Deep-Learning-Based Prediction of t(11;14) in Multiple Myeloma H&E-Stained Samples.

Background: Translocation of chromosomes 11 and 14 [t(11;14)(q13;32)] is the most common primary translocation in multiple myeloma (MM). Patients harboring t(11;14) exhibit high response rates to BCL-2 inhibitors, underscoring the importance of rapid detection to guide treatment decisions. While fluorescence in situ hybridization (FISH) remains the gold standard for detecting this abnormality, its application is limited by challenges related to speed, accessibility, and cost.

Clinical outcomes in older adults treated outside clinical studies: highlighting the octogenarian experience.

With an aging population, multiple myeloma (MM) increasingly affects octogenarians (Octos; age of ≥80 years), yet data on their management and outcomes, particularly if treated outside clinical trials, remain limited. This retrospective study analyzed 652 patients aged ≥70 years, diagnosed with active MM between 2014 and 2023, identified in the Maccabi Healthcare Services medical records. Patient characteristics, treatment, time to next treatment (TTNT), overall survival (OS), and factors influencing outcomes, were compared between Octo and older adults (OL) aged 70 to <80 years.

Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial.

Frontline daratumumab-based triplet and quadruplet standard-of-care regimens have demonstrated improved survival outcomes in newly diagnosed multiple myeloma (NDMM). For patients with transplant-ineligible NDMM, triplet therapy with either daratumumab plus lenalidomide and dexamethasone (D-Rd) or bortezomib, lenalidomide and dexamethasone (VRd) is the current standard of care. This phase 3 trial evaluated subcutaneous daratumumab plus VRd (D-VRd) in patients with transplant-ineligible NDMM or for whom transplant was not planned as the initial therapy (transplant deferred).

Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma.

Background: Talquetamab (anti-G protein-coupled receptor family C group 5 member D) and teclistamab (anti-B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class-exposed relapsed or refractory multiple myeloma.

Methods: We conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study.

Efficacy and safety of daratumumab in intermediate/high-risk smoldering multiple myeloma: final analysis of CENTAURUS.

Early intervention in smoldering multiple myeloma (SMM) may delay progression to MM. Here, we present the final analysis of the phase 2 CENTAURUS study. In total, 123 patients with intermediate/high-risk SMM were randomized to IV daratumumab 16 mg/kg after 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.

The Outcome of Octogenarian Patients with Multiple Myeloma Treated Outside Clinical Studies, Focusing on Tolerability and Efficacy of Treatment.

Data on the outcome of octogenarian multiple myeloma (MM) patients (pts), especially if treated outside clinical studies, are scanty. : MM pts ≥ 80 years, treated at TASMC with first-line therapy between 2010 and 2023, were reviewed. Characteristics and outcomes were analyzed.

Nivolumab, Pomalidomide, and Elotuzumab Combination Regimens for Treatment of Relapsed and Refractory Multiple Myeloma: Results from the Phase 3 CheckMate 602 Study.

Background: Preclinical studies suggest that combining nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor, with pomalidomide/dexamethasone (Pd) with or without elotuzumab, an antisignaling lymphocytic activation molecule F7 monoclonal antibody, may improve multiple myeloma (MM) treatment efficacy.

Patients And Methods: The phase 3 CheckMate 602 study (NCT02726581) assessed the efficacy and safety of nivolumab plus pomalidomide/dexamethasone (NPd) and NPd plus elotuzumab (NE-Pd). Eligible patients (aged ≥ 18 years) had measurable MM after ≥ 2 prior lines of therapy, that included an immunomodulatory drug (IMiD) and proteasome inhibitor (PI), each for ≥ 2 consecutive cycles, alone or combined, and were refractory to their last line of therapy.

Dual anti-viral treatment for persistent COVID-19 in immunocompromised hemato-oncological patients is associated with a favorable prognosis and minor side effects.

In hemato-oncological patients, COVID-19 can present as a persistent infection with ongoing symptoms and viral replication over a prolonged period of time. Data are scarce on the preferred treatment options for these patients. We describe our experience with a five-day course of dual anti-viral treatment with remdesivir and nirmatrelvir/ritonavir for hemato-oncological immunocompromised patients with persistent COVID-19.

Treatment with low-dose, single-agent belantamab mafodotin is safe and provides long-term responses in heavily pretreated multiple myeloma patients.

Objectives: To evaluate whether low-dose belantamab mafodotin (B-MAF) dosing results in lower toxicity and better overall outcome.

Methods: We retrospectively evaluated nine consecutive patients treated with low-dose (1.9 mg/kg) B-MAF.

Management and outcome of 500 multiple myeloma patients treated for first relapse outside clinical studies.

Treatment options for multiple myeloma (MM) at 1st relapse are expanding. The current study compared common 2nd line regimens administered in a real-world setting. MM patients registered in Maccabi health care services and treated with second line therapy during 2014-2020 were evaluated, analyzing factors affecting time to third line therapy (TT3T).

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma.

Background: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease.

Methods: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care.

Preclinical discovery and initial clinical data of WVT078, a BCMA × CD3 bispecific antibody.

B-cell maturation antigen (BCMA) is an ideal target in multiple myeloma (MM) due to highly specific expression in malignant plasma cells. BCMA-directed therapies including antibody drug conjugates, chimeric antigen receptor-T cells and bispecific antibodies (BsAbs) have shown high response rates in MM. WVT078 is an anti-BCMA× anti-CD3 BsAb that binds to BCMA with subnanomolar-affinity.

On the influence of computed tomography's slice thickness on computer tomography based finite element analyses results.

Background: Patient-specific autonomous finite element analyses of femurs, based on clinical computed tomography scans may be used to monitor the progression of bone-related diseases. Some CT scan protocols provide lower resolution (slice thickness of 3 mm) that affects the accuracy. To investigate the impact of low-resolution scans on the CT-based finite element analyses results, identical CT raw data were reconstructed twice to generate a 1 mm ("gold standard") and a 3 mm slice thickness scans.

Real-world experience with belantamab mafodotin therapy for relapsed/refractory multiple myeloma: A multicentre retrospective study.

Belantamab mafodotin, an immuno-conjugate targeting B-cell maturation antigen, showed single-agent activity in phase 1 and 2 studies, and was recently approved for heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients. Real-world data and long-term follow-up are scarce. We conducted a multisite retrospective study aimed to assess safety and efficacy of belantamab mafodotin monotherapy administered via the GSK expanded access compassionate care programme.

Feasibility of a Novel Academic BCMA-CART (HBI0101) for the Treatment of Relapsed and Refractory AL Amyloidosis.

Purpose: AL amyloidosis (AL) treatments are generally based on those employed for multiple myeloma. Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CART)-cell therapy, already approved for multiple myeloma, might be too toxic for patients with AL.

Experimental Design: Here we describe the ex vivo applicability of a novel in-house, academic anti-BCMA CAR construct on AL primary cells, as well as the safety and efficacy in 4 patients with relapsed/refractory (RR) primary AL, treated in a phase I clinical trial (NCT04720313).

Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents.

B-cell maturation antigen (BCMA)-targeting therapies, including bispecific antibodies (BsAbs) and antibody-drug conjugates (ADCs), are promising treatments for multiple myeloma (MM), but disease may progress after their use. CARTITUDE-2 is a phase 2, multicohort study evaluating the safety and efficacy of cilta-cel, an anti-BCMA chimeric antigen receptor T therapy, in various myeloma patient populations. Patients in cohort C progressed despite treatment with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and noncellular anti-BCMA immunotherapy.

Clinical features, therapy patterns, outcomes and prognostic factors of solitary plasmacytomas: a report of the Israeli Myeloma Study Group.

Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia. In this retrospective multicenter study, 68 SP patients were included. Compared to solitary extramedullary plasmacytoma (SEP), patients with solitary bone plasmacytoma (SBP) were younger (57.

REGEN-COV antibody combination in patients with lymphoproliferative malignancies and SARS-CoV-2 infection.

Patients with lymphoproliferative diseases are at high risk for SARS-CoV-2-related complications and mortality. The role of casirivimab and imdevimab (REGEN-COV), a neutralizing antibody cocktail, to treat immunocompromised hemato-oncological patients with SARS-CoV-2 disease 2019 (Covid-19) remains unknown. Here, we present our clinical experience on the outcome of 15 hematological patients treated with REGEN-COV for SARS-CoV-2 infection.

Validation of diffusion MRI as a biomarker for efficacy using randomized phase III trial of bevacizumab with or without VB-111 in recurrent glioblastoma.

Background: Evidence from single and multicenter phase II trials have suggested diffusion MRI is a predictive imaging biomarker for survival benefit in recurrent glioblastoma (rGBM) treated with anti-VEGF therapy. The current study confirms these findings in a large, randomized phase III clinical trial.

Methods: Patients with rGBM were enrolled in a phase III randomized (1:1), controlled trial (NCT02511405) to compare the efficacy and safety of bevacizumab (BV) versus BV in combination with ofranergene obadenovec (BV+VB-111), an anti-cancer viral therapy.