long-term follow-up data for teclistamab and elranatamab reaffirm their effectiveness in relapsed/refractory multiple myeloma (R/R MM) with no new safety signals, while emphasizing that direct comparisons between B-cell maturation antigen (BCMA) bispecifics may not be fair due to evolving mitigation strategies, improved supportive care practices, and different study conditions including the impact of COVID-19 on early trials.

Panelists discuss how the extended median follow-up data from the MonumenTAL-1 trial demonstrate that Q2 weekly dosing of talquetamab shows superior progression-free survival (11.2 vs 7.5 months), duration of response (19.5 vs 7.5 months), and overall survival compared with weekly dosing, with particularly encouraging efficacy in high-risk cytogenetics and older patients while maintaining a manageable safety profile.

Panelists discuss how bispecific antibodies have evolved in relapsed/refractory myeloma treatment, highlighting recent data developments, the importance of NCCN guideline updates, including prophylactic tocilizumab recommendations, and strategies for improving toxicity management and community practice implementation.

Muhamed Baljevic, MD, considers the role of autologous stem cell transplantation for light chain amyloidosis in a peer perspective accompanying an article by Iuliana Vaxman, MD, and Angela Dispenzieri, MD.