Gurbakhash Kaur, MD

Following the presentation of the CARTITUDE-4 trial, the faculty discuss how the study findings may influence treatment strategies for relapsed/refractory multiple myeloma (R/R MM).

Dr. Cesar Rodriguez presents findings from the phase 3 CARTITUDE-4 trial, which compared ciltacabtagene autoleucel (cilta-cel) with standard-of-care regimens in patients with relapsed/refractory multiple myeloma (R/R MM) who were refractory to lenalidomide after one to three prior lines of therapy.

Dr. Prashant Kapoor reviews the pivotal phase 1/2 LINKER-MM1 study evaluating linvoseltamab, a BCMA × CD3 bispecific antibody, in heavily pretreated patients with relapsed/refractory multiple myeloma (R/R MM).

Dr. Shambavi Richard welcomes viewers to Cancer Network's FACE-OFF, introducing a debate-driven educational program focused on the evolving role of BCMA-targeted therapies in relapsed/refractory multiple myeloma (R/R MM).

Dr. Saad Usmani reviews key findings from the phase 3 CARTITUDE-4 trial and discusses the growing role of ciltacabtagene autoleucel (cilta-cel) in patients with second-line and earlier-relapse relapsed/refractory multiple myeloma. The discussion highlights the study population, including patients with lenalidomide-refractory disease and high-risk clinical features, as well as the significant progression-free survival benefit observed with BCMA-directed CAR T-cell therapy compared with standard triplet regimens. Dr. Usmani and the panel examine the depth and durability of response, including high rates of complete response and sustained MRD negativity, and discuss the concept of treatment-free remission as a unique advantage of CAR T-cell therapy. Faculty also explore practical considerations such as patient selection, manufacturing timelines, bridging therapy, disease burden control, and quality-of-life outcomes. The conversation further addresses important safety considerations, including cytokine release syndrome, neurotoxicity, Parkinsonism-like events, immune effector cell-associated enterocolitis, access challenges, and the logistical barriers associated with delivering CAR T-cell therapy in real-world multiple myeloma practice.

Dr. Thomas Martin opens this Cancer Network FACE-OFF program by introducing a debate-style discussion focused on one of the most rapidly evolving areas in relapsed/refractory multiple myeloma: treatment selection between BCMA-directed CAR T-cell therapy and bispecific antibody-based approaches in second-line and earlier-relapse disease. He outlines the unique format of the program, which combines clinical data review, expert debate, and case-based discussion to explore real-world treatment decision-making. Dr. Martin introduces Team Myeloma Mavericks, led by Dr. Saad Usmani and featuring Dr. Surbhi Sidana and Dr. Gurbakhash Kaur, and Team Myeloma Masters, led by Dr. Peter Voorhees with Dr. Amrita Krishnan and Dr. Hans Lee. The segment concludes with an overview of the pivotal studies that will frame the discussion, including CARTITUDE-4, MajesTEC-3, and MajesTEC-9, highlighting how emerging efficacy, durability, safety, and sequencing data are reshaping treatment strategies for patients with relapsed/refractory multiple myeloma.

Panelists discuss how high-risk disease biology and recent bispecific therapy heighten the need for timely, individualized sequencing and rigorous safety planning around infections, cytopenias, and early monitoring.

Panelists discuss how recent bispecific exposure does not necessarily preclude CAR T, but timing, disease tempo, infection/immune assessments, and realistic scheduling expectations shape readiness and planning.

Panelists discuss how clinicians set expectations for the acute toxicity window and monitoring while also considering how rising disease burden or prior BCMA exposure can influence efficacy and reinforce urgency of referral.

Panelists discuss how older patients with cardiac/renal comorbidities may still be appropriate CAR T candidates when conditions are well-managed, and why early evaluation protects eligibility and aligns care with patient goals.

Panelists discuss how complete referral information and evolving outpatient pathways (including shortened post-infusion monitoring requirements) can improve coordination, reduce logistical burden, and maintain safe follow-up.

Panelists discuss how transparent counseling on expected benefits, early-onset toxicities, and practical logistics (travel, caregiver needs, support resources) helps patients make confident decisions about CAR T.

Panelists discuss how early financial navigation and proactive payer coordination can mitigate insurance delays and out-of-pocket burdens that commonly derail CAR T access.

Panelists discuss how clearer communication and streamlined referral workflows (including dedicated navigation/support roles) can reduce uncertainty around scheduling, manufacturing timelines, and treatment capacity.

Panelists discuss how early referral drop-off is driven by awareness gaps, outdated perceptions of when CAR T should be used, travel/caregiver burdens, and process complexity—and which barriers are most addressable.

Panelists discuss how real-world CAR T outcomes in older or comorbid patients can mirror trial results when organ function, monitoring, and multidisciplinary support are optimized.

Panelists discuss how sequencing choices before third-line CAR T balance disease control and eligibility preservation, while avoiding prolonged therapies that could compromise later collection or outcomes.

Panelists discuss how prior BCMA-directed or bispecific therapy may affect T-cell fitness and CAR T planning, including the value of early referral and strategic washout/bridging approaches when feasible.

Panelists discuss how clinicians distinguish candidates for second-line versus third-line CAR T by weighing disease aggressiveness, relapse timing, cytogenetic risk, patient preferences, and toxicity tradeoffs.

Panelists discuss how differences in BCMA-directed CAR T constructs (including binding configuration and expansion kinetics) can influence toxicity timing, monitoring needs, and real-world product selection.

Panelists discuss how pivotal trials and real-world evidence have reinforced CAR T-cell therapy’s high response rates, deep remissions, and durable outcomes in relapsed/refractory multiple myeloma.

Panelists discuss how their key takeaways emphasize the importance of communication and collaboration between academic centers and community practices to ensure equitable access to bispecific therapies, highlighting that it’s an exciting time in myeloma treatment with patient-friendly options that can be administered closer to home, and concluding that virtually no patient should be denied exposure to bispecific therapy before discontinuing treatment, while anticipating that de-escalated Q4 weekly schedules and trispecific agents will transform current practice patterns in the coming years.

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.

Panelists discuss how managing a high-risk patient aged 64 years who progressed after 11 months on talquetamab with decreased B-cell maturation antigen (BCMA) surface expression presents challenging options, including switching to GPRC5D-targeting agents like talquetamab, pursuing clinical trials, or potentially using sequential bispecifics despite T-cell exhaustion concerns, while noting that the MonumenTAL-1 trial’s prior BCMA-directed therapy cohort showed promising 12-month progression-free survival, although the data are confounded by intervening therapies between treatments.

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.