Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance.

Purpose: Early treatment of high-risk smoldering myeloma has been shown to delay progression to multiple myeloma (MM). We conducted this trial with curative intention using a treatment approach employed for newly diagnosed patients with MM.

Methods: Patients with high-risk smoldering myeloma (>50% progression risk at 2 years) and transplant candidates were included and received induction therapy with carfilzomib, lenalidomide, and dexamethasone (KRd), six cycles, followed by high-dose melphalan (200 mg/m) autologous stem-cell transplantation (HDM-ASCT), two KRd consolidation cycles, and Rd maintenance for 2 years.

Single-point and kinetics of peripheral residual disease by mass spectrometry to predict outcome in patients with high-risk smoldering multiple myeloma included in the GEM-CESAR trial.

The value of quantitative immunoprecipitation mass spectrometry (QIP-MS) to identify the M-protein is being investigated in patients with monoclonal gammopathies but no data are yet available in high-risk smoldering myeloma (HRsMM). We have, therefore, investigated QIP-MS to monitor peripheral residual disease (PRD) in 62 HRsMM patients enrolled in the GEM-CESAR trial. After 24 cycles of maintenance, detecting the M-protein by MS or clonal plasma cells by next-generation flow cytometry (NGF) identified cases with a significantly shorter median progression-free survival (mPFS) (MS: not reached vs.

Randomized phase II study of weekly carfilzomib 70 mg/m and dexamethasone with or without cyclophosphamide in relapsed and/or refractory multiple myeloma patients.

In this randomized phase II study (GEM-KyCyDex, clinicaltrials gov. Identifier: NCT03336073), the combination of weekly carfilzomib 70 mg/m2, cyclophosphamide and dexamethasone (KCd) was compared to carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines (PL). One hundred and ninety-seven patients were included and randomized 1:1 to receive KCd (97 patients) or Kd (100 patients) in 28-day cycles until progressive disease or unacceptable toxicity occurred.

A simple score to predict early severe infections in patients with newly diagnosed multiple myeloma.

Infections remain a common complication in patients with multiple myeloma (MM) and are associated with morbidity and mortality. A risk score to predict the probability of early severe infection could help to identify the patients that would benefit from preventive measures. We undertook a post hoc analysis of infections in four clinical trials from the Spanish Myeloma Group, involving a total of 1347 patients (847 transplant candidates).

Recovery of polyclonal immunoglobulins during treatment in patients ineligible for autologous stem-cell transplantation is a prognostic marker of longer progression-free survival and overall survival.

Immunoparesis is the suppression of normal polyclonal immunoglobulins and is present in most patients with newly diagnosed multiple myeloma (MM). The association of immunoparesis at diagnosis, and particularly its recovery along with treatment, with survival in patients ineligible for autologous stem-cell transplantation (ASCT) has not been well established. This retrospective study evaluated the impact of immunoparesis in 431 patients diagnosed with MM, ineligible for ASCT, with a median overall survival of 36 months [95% confidence interval (CI): 31-40].

B-Cell Regeneration Profile and Minimal Residual Disease Status in Bone Marrow of Treated Multiple Myeloma Patients.

B-cell regeneration during therapy has been considered as a strong prognostic factor in multiple myeloma (MM). However, the effects of therapy and hemodilution in bone marrow (BM) B-cell recovery have not been systematically evaluated during follow-up. MM (n = 177) and adult (≥50y) healthy donor (HD; n = 14) BM samples were studied by next-generation flow (NGF) to simultaneously assess measurable residual disease (MRD) and residual normal B-cell populations.

Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group.

This phase I/II trial evaluated the combination of the kinesin spindle protein inhibitor filanesib with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma (RRMM) patients. Forty-seven RRMM patients with a median of three prior lines (2-8) and 94% refractory to lenalidomide were included: 14 in phase I and 33 in phase II. The recommended dose was 1·25 mg/m of filanesib on days 1, 2, 15, 16, with pomalidomide 4 mg on days 1-21 and dexamethasone 40 mg weekly.

Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy.

Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival.

Unraveling the heterogeneity of IgM monoclonal gammopathies: a gene mutational and gene expression study.

Immunoglobulin M (IgM) monoclonal gammopathies show considerable variability, involving three different stages of presentation: IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), asymptomatic Waldenström's macroglobulinemia (AWM), and symptomatic WM (SWM). Despite recent findings about the genomic and transcriptomic characteristics of such disorders, we know little about the causes of this clinical heterogeneity or the mechanisms involved in the progression from indolent to symptomatic forms. To clarify these matters, we have performed a gene expression and mutational study in a well-characterized cohort of 69 patients, distinguishing between the three disease presentations in an attempt to establish the relationship with the clinical and biological features of the patients.