Bispecifics in R/R MM: Unanswered Questions
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.
Optimal Sequencing Strategies With Bispecifics in R/R MM
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.
Teclistamab: OPTEC Trial Overview
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.
Talquetamab: Real-World Outcomes With Outpatient Dosing
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.
Optimal Dosing of Talquetamab (Part 2)
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.
Future of R/R MM: Emerging Bispecifics and Trispecifics
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.
Expert Opinion on Modern Availability of Several Agents
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.
Data Review of Teclistamab and Elranatamab in R/R MM
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.
MonumenTAL-1: Outcomes From the Extended Median Follow-Up Data (Part 2)
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.
MonumenTAL-1: Outcomes From the Extended Median Follow-Up Data
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.
CAR T-Cell Therapy in Multiple Myeloma: Lessons Learned and Key Takeaways
January 31st 2025Panelists discuss how UCSF Health has learned that successful integration of CAR T-cell therapy in multiple myeloma requires multidisciplinary collaboration, patient selection optimization, and management of toxicities. Future research includes exploring CAR T-cell therapy in earlier treatment lines and combining it with novel agents to enhance efficacy.
Example of Successful Collaboration with a Referring Community Practice
January 31st 2025Panelists discuss collaborating with community practices on CAR T-cell therapy for multiple myeloma through joint clinical trials, patient education programs, and shared data initiatives. These partnerships enhance treatment access, foster innovation, and improve patient outcomes across diverse settings.
CAR T-Cell Therapy: CAR T-Cell therapy Process and Bridging Therapy
January 17th 2025Panelists discuss how CAR T-cell therapy involves engineering a patient’s T cells to target cancer cells. The process includes cell collection, genetic modification, expansion, and reinfusion and streamlines the process with integrated workflows. Bridging therapy is provided in-house to treat patients awaiting CAR-T infusion.
Referral Process for CAR T-Cell Therapy: Initial Contact Through Patient Evaluation and Selection
January 17th 2025Panelists discuss how the typical CAR T-cell therapy referral process begins with community physicians contacting the treatment center. The patient undergoes a thorough evaluation, including medical history, eligibility criteria, and pretreatment assessments before final selection for therapy.
Decision Points for Using CAR T-Cell Therapy in Early Lines of Treatment
January 13th 2025Panelists discuss how, when considering earlier lines of CAR T-cell therapy for relapsed/refractory multiple myeloma, key institutional factors include patient fitness/age, cytogenetic risk status, prior therapy response duration, and BCMA expression levels. Manufacturing timelines, financial considerations, and center-specific outcomes data also influence timing decisions. For patients receiving early-line CAR T therapy, subsequent treatment options typically focus on novel agent combinations or clinical trials exploring additional cellular therapies, with choices guided by response duration to CAR T and the patient’s individual disease characteristics and treatment goals.
Second-Line Treatment for R/R Multiple Myeloma: Who Is the “Right Patient”?
January 13th 2025Panelists discuss how, for second-line treatment of relapsed/refractory multiple myeloma (R/R MM), patients suitable for CAR T-cell (cilta-cel vs ide-cel) therapy typically have a poor prognosis with limited response to prior therapies. Institutional guidelines focus on factors such as prior lines of therapy, organ function, and cytogenetics. Non-medical factors, such as geographic access and financial constraints, also influence CAR T-cell therapy referral eligibility.
Panelists discuss how community centers can effectively implement bispecific antibody therapy for patients with relapsed/refractory multiple myeloma, addressing challenges such as staff training, patient monitoring, and managing potential adverse events in a non-academic setting.
Initial Impressions of the CEPHEUS Clinical Trial in Transplant Not-Preferred NDMM
November 26th 2024Panelists discuss how the CEPHEUS trial’s demonstration of improved progression-free survival with daratumumab-VRd versus VRd alone in transplant not-preferred NDMM provides compelling evidence for quadruplet therapy in this setting, though considerations of cost, toxicity management, and patient selection remain important factors in implementation.
Panelists discuss how to approach treatment decisions and management strategies for a 58-year-old woman with relapsed/refractory multiple myeloma who is post-autologous stem cell transplant, MRD-negative, and currently receiving bispecific antibody therapy, considering factors such as prior treatments, response duration, and long-term treatment goals.
Panelists discuss how optimizing dosing intervals and carefully considering combination strategies for bispecific antibodies in relapsed/refractory multiple myeloma could enhance treatment efficacy while managing toxicities and improving patient quality of life.
Insights of MAIA, BENEFIT, and IMROZ Trials on Frontline Treatment for Transplant Not-Preferred NDMM
November 19th 2024Panelists discuss how recent clinical trials have demonstrated improved outcomes with antibody-containing regimens and biomarker-driven approaches in patients with transplant not-preferred newly diagnosed multiple myeloma (NDMM).
Sequencing Therapies in Relapsed Refractory Multiple Myeloma: Bispecifics and CAR T-Cell Therapies
Panelists discuss how the optimal sequencing of bispecific antibodies and CAR T-cell therapies in relapsed/refractory multiple myeloma could maximize treatment efficacy and improve patient outcomes in this challenging disease setting.
OPTec: Outpatient Step Up Administration of Teclistamab: Implications in Real-World Practice
Panelists discuss how the OPTec study, which explores outpatient step-up administration of teclistamab, could impact real-world practice by potentially improving patient convenience and reducing healthcare resource utilization in the treatment of multiple myeloma.
Deciding Between Quadruplet and Triplet Therapy in Transplant-Preferred NDMM: Key Considerations
November 12th 2024Panelists discuss how the decision between quadruplet versus triplet therapy depends on multiple factors, including cytogenetic risk status, insurance coverage/drug access, patient fitness to tolerate additional toxicity, and the strength of evidence supporting improved outcomes with 4-drug combinations.
Prophylactic Tocilizumab in MajesTEC-1 for the Reduction of CRS
Panelists discuss how prophylactic use of tocilizumab in the MajesTEC-1 trial may reduce the incidence and severity of cytokine release syndrome (CRS) in patients receiving bispecific antibody therapy for multiple myeloma, potentially improving treatment safety and tolerability.