Ajai Chari, MD

Dr. Ajai Chari and NP Samantha Shenoy discuss practical considerations for long-term management of newly diagnosed multiple myeloma (NDMM), focusing on treatment duration, ongoing therapy, and patient-centered care. The faculty explore the rationale for continuous treatment approaches and how response depth, including minimal residual disease (MRD) negativity, may continue to evolve with extended therapy. The conversation emphasizes that treatment duration decisions should be individualized based on tolerability, patient preferences, comorbidities, and long-term management goals. Dr. Chari and NP Shenoy also review real-world follow-up strategies, highlighting the importance of multidisciplinary collaboration, symptom management, patient education, and shared decision-making throughout the treatment journey. Practical insights are provided regarding the role of advanced practice providers in supporting adherence, monitoring treatment-related toxicities, and helping patients navigate prolonged therapy while maintaining quality of life and optimizing clinical outcomes in NDMM.

Dr. Ajai Chari and NP Samantha Shenoy review the CEPHEUS trial and discuss its contribution to the evolving frontline treatment landscape in newly diagnosed multiple myeloma (NDMM). The faculty summarize the study design and examine the rationale for incorporating daratumumab into a quadruplet regimen for patients without planned upfront transplant. The discussion focuses on the achievement of deeper responses and higher rates of minimal residual disease (MRD) negativity observed with the daratumumab-containing regimen, as well as the clinical relevance of sustained MRD negativity and response depth over time. Dr. Chari and NP Shenoy explore how MRD assessment may provide additional insight into long-term disease control and discuss the potential implications of these findings for treatment duration and future management strategies. The conversation emphasizes interpretation of emerging data while considering how evolving evidence may influence clinical decision-making in patients with NDMM.

Dr. Ajai Chari and Dr. Rahul Banerjee review the clinical development of talquetamab in relapsed/refractory multiple myeloma (RRMM), focusing on key findings from the MonumenTAL-1 study and the evolution of GPRC5D-directed therapy.

Dr. Ajai Chari and Dr. Rahul Banerjee discuss the growing need for therapeutic targets beyond BCMA in relapsed/refractory multiple myeloma (RRMM) and examine the rationale for GPRC5D-directed therapies.

Dr. Ajai Chari and NP Samantha Shenoy examine the long-term efficacy outcomes from the MAIA trial and discuss the clinical significance of response depth in newly diagnosed multiple myeloma (NDMM). The faculty review progression-free survival improvements, increasing rates of complete response, and the achievement of minimal residual disease (MRD) negativity with daratumumab-based therapy compared with the control regimen. The conversation focuses on how responses may continue to deepen with ongoing treatment and explores the relationship between MRD negativity, durable disease control, and long-term patient outcomes. Dr. Chari and NP Shenoy also discuss the evolving role of MRD assessment as a tool for evaluating treatment effectiveness and highlight how long-term follow-up data can inform clinical decision-making regarding continued therapy. The discussion emphasizes practical interpretation of the MAIA findings and their relevance to contemporary frontline management strategies for patients with NDMM.

Dr. Ajai Chari and NP Samantha Shenoy review the design and long-term follow-up results of the MAIA trial and discuss their clinical implications for the management of newly diagnosed multiple myeloma (NDMM) in transplant-ineligible patients. The faculty examine key efficacy outcomes, including progression-free survival, overall survival, and minimal residual disease (MRD) negativity, while highlighting the continued deepening of responses observed with ongoing daratumumab-based therapy. Dr. Chari and NP Shenoy discuss the relevance of continuous treatment until disease progression, the durability of clinical benefit demonstrated with extended follow-up, and the applicability of the MAIA patient population to everyday clinical practice. The conversation also addresses safety and tolerability considerations associated with long-term treatment and explores how these findings have influenced frontline treatment decisions and expectations for sustained disease control in patients with NDMM.

New trials show BCMA bispecifics and CAR‑T boost survival in early relapsed, high‑risk myeloma, outperforming Dara-based triplets.

Experts unpack how frontline CD38 quadruplets reshape relapse strategy and high‑risk definitions, spotlighting talquetamab’s promise in myeloma.

Dr. Ajai Chari and NP Samantha Shenoy discuss the clinical rationale for incorporating daratumumab-based regimens into the frontline management of newly diagnosed multiple myeloma (NDMM). The conversation explores the biologic rationale for targeting CD38 and reviews how daratumumab-based combinations have contributed to deeper responses and improved minimal residual disease (MRD) negativity in clinical studies. The faculty discuss patient selection in transplant-ineligible disease, emphasizing the importance of balancing efficacy with tolerability, comorbidities, and long-term treatment goals. Dr. Chari and NP Shenoy also share their perspectives on how CD38-directed therapy has influenced frontline treatment strategies and discuss practical considerations when selecting regimens for older or medically complex patients. The discussion provides important clinical context for understanding the evidence supporting daratumumab-based approaches and their role in optimizing outcomes for patients with NDMM.

Dr. Ajai Chari and NP Samantha Shenoy introduce the program by reviewing the evolving treatment landscape in newly diagnosed multiple myeloma (NDMM) and discussing the factors that influence contemporary frontline treatment decisions. The faculty highlight the shift toward individualized treatment selection based on patient fitness, frailty, comorbidities, and treatment goals rather than transplant eligibility alone. They explore the growing incorporation of CD38-targeted therapies into frontline treatment strategies, the increasing emphasis on achieving deep and durable responses, and the importance of long-term disease control. Dr. Chari and NP Shenoy also discuss the expanding role of quadruplet regimens, minimal residual disease (MRD) assessment, and treatment duration considerations as part of modern NDMM management. The conversation establishes the clinical context for the subsequent review of MAIA and CEPHEUS trial data and their implications for everyday practice.

Panelists discuss how patients relapsing shortly after BCMA CAR T-cell therapy should receive GPRC5D-targeted bispecifics rather than repeat BCMA therapies, given the evidence that prior BCMA exposure reduces efficacy of subsequent BCMA-directed treatments.

Panelists discuss how a triple class–exposed patient with comorbidities like COPD represents an ideal candidate for BCMA-directed bispecific therapy over CAR T-cell therapy due to the ability to titrate dosing and manage respiratory infection risks.

Panelists discuss how community practices need clear protocols for after-hours fever management, adequate caregiver support assessment, and standardized algorithms for cytokine release syndrome treatment across multiple bispecific products.

Panelists discuss how step-up dosing has successfully transitioned from inpatient-only to hybrid and outpatient models using prophylactic tocilizumab and standardized protocols for managing cytokine release syndrome.

Panelists discuss how talquetamab’s unique skin and taste toxicities are manageable through dose modifications and supportive care, with IVIG prophylaxis being crucial for BCMA-targeted but not necessarily GPRC5D-targeted therapies.

Panelists discuss how real-world data consistently show bispecific efficacy matching clinical trial results despite treating higher-risk patients, and how prophylactic interventions have reduced cytokine release syndrome severity.

Panelists discuss how CAR T-cell therapy should generally precede bispecifics when possible due to T-cell exhaustion concerns, though they agree there are virtually no absolute contraindications to bispecific therapy.

Panelists discuss how bispecifics are reversing the historical paradigm of diminishing returns in relapsed/refractory multiple myeloma, achieving 60% to 70% response rates lasting over a year in heavily pretreated patients.

Panelists discuss how patient preferences for treatment-free intervals are increasingly important in therapy selection, with bispecifics offering potential for response-adapted dosing and early discontinuation while maintaining remissions.

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.