Real-world safety and efficacy of teclistamab in relapsed/refractory multiple myeloma: results from a multicenter, retrospective study and descriptive meta-analysis.

Patients participating in clinical trials are highly selected and may not represent the general population. The pivotal study of teclistamab (MajesTEC-1), a B-cell maturation antigen (BCMA)xCD3 bispecific antibody, demonstrated impressive response rates and progression free survival in relapsed/refractory multiple myeloma (RRMM) with acceptable toxicity. We performed a retrospective study of 58 patients treated as standard of care at four US academic centers to determine how these results translated to the real-world.

Venetoclax in the Treatment of Multiple Myeloma: A Retrospective Analysis of 79 Patients.

Venetoclax, the first-in-class BCL-2 inhibitor, has shown efficacy in multiple myeloma (MM), particularly in patients with the t(11;14) translocation. This single-center retrospective analysis included MM patients treated with venetoclax from November 2017 to March 2023. Data encompassed demographics, disease characteristics, treatment regimens, and outcomes using median progression-free-survival (mPFS).

Comprehensive molecular profiling of multiple myeloma identifies refined copy number and expression subtypes.

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation's Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are the target of recurrent gain-of-function and loss-of-function events.

Post-ASCT consolidation with elotuzumab, lenalidomide, and dexamethasone or elotuzumab, pomalidomide, and dexamethasone in high-risk and ultra-high-risk multiple myeloma: a retrospective single-center study.

Patients with high-risk multiple-myeloma (HRMM) and ultra-high-risk multiple-myeloma (UHRMM) show rapid disease progression and shorter survival compared to those with standard-risk multiple-myeloma (SRMM). Lenalidomide maintenance after autologous stem cell transplant (ASCT) has shown inferior outcomes in this subgroup compared to SRMM, and there is an unmet need for improved post-ASCT therapy. This retrospective study, from September 2016 to March 2023, assesses elotuzumab combined with lenalidomide or pomalidomide and dexamethasone (ERd or EPd) as consolidation therapy post-ASCT for HRMM and UHRMM patients.

Outcomes of Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma Receiving Salvage Cytotoxic Therapy with Supportive Stem Cell Boost.

Background: Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the neoplastic proliferation of plasma cells, which produce monoclonal immunoglobulin that can cause vital organ damage, subsequently leading to significant morbidity and mortality. Autologous hematopoietic stem cell transplant (ASCT) is the standard-of-care management of eligible patients with newly diagnosed MM. Experts recommend collecting enough stem cells upfront to support a possible tandem transplant, salvage ASCT, or a stem cell "boost" to allow for the administration of multiagent cytotoxic chemotherapy in patients with relapsed/refractory disease.

Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial.

Idecabtagene vicleucel (ide-cel) is a B-cell-maturation antigen (BCMA)-directed chimeric antigen receptor T cell therapy. We performed a post hoc analysis of a single-arm phase 1 multicenter study in relapsed/refractory multiple myeloma (CRB-401) (n = 62; median follow-up, 18.1 months).

Inhibition of NF-κB DNA Binding Suppresses Myeloma Growth via Intracellular Redox and Tumor Microenvironment Modulation.

Multiple myeloma is a plasma cell malignancy that is still largely incurable, despite considerable progress in recent years. NF-κB is a well-established therapeutic target in multiple myeloma, but none of the currently available treatment options offer direct, specific pharmacologic targeting of NF-κB transcriptional activity. Thus, we designed a novel direct NF-κB inhibitor (IT848) as a drug candidate with strong potential for clinical translation and conducted comprehensive in vitro and in vivo mechanistic studies in multiple myeloma cell lines, primary multiple myeloma cells, xenograft models, and immunocompetent mouse models of multiple myeloma.

Natural killer cells activity against multiple myeloma cells is modulated by osteoblast-induced IL-6 and IL-10 production.

Background: Natural killer (NK) cells are part of the innate arm of the immune system; as such NK cells can be activated rapidly to target virus-infected cells and tumor cells without prior sensitization. The human NK-92MI cell line is among the most widely used NK cell in preclinical research studies and has also been approved for clinical applications. Previous studies have shown that osteoblasts (OSB) confer drug resistance in multiple myeloma (MM) and other cancers that metastasize to the bone marrow.

Patient-reported outcomes following autologous stem cell transplant for patients with multiple myeloma.

We evaluated changes in patient-reported outcomes and cognitive function from pre- to 3-6 months post-treatment among 42 newly diagnosed patients with multiple myeloma undergoing transplant with complete data using PROMIS-29. There were statistically significant improvements in physical ( < .001) and mental health ( < .

Preferences and Priorities for Relapsed Multiple Myeloma Treatments Among Patients and Caregivers in the United States.

Introduction/background: This study aimed to describe patient and caregiver preferences for treatments of relapsed or refractory multiple myeloma (MM).

Materials And Methods: A survey including discrete-choice experiment (DCE) and best-worst scaling (BWS) exercises was conducted among US patients with relapsed or refractory MM and their caregivers. The DCE included six attributes with varying levels including progression-free survival (PFS), toxicity, and mode and frequency of administration.

Sustained Hematopoietic Engraftment Potential after Prolonged Storage of Cryopreserved Hematopoietic Stem Cells Used in Salvage Autologous Stem Cell Transplantation.

Salvage autologous hematopoietic stem cell transplantation (HSCT) is an effective treatment for patients with relapsed multiple myeloma (MM). Peripheral blood stem cells (PBSCs), a source of hematopoietic stem cells (HSCs), are collected before the first transplantation, and adequate quantities of PBSCs can be collected and stored potentially for years to support at least 2 transplantations for eligible patients. To ensure the safety of salvage HSCT in the treatment of patients in subsequent relapse, PBSCs must retain the potential to engraft even after several years of cryopreservation.

Pomalidomide, dexamethasone, and daratumumab immediately after lenalidomide-based treatment in patients with multiple myeloma: updated efficacy, safety, and health-related quality of life results from the phase 2 MM-014 trial.

Patients with relapsed/refractory multiple myeloma (RRMM) need proven subsequent therapies after early-line lenalidomide treatment failure. The phase 2 MM-014 trial (NCT01946477) investigated pomalidomide, dexamethasone, and daratumumab after 1 to 2 prior treatment lines (62.5%, 1 prior line) in patients with RRMM and prior lenalidomide (75.

Indatuximab ravtansine plus dexamethasone with lenalidomide or pomalidomide in relapsed or refractory multiple myeloma: a multicentre, phase 1/2a study.

Background: Indatuximab ravtansine (BT062) is an antibody-drug conjugate that binds to CD138 and synergistically enhances the antitumor activity of lenalidomide in preclinical models of multiple myeloma. This phase 1/2a study was done to determine the safety, activity, and pharmacokinetics of indatuximab ravtansine in combination with immunomodulatory drugs in patients with relapsed or refractory multiple myeloma.

Methods: This open-label, phase 1/2a study took place at nine hospital sites in the USA.

KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma.

Patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed (to an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody) have limited treatment options and there is no standard of care. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, demonstrated efficacy in triple-class exposed RRMM patients in the KarMMa trial (NCT03361748). In this retrospective study (KarMMa-RW), patient-level data from triple-class exposed RRMM patients were merged into a single data model and compared with KarMMa using trimmed stabilized inverse probability of treatment weighting.

Phase 1b trial of isatuximab, an anti-CD38 monoclonal antibody, in combination with carfilzomib as treatment of relapsed/refractory multiple myeloma.

Background: Isatuximab (Isa), an anti-CD38 monoclonal antibody, and carfilzomib (K), a next-generation proteasome inhibitor (PI), both have potent single-agent activity in relapsed and refractory multiple myeloma (RRMM).

Methods: This phase 1b study evaluated the combination of Isa and K in 33 patients with RRMM. Isa was administered by intravenous infusion in 3 dosing cohorts: dose level 1 (Isa at 10 mg/kg biweekly), dose level 2 (DL2; Isa at 10 mg/kg weekly for 4 doses and then biweekly), and dose level 3 (Isa at 20 mg/kg weekly for 4 doses and then biweekly) and all patients received K (20 mg/m intravenously for cycle 1, days 1 and 2, and then 27 mg/m for all subsequent doses).

Associations Between Amplification (1q) and Prior Cancer in a Real-World De Novo Myeloma Cohort.

Genomic biomarkers inform treatment in multiple myeloma (MM), making patient clinical data a potential window into MM biology. We evaluated de novo MM patients for associations between specific MM cytogenetic patterns and prior cancer history. Analyzing a MM real-world dataset, we identified a cohort of 1769 patients with fluorescent in situ hybridization cytogenetic testing at diagnosis.

Prevalence and Survival Impact of Self-Reported Symptom and Psychological Distress Among Patients With Multiple Myeloma.

Background: Advances in the management of multiple myeloma (MM) have extended survival and reduced painful skeletal-related events. As MM is evolving toward a chronic disease, we sought to determine the prevalence of self-reported symptom burden and psychological distress, and to determine the association of distress with survival.

Methods: The CPASS-7 patient-reported outcome instrument was administered to a convenience sample of MM patients at 7 outpatient cancer centers.

A phase 1b study of once-weekly carfilzomib combined with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma.

Twice-weekly carfilzomib with lenalidomide-dexamethasone (Rd) is an effective regimen for newly diagnosed multiple myeloma (NDMM). Here we evaluated once-weekly carfilzomib with Rd (once-weekly KRd) in NDMM patients. The NDMM patients were enrolled regardless of transplant eligibility.

Immunomodulation in Pomalidomide, Dexamethasone, and Daratumumab-Treated Patients with Relapsed/Refractory Multiple Myeloma.

Purpose: Addition of daratumumab to pomalidomide and low-dose dexamethasone (LoDEX) is a safe and effective combination for relapsed/refractory multiple myeloma treatment. We sought to better understand immune combinational benefit of pomalidomide and daratumumab with LoDEX.

Patients And Methods: Immunophenotypic changes were analyzed in peripheral blood from longitudinal sampling of patients treated with this triplet regimen from cohort B of the CC4047-MM-014 phase II trial (NCT01946477).

Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study.

Background: Tocilizumab, a monoclonal antibody directed against the interleukin-6 receptor, has been proposed to mitigate the cytokine storm syndrome associated with severe COVID-19. We aimed to investigate the association between tocilizumab exposure and hospital-related mortality among patients requiring intensive care unit (ICU) support for COVID-19.

Methods: We did a retrospective observational cohort study at 13 hospitals within the Hackensack Meridian Health network (NJ, USA).