Nursing Considerations for the Clinical Management of Adverse Events Associated with Talquetamab in Patients with Relapsed or Refractory Multiple Myeloma.

OBJECTIVES: Talquetamab is a newly approved bispecific antibody targeting the CD3 receptor on T cells and a receptor, G protein-coupled receptor family C group 5 member D (GPRC5D), highly expressed on multiple myeloma (MM) cells. In addition to immune therapy-related adverse events (AEs) associated with bispecific antibody therapies, talquetamab is associated with unique skin/nail and oral GPRC5D-related side effects that require additional supportive care. This review provides clinical management strategies for talquetamab based on oncology nurses' experience during the MonumenTAL-1 (NCT03399799/NCT04634552) clinical trial. The objective of this review is to raise awareness among nurses and patients to better understand and manage the side effects associated with talquetamab treatment in order to optimize patient outcomes. DATA SOURCES: MonumenTAL-1 is a phase 1/2 clinical trial of talquetamab in patients with relapsed/refractory MM who are triple-class exposed. Details on overall response, safety, and AE incidence and occurrence were previously published. Management strategies for the T-cell-related and unique GPRC5D-related AEs were collected from oncology nurses from different study sites. CONCLUSION: Talquetamab has shown overall response rates of >71% in patients with relapsed/refractory MM in the MonumenTAL-1 study. AEs were low grade and predictable; few led to study discontinuation. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses have specialized knowledge of treatment administration monitoring based on their participation in the MonumenTAL-1 trial. This review provides information for nurses in both the academic and community settings on how to monitor, counsel, and support patients, which will in turn improve patients' quality of life and overall survival.

Hip microinstability and its association with femoroacetabular impingement: A scoping review.

Introduction: Hip microinstability has become a recognized cause of non-arthritic hip pain and disability in young patients. However, its pathophysiology remains unclear. We want to (1) present an overview of the evidence of hip microinstability and of its association with femoroacetabular impingement (FAI), (2) map out the type of evidence available, and (3) make recommendations for future research. Methods: A deductive analysis and extraction method was used to extract information. In addition, diagnostic accuracy statistics were extracted or calculated. Results: Of the 2,808 identified records, 123 were eligible for inclusion. Different definitions for microinstability exist. A standardized terminology and clear diagnostic criteria are lacking. FAI and microinstability may be associated and may aggravate each other. Conservative treatment strategies for FAI and microinstability are similar. The reported prevalence of microinstability in combination with FAI ranges from 21% to 42% in adults undergoing hip arthroscopy or magnetic resonance arthrography (MRA) of the hip. Conclusion: Hip microinstability and FAI may be associated, occur together, or exacerbate each other. To better address this topic, a standardized terminology for microinstability is essential. Achieving consensus on physical examination and diagnosis is also necessary. Initial efforts to establish uniform diagnostic criteria have been made, but further work is needed. Specifically, randomized controlled trials are required to evaluate the effectiveness of training programmes aimed at reducing symptoms in individuals with microinstability, with or without FAI. Such studies will enable clinicians to manage microinstability with greater confidence within this context.

Clinical Management of Patients With Relapsed/Refractory Multiple Myeloma Treated With Talquetamab.

BACKGROUND: Talquetamab is a bispecific antibody targeting the multiple myeloma-associated antigen G protein-coupled receptor family C group 5 member D (GPRC5D). In the phase 1/2 MonumenTAL-1 trial (NCT03399799/NCT04634552), overall responses rates were > 71% in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM). Due to the distribution of the target antigen, a unique pattern of GPRC5D-associated adverse events (AEs) was observed, together with T-cell redirection-associated AEs. Management strategies for talquetamab-associated AEs are described. DISCUSSION: GPRC5D-associated AEs included dermatologic (rash, nonrash, and nail toxicities) and oral AEs (dysgeusia, dysphagia, and dry mouth). The incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were consistent with other T-cell redirection therapies. The incidence of high-grade infections was lower than observed with B-cell maturation antigen-targeting bispecific antibodies, with less frequent use of intravenous immunoglobulin required. GPRC5D-associated AEs were mostly low grade and led to few discontinuations. Skin toxicities were managed with emollients, topical corticosteroids, and oral corticosteroids (for high-grade, persistent, or AEs that progress). Nail toxicities were commonly managed with emollients. Based on investigator experience, dose modification may be effective for controlling oral events. Observation for potential weight changes is required. Infections were managed per standard of care. CRS and ICANS were effectively managed, consistent with other trials of T-cell redirection therapies. CONCLUSION: Although talquetamab had a distinct safety profile, AEs were considered clinically manageable and mostly low grade. With appropriate education and support, health care practitioners can ensure patients with RRMM maintain quality of life and treatment adherence.

GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review.

Multiple myeloma is a genetically complex and heterogenous malignancy with a 5-year survival rate of approximately 60%. Despite advances in therapy, patients experience cycles of remission and relapse, with each successive line of therapy associated with poorer outcomes; therefore, therapies with different mechanisms of action against new myeloma antigens are needed. G protein-coupled receptor class C group 5 member D (GPRC5D) has emerged as a novel therapeutic target for the treatment of multiple myeloma. We review the biology and target validation of GPRC5D, and clinical data from early phase trials of GPRC5D-targeting bispecific antibodies, talquetamab and forimtamig, and chimeric antigen receptor T cell (CAR-T) therapies, MCARH109, OriCAR-017, and BMS-986393. In addition to adverse events (AEs) associated with T-cell-redirection therapies irrespective of target, a consistent pattern of dermatologic and oral AEs has been reported across several trials of GPRC5D-targeting bispecific antibodies, as well as rare cerebellar events with CAR-T therapy. Additional studies are needed to understand the underlying mechanisms involved in the development of skin- and oral-related toxicities. We review the strategies that have been used to manage these GPRC5D-related toxicities. Preliminary efficacy data showed overall response rates for GPRC5D-targeting T-cell-redirecting therapies were ≥64%; most responders achieved a very good partial response or better. Pharmacokinetics/pharmacodynamics showed that these therapies led to cytokine release and T-cell activation. In conclusion, results from early phase trials of GPRC5D-targeting T-cell-redirecting agents have shown promising efficacy and manageable safety profiles, including lower infection rates compared with B-cell maturation antigen- and Fc receptor-like protein 5-targeting bispecific antibodies. Further clinical trials, including those investigating GPRC5D-targeting T-cell-redirecting agents in combination with other anti-myeloma therapies and with different treatment modalities, may help to elucidate the future optimal treatment regimen and sequence for patients with multiple myeloma and improve survival outcomes. Video Summary.

Comparative Efficacy of Talquetamab vs. Current Treatments in the LocoMMotion and MoMMent Studies in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma.

INTRODUCTION: Talquetamab, a bispecific antibody targeting GPRC5D × CD3, is approved for the treatment of patients with triple-class -exposed (TCE) relapsed/refractory multiple myeloma (RRMM) on the basis of the results from the phase I/II MonumenTAL-1 trial. The relative effectiveness of talquetamab vs. real-world physician's choice of therapy (RWPC) was assessed using adjusted comparisons. METHODS: An external control arm for MonumenTAL-1 (subcutaneously administered talquetamab 0.4 mg/kg weekly [QW] and 0.8 mg/kg every other week [Q2W]) was created from two observational real-world studies: LocoMMotion and MoMMent. Imbalances in baseline covariates were adjusted using inverse probability weighting. The relative effectiveness of talquetamab vs. RWPC was estimated for overall response rate (ORR), ≥ very good partial response (VGPR), and ≥ complete response (CR); odds ratios and relative response ratios (RRs) were derived from weighted logistic regression. Hazard ratios (HRs) for duration of response (DOR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were estimated using a weighted Cox proportional hazards model. RESULTS: After reweighting, baseline characteristics were balanced across cohorts. In adjusted comparisons, patients treated with talquetamab QW (n = 143) had significantly improved outcomes vs. RWPC; RRs were ORR 2.67, p < 0.0001; ≥ VGPR 4.70, p < 0.0001; ≥ CR 78.05, p = 0.0002; and HRs were PFS 0.52, p < 0.0001; TTNT 0.48, p < 0.0001; OS 0.36, p < 0.0001. Patients treated with talquetamab Q2W (n = 145) also had significantly improved outcomes vs. RWPC; RRs were ORR 2.62, p < 0.0001; ≥ VGPR 5.04, p < 0.0001; ≥ CR 101.14, p = 0.0002; and HRs were PFS 0.40, p < 0.0001; TTNT 0.39, p < 0.0001; OS 0.37, p < 0.0001. CONCLUSION: Effectiveness of talquetamab for both schedules was significantly better than RWPC for ORR, ≥ VGPR, ≥ CR, PFS, OS, and TTNT, highlighting its clinical benefit for patients with TCE RRMM. TRIAL REGISTRATION: MonumenTAL-1, ClinicalTrials.gov identifier NCT03399799/NCT04634552; LocoMMotion, ClinicalTrials.gov identifier NCT04035226; MoMMent, ClinicalTrials.gov identifier NCT05160584.