T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies.
View Article and Find Full Text PDFAmong patients with poly-refractory myeloma, autologous chimeric antigen receptor T-cell therapy offers exceptional promise. With the availability of bispecific antibodies, a total immunotherapeutic strategy in combination with chimeric antigen receptor T-cell therapy is now feasible. See related article by Fandrei et al.
View Article and Find Full Text PDFIntroduction: Several frailty assessment tools exist for classifying older adults with multiple myeloma (MM) by their frailty status, such as the International Myeloma Working Group (IMWG) frailty score and the simplified frailty scale. The level of agreement between the IMWG frailty score and the simplified frailty scale remains unknown.
Materials And Methods: In a cross-sectional analysis of a prospective cohort study, we identified adults ≥50y initiating a new treatment regimen for MM who underwent a baseline geriatric assessment (GA).
Increasing number of older adults with Plasma Cell Disorders (PCDs) are receiving autologous stem cell transplant (ASCT) in the US. Hospital associated disability (HAD) is a common complication associated with acute care hospitalization among older adults. To estimate the prevalence and prognostic significance of HAD among older adults with MM undergoing ASCT.
View Article and Find Full Text PDFBackground: Obesity is an established modifiable risk factor for multiple myeloma (MM). However, associations of obesity and MM risk in Black populations, for whom obesity and MM are more common, is less clear.
Methods: Using participants enrolled in the Integrative Molecular And Genetic Epidemiology study, we evaluated the association of anthropometric traits with MM risk overall, stratified by race and sex.
Introduction: Health outcome preferences of older adults with cancer vary based on burden/intensity of treatment and its impact on health outcomes such as survival, quality of life, and functional and cognitive well-being. We studied the association between age and health outcome preferences of adults with multiple myeloma (MM).
Materials And Methods: Using a single center prospective cohort study, we identified adults ≥50y with MM who underwent geriatric assessment (GA) within 30 days of initiating a new line of therapy.
In the MASTER study (NCT03224507), daratumumab+carfilzomib/lenalidomide/dexamethasone (D-KRd) demonstrated promising efficacy in transplant-eligible newly diagnosed multiple myeloma (NDMM). In GRIFFIN (NCT02874742), daratumumab+lenalidomide/bortezomib/dexamethasone (D-RVd) improved outcomes for transplant-eligible NDMM. Here, we present a post hoc analysis of patients with high-risk cytogenetic abnormalities (HRCAs; del[17p], t[4;14], t[14;16], t[14;20], or gain/amp[1q21]).
View Article and Find Full Text PDFThe combination of anti-CD38 monoclonal antibodies to a proteasome inhibitor, an immunomodulatory agent and dexamethasone (quadruplet-QUAD) in sequence with autologous stem cell transplantation (ASCT) leads to deep and durable responses in newly diagnosed multiple myeloma (NDMM). Disease progression in the first year post-QUADs is uncommon. We analysed 274 consecutive NDMM patients treated with QUADs + ASCT.
View Article and Find Full Text PDFBr J Haematol
February 2024
Autologous patient-derived adoptive T-cell therapies have revolutionized the management of relapsed multiple myeloma (MM). However, the current manufacturing and quality control processes result in lengthy vein-to-vein time, making bridging therapy necessary for most patients. Yet the decision and choice of optimal bridging therapy are complex in the heavily pretreated relapsed MM patient.
View Article and Find Full Text PDFBackground: For patients with newly diagnosed multiple myeloma, reaching minimal residual disease (MRD) negativity after treatment is associated with improved outcomes; however, the use of MRD to modulate therapy remains elusive. We present the final analysis of the MASTER trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd) therapy in patients with newly diagnosed multiple myeloma, in which MRD status is used to modulate treatment duration and cessation.
Methods: MASTER was a multicentre, single-arm, phase 2 trial conducted in five academic medical centres in the USA.
Robust anti-myeloma activity with teclistamab in patients with severe renal impairment.
View Article and Find Full Text PDFQuadruplet induction, autologous hematopoietic cell transplant (AHCT), and measurable residual disease (MRD) response-adapted consolidation yield an unprecedented depth of response in newly diagnosed multiple myeloma. Patients treated on MASTER (NCT03224507) ceased therapy and entered active surveillance (MRD-SURE) after achieving MRD negativity. This study characterizes quantitative changes in the immunoglobulin (Ig) gene repertoire by next-generation sequencing and serum gamma globulin levels.
View Article and Find Full Text PDFFor eligible patients with newly diagnosed multiple myeloma (NDMM), standard of care includes induction therapy followed by autologous stem cell transplantation (ASCT). Daratumumab as monotherapy and in combination treatment is approved across multiple lines of therapy for multiple myeloma (MM), and lenalidomide is an effective and commonly used agent for induction and maintenance therapy in MM. However, there is concern that lenalidomide and daratumumab given as induction therapy might impair mobilization of stem cells for ASCT.
View Article and Find Full Text PDFMultiple myeloma is a complex hematological malignancy with substantial heterogeneity in its clinical manifestations, biological processes, and patient outcomes. Although many biomarkers with have been identified to assist with disease monitoring and prognostication, predictive markers that inform treatment decisions remain elusive. As treatments become more effective, assays for measurable residual disease (MRD) below the level of detection of traditional assays have emerged as an essential component of disease assessment with powerful prognostic value for dynamic risk assessment.
View Article and Find Full Text PDFBackground: Patients with Diffuse Large Bcell Lymphoma (DLBCL) with MYC and BCL2 and/or BCL6 gene rearrangements [double-hit lymphoma/triple-hit lymphoma (DHL/THL)] have poor prognosis in the relapsed/refractory setting.
Methods: We utilized a real-world deidentified database of DLBCL patients and report patterns of therapy utilization in relapsed/refractory DLBCL. We used log-rank test to compare real-world overall survival (rwOS) among DHL and non-DHL subgroups for CAR Tcell therapy or ASCT respectively, stratified for prior lines of therapy.
The incremental impact of autologous hematopoietic cell transplantation (AHCT) on disease burden with quadruplet induction in newly diagnosed multiple myeloma (NDDM) can be reappraised with the serial assessment of minimal residual disease (MRD). We describe the impact of AHCT on MM burden assessed by next-generation sequencing (NGS) for patients enrolled in a clinical trial utilizing quadruplet induction, AHCT, followed by MRD-adapted consolidation. We describe quantitative changes in MRD burden with AHCT and explore patient and disease features influencing the magnitude of MRD reduction with AHCT.
View Article and Find Full Text PDFAssociation of immunoglobulin isotypes with survival in the context of modern prognostic factors has not been determined. We utilized the Flatiron Health Electronic Health Record database and identified 8468 MM patients. Compared to IgG MM, patients with IgA MM were more likely to have ISS-III, anemia, and t(4;14), and light chain (LC) MM had higher renal dysfunction and t(11;14).
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