Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone Induction in Newly Diagnosed Myeloma: Analysis of the MIDAS Trial.

In patients with transplant-eligible newly diagnosed multiple myeloma, induction therapy with a quadruplet regimen prior to autologous transplant is the standard of care. The phase III IFM2020-02-MIDAS study (NCT04934475) assessed a minimal residual disease (MRD)-driven consolidation and maintenance strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD). Here, we report safety and efficacy outcomes of six 28-day cycles of IsaKRD.

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.

Early systemic insults following severe sepsis-associated encephalopathy of critically ill patients: association with mortality and awakening-an analysis of the OUTCOMEREA database.

Background: Sepsis-associated encephalopathy (SAE) may be worsened by early systemic insults. We aimed to investigate the association of early systemic insults with outcomes of critically ill patients with severe SAE.

Methods: We performed a retrospective analysis using data from the French OUTCOMEREA prospective multicenter database.

Evolution of frontline treatment for multiple myeloma: clinical investigation of quadruplets containing carfilzomib and anti-CD38 monoclonal antibodies.

Although survival rates for patients with newly diagnosed multiple myeloma (NDMM) have improved over recent decades, multiple myeloma (MM) remains without a cure for most. There is increasing consensus that achievement of deep remissions, especially minimal residual disease negativity (MRD -), in frontline treatment is crucial and translates into improved survival. The standard of care (SOC) for NDMM consists at minimum of a triplet regimen of therapies, with or without an autologous stem cell transplant, or a doublet regimen for certain ineligible, particularly frail patients who may have specific limitations.

Efficacy and Safety of Daratumumab in Intermediate/High-risk Smoldering Multiple Myeloma: Final Analysis of CENTAURUS.

Early intervention of smoldering multiple myeloma (SMM) may delay progression to multiple myeloma. Here, we present the final analysis of the phase 2 CENTAURUS study (NCT02316106). In total, 123 patients with intermediate/high-risk SMM were randomized to intravenous daratumumab 16 mg/kg following a Long intense (n = 41), Intermediate (n = 41), or Short intense (n = 41) dosing schedule.

Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma.

Background: Daratumumab, an anti-CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma. Data are needed regarding the use of daratumumab for high-risk smoldering multiple myeloma, a precursor disease of active multiple myeloma for which no treatments have been approved.

Methods: In this phase 3 trial, we randomly assigned patients with high-risk smoldering multiple myeloma to receive either subcutaneous daratumumab monotherapy or active monitoring.

LocoMMotion: a study of real-life current standards of care in triple-class exposed patients with relapsed/refractory multiple myeloma - 2-year follow-up (final analysis).

Treatment of relapsed/refractory multiple myeloma (RRMM) is challenging as patients exhaust all available therapies and the disease becomes refractory to standard drug classes. Here we report the final results of LocoMMotion, the first prospective study of real-world clinical practice (RWCP) in triple-class exposed (TCE) patients with RRMM, with a median follow-up of 26.4 months (range, 0.

Isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple myeloma (IKEMA): overall survival analysis of a phase 3, randomised, controlled trial.

Background: Isatuximab is an anti-CD38 monoclonal antibody approved for the treatment of relapsed or refractory multiple myeloma. Previous analyses of the IKEMA trial showed prolonged progression-free survival in patients with this disease who received isatuximab in combination with carfilzomib-dexamethasone as compared with those who received carfilzomib-dexamethasone alone. Herein, we report the analysis of overall survival from the IKEMA trial.

Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial.

Background: CASSIOPEIA part 1 demonstrated superior depth of response and prolonged progression-free survival with daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) alone as an induction and consolidation regimen in transplant-eligible patients newly diagnosed with myeloma. In CASSIOPEIA part 2, daratumumab maintenance significantly improved progression-free survival and increased minimal residual disease (MRD)-negativity rates versus observation. Here, we report long-term study outcomes of CASSIOPEIA.

Ixazomib plus daratumumab and dexamethasone: Final analysis of a phase 2 study among patients with relapsed/refractory multiple myeloma.

Novel therapies have improved outcomes for multiple myeloma (MM) patients, but most ultimately relapse, making treatment decisions for relapsed/refractory MM (RRMM) patients increasingly challenging. We report the final analysis of a single-arm, phase 2 study evaluating the oral proteasome inhibitor (PI) ixazomib combined with daratumumab and dexamethasone (IDd; NCT03439293). Sixty-one RRMM patients (ixazomib/daratumumab-naïve; 1-3 prior therapies) were enrolled to receive IDd (28-day cycles) until disease progression/unacceptable toxicity.

Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma.

Background: Bortezomib, lenalidomide, and dexamethasone (VRd) is a preferred first-line treatment option for patients with newly diagnosed multiple myeloma. Whether the addition of the anti-CD38 monoclonal antibody isatuximab to the VRd regimen would reduce the risk of disease progression or death among patients ineligible to undergo transplantation is unclear.

Methods: In an international, open-label, phase 3 trial, we randomly assigned, in a 3:2 ratio, patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation to receive either isatuximab plus VRd or VRd alone.

Impact of prior treatment on selinexor, bortezomib, dexamethasone outcomes in patients with relapsed/refractory multiple myeloma: Extended follow-up subgroup analysis of the BOSTON trial.

Objectives: To analyze the impact of prior therapies on outcomes with selinexor, bortezomib, and dexamethasone (SVd) versus bortezomib and dexamethasone (Vd) in 402 patients with relapsed/refractory multiple myeloma (RRMM) in the phase 3 BOSTON trial.

Methods: Post hoc analysis of progression-free survival (PFS), overall survival (OS), and safety for lenalidomide-refractory, proteasome inhibitor (PI)-naïve, bortezomib-naïve, and one prior line of therapy (1LOT) patient subgroups.

Results: At a median follow-up of over 28 months, clinically meaningful improvements in PFS were noted across all groups with SVd.

Correlation of immune fitness with response to teclistamab in relapsed/refractory multiple myeloma in the MajesTEC-1 study.

Teclistamab, an off-the-shelf B-cell maturation antigen (BCMA) × CD3 bispecific antibody that mediates T-cell activation and subsequent lysis of BCMA-expressing myeloma cells, is approved for the treatment of patients with relapsed/refractory multiple myeloma (R/RMM). As a T-cell redirection therapy, clinical outcomes with teclistamab may be influenced by patient immune fitness and tumor antigen expression. We correlated tumor characteristics and baseline immune profiles with clinical response and disease burden in patients with R/RMM from the pivotal phase 1/2 MajesTEC-1 study, focusing on patients treated with 1.

An IL-1β-driven neutrophil-stromal cell axis fosters a BAFF-rich protumor microenvironment in individuals with multiple myeloma.

Human bone marrow permanently harbors high numbers of neutrophils, and a tumor-supportive bias of these cells could significantly impact bone marrow-confined malignancies. In individuals with multiple myeloma, the bone marrow is characterized by inflammatory stromal cells with the potential to influence neutrophils. We investigated myeloma-associated alterations in human marrow neutrophils and the impact of stromal inflammation on neutrophil function.

Mechanisms of resistance to bispecific T-cell engagers in multiple myeloma and their clinical implications.

Bispecific T-cell engagers (TCEs) are revolutionizing patient care in multiple myeloma (MM). These monoclonal antibodies, that redirect T cells against cancer cells, are now approved for the treatment of triple-class exposed relapsed/refractory MM (RRMM). They are currently tested in earlier lines of the disease, including in first line.

Isatuximab in combination with carfilzomib and dexamethasone in 1q21+ patients with relapsed/refractory multiple myeloma: Long-term outcomes in the Phase 3 IKEMA study.

Gain/amplification of 1q21 (≥3 copies), a chromosomal abnormality frequently observed in multiple myeloma, can negatively affect prognosis, due to its involvement in resistance to anti-myeloma therapy and disease progression. In this updated subgroup analysis of the randomized, Phase 3 IKEMA study (NCT03275285) in relapsed/refractory multiple myeloma (RRMM), we evaluated progression-free survival (PFS) and depth of response with the anti-CD38 antibody isatuximab plus carfilzomib-dexamethasone (Isa-Kd) versus Kd, in 1q21+ patients and related subgroups, at long-term follow-up (44.2 months).