Impact of Extraosseous Extramedullary Disease on Outcomes of Patients with Relapsed-Refractory Multiple Myeloma receiving Standard-of-Care Chimeric Antigen Receptor T-Cell Therapy.

The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the outcomes of RRMM patients who were treated with standard-of-care (SOC) chimeric antigen receptor (CAR) T-cell therapy and had active extraosseous EMD before the infusion. Data were retrospectively collected from patients at three US institutions with the intent to receive SOC CAR T. Responses were assessed per the International Myeloma Working Group criteria. A total of 152 patients proceeded with infusion, of whom 47 (31%) had EMD (EMD group) and 105 (69%) did not (non-EMD group). Baseline patient characteristics were comparable between the two groups. The EMD group had a higher incidence of high-grade CRS, steroid and anakinra use, and thrombocytopenia on day +30 compared to the non-EMD group. In addition, the EMD group had an inferior overall response rate (58% vs 96%, p < 0.00001), median progression-free survival (PFS) (5.1 vs 12.4 months; p < 0.0001), and overall survival (OS) (12.2 vs 27.5 months; p = 0.00058) compared to the non-EMD group. We further subdivided the non-EMD patients into those with paramedullary disease (PMD-only group, n = 26 [17%]) and those with neither EMD nor PMD (bone marrow-contained group or BM-only group, n = 79 [52%]). Patients with PMD-only had similar median PFS (11.2 vs 13.6 months, p = 0.3798) and OS (not reached [NR] vs 27.5 months, p = 0.6446) compared to patients with BM-only disease. However, patients with EMD exhibited inferior median PFS (5.1 vs 13.6 months, p < 0.0001) and OS (12.2 vs 27.5, p = 0.0008) compared to patients in the BM-only group. Treatment with SOC CAR T yielded meaningful clinical outcomes in real-world RRMM patients with extraosseous EMD, though responses and survival outcomes were suboptimal compared to patients without EMD. The presence of only EMD but not PMD was associated with significantly worse survival outcomes following the CAR T infusion.

Evaluating ChatGPT as an educational resource for patients with multiple myeloma: A preliminary investigation.

The findings of this study highlight a 95% accuracy rate in ChatGPT responses, as assessed by five myeloma specialists, underscoring its potential as a reliable educational tool.

Management of Adverse Reactions for BCMA-Directed Therapy in Relapsed Multiple Myeloma: A Focused Review.

Anti-B-cell maturation antigen therapies consisting of bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T cells have shown promising results in relapsed refractory multiple myeloma (RRMM). However, the severe side effects include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia(s), infections, hemophagocytic lymphohistiocytosis, and organ toxicity, which could sometimes be life-threatening. This review focuses on these most common complications post-BCMA therapy. We discussed the risk factors, pathogenesis, clinical features associated with these complications, and how to prevent and treat them. We included four original studies for this focused review. All four agents (idecabtagene vicleucel, ciltacabtagene autoleucel, teclistamab, belantamab mafodotin) have received FDA approval for adult RRMM patients. We went through the FDA access data packages of the approved agents to outline stepwise management of the complications for better patient outcomes.

JADPRO Live 2022: Reaching the Peak of Practice.

This special issue of JADPRO includes summaries of select educational sessions presented at JADPRO Live 2022.

Biomarker Pursuit: Keeping Current With Novel Biomarkers in Hematology/Oncology.

In the popular biomarker-focused session at JADPRO Live 2022, presenters paired biomarkers with tumor types for which their expression is most commonly used to determine targeted therapy, identified key assays used to measure common biomarkers, and reviewed recommendations and guidelines for biomarker testing.

Management of Relapsed-Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice.

Multiple myeloma (MM) is the second most common hematologic malignancy in adults worldwide. Over the past few years, major therapeutic advances have improved progression-free and overall survival, as well as quality of life. Despite this recent progress, MM remains incurable in the vast majority of cases. Patients eventually relapse and become refractory to multiple drug classes, making long-term management challenging. In this review, we will focus on the treatment paradigm of relapsed/refractory MM (RRMM) in the era of advanced therapies emphasizing the available novel modalities that have recently been incorporated into routine practice, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and other promising approaches. We will also discuss major factors that influence the selection of appropriate drug combinations or cellular therapies, such as relapse characteristics, and other disease and patient related parameters. Our goal is to provide insight into the currently available and experimental therapies for RRMM in an effort to guide the therapeutic decision-making process.

A Focus on Special Populations in Relapsed Multiple Myeloma.

The overall care of patients with multiple myeloma can present similar challenges. However, disparities in health care require that providers consider each individual's unique circumstances. Disparities based on ethnic/racial group, religion, socioeconomic status, age, sexual orientation or gender identity, or other characteristics can lead to patients receiving less than optimal care and therefore poorer outcomes. Patients who have received more than two lines of therapy can acquire new genetic changes, accelerated cadence of relapse, and suffer from disease sequelae such as pain from prior or ongoing skeletal fractures, recurrent infections, and progressive decline in organ function. Numerous treatment options remain for patients in their first three relapses. Well-designed clinical trials with newer drugs are preferred. Clinicians should discuss clinical trial options and availability with all patients in spite of disparities that may exist. Patients facing disparities are at risk for suboptimal care and should be closely monitored and provided appropriate resources. Continued attention to disease and organ surveillance are critical throughout the course of the disease.

A Focus on Relapsed Multiple Myeloma.

Multiple myeloma (MM) is a relapsing disease for many patients with multiple myeloma. At relapse, patients have many options for treatment once disease has progressed. Advanced practitioners are well suited to set expectations for ongoing therapy and underscore the importance of continued disease monitoring. Criteria for relapsed myeloma rely on biomarker and radiologic imaging, as well as physical exam and awareness of new bone pain or changes in physiologic function. The treatment of patients with relapsed MM requires a personalized approach and considers patient desires in regard to aggressiveness of therapy and willingness to participate in a clinical trial. The prognosis of patients with relapsed MM depends upon disease characteristics at baseline or throughout, as patients may acquire adverse cytogenetic abnormalities through various lines of treatment. Empowering patients to understand their diagnosis, interpret labs, and take an active role in treatment selection through shared decision-making can improve patients' quality of life and enhance adherence.

A Focus on Newly Diagnosed Multiple Myeloma.

Multiple myeloma (MM) is an incurable plasma cell disorder that affects nearly 35,000 people annually. Over 149,000 individuals are estimated to live in the United States with MM. Research has generated a greater understanding of the pathology of this disease, now combined with mature clinical trial data that support the use of combination therapy in treatment. This article focuses on updated diagnosis, prognosis, and treatment of newly diagnosed patients. While the diagnosis of MM remains based on the 2014 International Myeloma Working Group (IMWG) guidelines, we review these and updated recommendations for the diagnosis and treatment of myeloma as well as relevant supportive care. The prognosis of patients with newly diagnosed MM relies heavily on the cytogenetic profile of the disease, along with other patient-specific risk factors. There are multiple first-line treatment options that combine three or four novel agents with the goal of reducing plasma cell burden and achieving minimal residual disease (MRD) negative status early in the treatment trajectory. Supportive care interventions aimed at minimizing the risk of infection and thromboembolic events, and protecting bone health are critical for maintaining quality of life and are as important as therapeutic treatment interventions.

A Focus on CAR T-Cell Therapy and Bispecific Antibodies in Multiple Myeloma.

Significant strides have been made in the management of patients living with myeloma. However, patients with multiply relapsed or refractory multiple myeloma (MM) have a shorter overall survival; therefore, new treatments with novel mechanisms of action are needed in this patient population. Patients with relapsing disease require a full restaging workup, including whole body imaging to evaluate for extramedullary disease and lytic bone lesions, as well as bone marrow biopsy with fluorescence in situ hybridization to determine if the patient has any new chromosomal changes that are present. Therapies utilizing the patient's immune cells, in particular T cells, provide a new option in relapsed/refractory myeloma. Treatment utilizing chimeric antigen receptor (CAR) T cells and/or bispecific antibody therapy provide excellent response rates. As such, advanced practitioners need to be aware of the potential toxicities associated with these newer treatments and how to manage them. This article will focus on the management of patients with relapsed and/or refractory disease who are undergoing treatment with either CAR T-cell therapy or bispecific T cell engager therapy.