We report on the use of a daratumumab-CHOP regimen for treatment of gamma heavy chain disease (γHCD) in a 79-year-old woman. γHCD is a very rare hematological disease, often associated with an underlying lymphoproliferative disorder. Only a few cases are reported in the literature, and, therefore, strong evidence is lacking regarding new therapeutic strategies.
View Article and Find Full Text PDFBackground: Measurable residual disease (MRD) is a major prognostic factor in newly diagnosed multiple myeloma. An assessment of an MRD-guided consolidation strategy in patients who are eligible for autologous stem-cell transplantation (ASCT) may be useful.
Methods: In this phase 3 trial, we randomly assigned transplantation-eligible patients with newly diagnosed myeloma who had completed induction therapy with isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) to receive consolidation therapy according to their MRD status.
Human parainfluenza virus type 3 (HPIV-3) can be responsible for mild to severe respiratory infections and hospital epidemics. We investigated an outbreak in a hematology unit. Respiratory viruses were screened using multiplex PCR.
View Article and Find Full Text PDFMultiple myeloma (MM) is the 2 most common haematological malignancy in France, and its treatment has been improved in recent years by the arrival of new therapies such as CAR-T cells and bispecific antibodies. Among the latter, teclistamab, indicated as a 4-line treatment for relapsed or refractory MM patients, targets the CD3 antigen on the surface of T lymphocytes and the BCMA antigen on the surface of malignant plasma cells. The adverse reactions to teclistamab described in the summary of product characteristics (SPC) mention hypogammaglobulinemia, leading to recurrent infections.
View Article and Find Full Text PDFObjectives: This final post hoc analysis evaluated patient-reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5-month follow-up in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.
Methods: Key scales from the EORTC QLQ-C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed.
For patients with transplant-eligible newly diagnosed multiple myeloma, induction therapy with a quadruplet regimen before autologous transplant is the standard of care. The phase 3 IFM2020-02-MRD-adapted strategy (MIDAS) study assessed a minimal residual disease (MRD)-driven consolidation and maintenance strategy after induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD). We report safety and efficacy outcomes of six 28-day cycles of IsaKRD in 791 patients.
View Article and Find Full Text PDFThe risk of T cell malignancies after chimeric antigen receptor (CAR) T cell therapy is a concern, although the true incidence remains unclear. Here we analyzed the DESCAR-T registry database, encompassing all pediatric and adult patients with hematologic malignancies who received CAR T cell therapy in France since 1 July 2018. Of the 3,066 patients included (2,536 B cell lymphoma, 162 B cell acute lymphoblastic leukemia (ALL) and 368 multiple myeloma), 1,680 (54.
View Article and Find Full Text PDFKidney disease is a common complication of monoclonal immunoglobulin (MIg)-secreting B-cell disorders and predominantly occurs in patients who do not meet the criteria for an overt hematological disease. To distinguish this situation from monoclonal gammopathy of undetermined significance, which lacks organ damage, the term monoclonal gammopathy of renal significance (MGRS) was introduced to depict the association of a small, otherwise indolent B-cell clone, with renal disease induced by the secreted MIg. The spectrum of renal disorders in MGRS is wide, encompassing both tubular and glomerular disorders, classified according to the composition of deposits and their ultrastructural pattern of organization.
View Article and Find Full Text PDFInflammatory form of Waldenström macroglobulinemia (iWM) predicts outcomes after immuno-chemotherapy and Bruton tyrosine kinase inhibitors, but its origin is unknown. Here, we unravel increased clonal hematopoiesis in patients with iWM (61% vs 23% in noninflammatory WM), suggesting a contribution of environmental cells to iWM.
View Article and Find Full Text PDFOutcomes are poor in triple-class-exposed (TCE) relapsed and refractory multiple myeloma (R/RMM). In the phase 3 KarMMa-3 trial, patients with TCE R/RMM and 2 to 4 prior regimens were randomized 2:1 to idecabtagene vicleucel (ide-cel) or standard regimens (SRs). An interim analysis (IA) demonstrated significantly longer median progression-free survival (PFS; primary end point; 13.
View Article and Find Full Text PDFRev Med Interne
December 2024
Seric hyperviscosity syndrome is a medical emergency linked to hyperproteinemia. The clinical diagnosis hinges on a triad of symptoms: mucosal hemorrhages, visual disturbances, and neurological disorders, observed in the most severe cases. Diagnosis is swiftly confirmed through an urgent fundoscopic examination.
View Article and Find Full Text PDFA second autologous stem-cell transplantation (ASCT2) is considered for relapsed multiple myeloma (RMM) patients showing prolonged response after a first ASCT. However, given breakthrough treatments like anti-CD38 and immunotherapy, its role remains debated. We conducted a real-life study in 10 French centers (1996-2017) involving 267 RMM patients receiving ASCT2.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFNephrol Dial Transplant
November 2024
Background: Carfilzomib, a new proteasome inhibitor indicated for patients with relapsed/refractory myeloma, has been associated with cases of thrombotic microangiopathy (CFZ-TMA). The role of variants in the complement alternative pathway and therapeutic potential of complement blockade with eculizumab remain to be determined.
Methods: We report 37 cases of CFZ-TMA recorded in the French reference center for TMA with their clinical characteristics, genetic analysis and outcome according to treatments.
Mechanisms underlying the disruption of self-tolerance in acquired autoimmunity remain unclear. Immunoglobulin A (IgA) nephropathy is an acquired autoimmune disease where deglycosylated IgA1 (IgA subclass 1) auto-antigens are recognized by IgG auto-antibodies, forming immune complexes that are deposited in the kidneys, leading to glomerulonephritis. In the intestinal microbiota of patients with IgA nephropathy, there was increased relative abundance of mucin-degrading bacteria, including .
View Article and Find Full Text PDFBackground: Chimeric antigen receptor T-cell therapy idecabtagene vicleucel (ide-cel) showed significantly improved progression-free survival compared with standard regimens in adults with relapsed and refractory multiple myeloma who had received two to four previous regimens in the ongoing phase 3 KarMMa-3 trial (NCT03651128). This study analysed patient-reported outcomes (PROs), a KarMMa-3 secondary endpoint.
Methods: In the randomised, open-label, phase 3 KarMMa-3 trial, 386 patients in hospitals (≥18 years of age, with measurable disease and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who had received two to four previous regimens-including an immunomodulatory agent, a proteasome inhibitor, and daratumumab-and had documented disease progression after receiving their last dose of the last therapy) were randomly assigned to ide-cel (n=254) or standard regimens (daratumumab, pomalidomide, and dexamethasone; daratumumab, bortezomib, and dexamethasone; ixazomib, lenalidomide, and dexamethasone; carfilzomib and dexamethasone; or elotuzumab, pomalidomide, and dexamethasone; n=132).
Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma targeting B-cell maturation antigen (BCMA) induces high overall response rates. However, relapse still occurs and novel strategies for targeting multiple myeloma cells using CAR T-cell therapy are needed. SLAMF7 (also known as CS1) and CD38 on tumor plasma cells represent potential alternative targets for CAR T-cell therapy in multiple myeloma, but their expression on activated T cells and other hematopoietic cells raises concerns about the efficacy and safety of such treatments.
View Article and Find Full Text PDF