Ajai Chari, MD

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.

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.

Panelists 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.

Panelists 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.

Panelists discuss how challenges in the CAR T referral process include delayed referrals, patient logistics, and managing expectations. One institution addresses these through streamlined communication, patient education, and clear referral guidelines. Community physicians should refer early on, ensure candidacy, and collaborate closely to optimize outcomes.

Panelists discuss how, a collaborative approach to co-managing and co-monitoring patients receiving CAR-TCAR T-cell therapy patients, ensuring continuity of care as they transition to community settings. We They employ detailed care plans, electronic health records integration, and regular follow-ups with community providers to facilitate seamless transitions.

Panelists 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.

Panelists 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.

Panelists 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.

Panelists 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 chimeric antigen receptor (CAR) T-cell therapy in early relapsed multiple myeloma can provide deep and durable responses for eligible patients, though patient selection, timing of referral, manufacturing logistics, and management of adverse effects remain important considerations in optimizing outcomes.

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.

Panelists 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.

Panelists 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).

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.