A model for predicting day-100 stem cell transplant-related mortality in AL amyloidosis.

Autologous stem cell Transplant (ASCT)-related mortality (TRM) in AL amyloidosis remains elevated. AL amyloidosis patients (n = 1718) from 9 centers, transplanted 2003-2020 were included. Pre-ASCT variables of interest were assessed for association with day-100 all-cause mortality.

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.

Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial.

Background: In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes.

Methods: In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 10 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone).

Belantamab Mafodotin in Relapsed/Refractory AL Amyloidosis: Real-World Multi-Center Experience and Review of the Literature.

Introduction: Treatment for relapsed/refractory AL amyloidosis (AL) is an unmet need. The safety and efficacy of belantamab mafodotin (BLM) in multiple myeloma are known, whereas in AL data are limited.

Methods: We report a multi-center cohort of AL patients receiving BLM, and review all previous data on BLM therapy in AL.

Amyloid Typing in Cardiac Amyloidosis Using Western Blotting.

Background: Cardiac amyloidosis (CA) is characterized by the extracellular deposition of misfolded protein in the heart. Precise identification of the amyloid type is often challenging, but critical, since the treatment and prognosis depend on the disease form and the type of deposited amyloid. Coexistence of clinical conditions such as old age, monoclonal gammopathy, chronic inflammation, or peripheral neuropathy in a patient with cardiomyopathy creates a differential diagnosis between the major types of CA: amyloidosis light chains (AL), amyloidosis transthyretin (ATTR) and amyloidosis A (AA).

Amino acid sequence homology of monoclonal serum free light chain dimers and tissue deposited light chains in AL amyloidosis: a pilot study.

Objectives: Diagnosis of light chain amyloidosis (AL) requires demonstration of amyloid deposits in a tissue biopsy followed by appropriate typing. Previous studies demonstrated increased dimerization of monoclonal serum free light chains (FLCs) as a pathological feature of AL. To further examine the pathogenicity of FLC, we aimed at testing amino acid sequence homology between circulating and deposited light chains (LCs).

Anti-RBD IgG antibodies and neutralizing antibody levels after the second BNT162b2 dose in patients with plasma cell disorders.

Patients with plasma cell disorders (PCD) are at an increased risk for severe morbidity and mortality due to COVID-19. Recent data have suggested that patients with hematological malignancies, including those with PCD, have suboptimal antibody response to COVID-19 vaccination. We compared the antibody titers of 213 patients with PCD to those of 213 immunocompetent healthcare workers after the second vaccine dose of the BNT162b2 mRNA vaccine.

Venetoclax in Relapse/Refractory AL Amyloidosis-A Multicenter International Retrospective Real-World Study.

Therapeutic options in relapsed refractory (R/R) light-chain (AL) amyloidosis patients are limited. Given the encouraging results in t(11;14) multiple myeloma and the high prevalence of t(11;14) in AL amyloidosis, venetoclax is an attractive treatment option in this setting. We report here the results of a multi-center retrospective study on 26 R/R AL amyloidosis patients treated off-label with venetoclax.

Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma.

Multiple myeloma (MM) is a plasma cell malignancy that is accompanied by hypercalcemia, renal failure, anemia, and lytic bone lesions. Heparanase (HPSE) plays an important role in supporting and promoting myeloma progression, maintenance of plasma cell stemness, and resistance to therapy. Previous studies identified functional single nucleotide polymorphisms (SNPs) located in the HPSE gene.

CXCL13 chemokine is a novel player in multiple myeloma osteolytic microenvironment, M2 macrophage polarization, and tumor progression.

Background: We assessed the mechanism by which multiple myeloma (MM) shapes the bone marrow (BM) microenvironment and affects MΦ polarization.

Methods: In vivo xenograft model of BM-disseminated human myeloma, as well as analysis of MM cell lines, stromal components, and primary samples from patients with MM, was utilized.

Results: Analysis of the BM from MM-bearing mice inoculated with human CXCR4-expressing RPMI8226 cells revealed a significant increase in M2 MΦ cell numbers (p < 0.

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.

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.

Addition of elotuzumab to lenalidomide and dexamethasone for patients with newly diagnosed, transplantation ineligible multiple myeloma (ELOQUENT-1): an open-label, multicentre, randomised, phase 3 trial.

Background: Elotuzumab plus lenalidomide and dexamethasone has shown improved progression-free and overall survival versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. We aimed to assess these regimens in patients with newly diagnosed multiple myeloma who are ineligible for haematopoietic stem-cell transplantation (HSCT).

Methods: ELOQUENT-1 is an open-label, multicentre, randomised, phase 3 trial conducted at 185 hospitals, oncology practices, and research centres in 19 countries.

Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma.

In the primary analysis of the phase III COLUMBA study, daratumumab by subcutaneous administration (DARA SC) demonstrated non-inferiority to intravenous administration (DARA IV) for relapsed or refractory multiple myeloma (RRMM). Here, we report the final analysis of efficacy and safety from COLUMBA after a median of 29.3 months follow-up (additional 21.

Diagnosis and management of multiple myeloma during pregnancy: case report, review of the literature, and an update on current treatments.

The simultaneous occurrence of pregnancy and multiple myeloma (MM) is rare. The challenge of diagnosing MM during pregnancy is demonstrated in the case presented here. Despite the rarity of concurrent MM and pregnancy, this possibility should be considered in patients with signs and symptoms that may be attributed to MM so as not to delay the diagnosis and decision about pregnancy continuation and initiation of an appropriate and safe therapy to the mother and fetus.

BNT162b2 mRNA COVID-19 vaccination in immunocompromised patients: A prospective cohort study.

Background: Trials of the Pfizer-BioNTech BNT162b2 mRNA vaccine showed 95% efficacy in preventing symptomatic disease; however, the trials excluded immunocompromised patients (ICPs). We aim at analyzing antibody response in ICPs.

Methods: A prospective cohort study was conducted at Sheba Medical Center, Israel, between January and April 2020, in 1274 participants who received the vaccine, including 1002 ICPs and 272 immunocompetent healthcare workers (HCWs).

Long-acting granulocyte colony-stimulating factor pegfilgrastim (lipegfilgrastim) for stem cell mobilization in multiple myeloma patients undergoing autologous stem cell transplantation.

Autologous stem cell transplantation (ASCT) is a standard of care in newly-diagnosed multiple myeloma (MM) patients. Several studies before the introduction of novel therapies in MM, demonstrated a pegylated G-CSF to be successful in mobilizing peripheral blood stem cells (PBSCs). Lipegfilgrastim is a novel long-acting G-CSF that is produced by the conjugation of a single 20-kDa polyethelene glycol to the natural O-glycosylation site of G-CSF.

Blocking of Transient Receptor Potential Vanilloid 1 (TRPV1) promotes terminal mitophagy in multiple myeloma, disturbing calcium homeostasis and targeting ubiquitin pathway and bortezomib-induced unfolded protein response.

Background: Chemoresistance remains a major treatment obstacle in multiple myeloma (MM). Novel new therapies are thus in need. Transient Receptor Potential Vanilloid type 1 (TRPV1) is a calcium-permeable ion channel that has been demonstrated to be expressed in solid tumors.

Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy (PLEIADES): an open-label Phase II study.

Daratumumab is a CD38-targeting monoclonal antibody approved for intravenous (IV) infusion for multiple myeloma (MM). We describe the Phase II PLEIADES study of a subcutaneous formulation of daratumumab (DARA SC) in combination with standard-of-care regimens: DARA SC plus bortezomib/lenalidomide/dexamethasone (D-VRd) for transplant-eligible newly diagnosed MM (NDMM); DARA SC plus bortezomib/melphalan/prednisone (D-VMP) for transplant-ineligible NDMM; and DARA SC plus lenalidomide/dexamethasone (D-Rd) for relapsed/refractory MM. In total, 199 patients were treated (D-VRd, n = 67; D-VMP, n = 67; D-Rd, n = 65).

Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX.

High cytogenetic risk abnormalities confer poor outcomes in multiple myeloma patients. In POLLUX, daratumumab/lenalidomide/dexamethasone (D-Rd) demonstrated significant clinical benefit versus lenalidomide/dexamethasone (Rd) in relapsed/refractory multiple myeloma (RRMM) patients. We report an updated subgroup analysis of POLLUX based on cytogenetic risk.

Daratumumab for relapsed AL amyloidosis-When cumulative real-world data precedes clinical trials: A multisite study and systematic literature review.

Objectives: Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab treatment in RRAL in real-world setting.

Methods: A retrospective multisite study of RRAL patients treated with daratumumab alone and in combinations.

Elotuzumab, lenalidomide, and dexamethasone in RRMM: final overall survival results from the phase 3 randomized ELOQUENT-2 study.

Prolonging overall survival (OS) remains an unmet need in relapsed or refractory multiple myeloma (RRMM). In ELOQUENT-2 (NCT01239797), elotuzumab plus lenalidomide/dexamethasone (ERd) significantly improved progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd) in patients with RRMM and 1-3 prior lines of therapy (LoTs). We report results from the pre-planned final OS analysis after a minimum follow-up of 70.