Publications by authors named "Jean Fontan"

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.

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Background: IMAGE is a retrospective cohort study of patients enrolled in early access programs (EAPs) in France with relapsed/refractory multiple myeloma (RRMM) receiving isatuximab with pomalidomide and dexamethasone (Isa-Pd).

Methods: Patients aged ≥18 years with RRMM who received ≥1 dose of Isa under the EAPs between July 29, 2019 and August 30, 2020 were included. Effectiveness endpoints included progression-free survival (PFS) and response rates.

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Multiple myeloma is characterized by a huge heterogeneity at the molecular level. The RAS/RAF pathway is the most frequently mutated, in ∼50% of the patients. However, these mutations are frequently subclonal, suggesting a secondary event.

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  • - The phase II trial assessed the effectiveness of the RiBVD treatment (rituximab, bendamustine, velcade, and dexamethasone) in patients over 65 with mantle cell lymphoma (MCL), which resulted in a median progression-free survival of 79 months and overall survival of 111 months.
  • - TP53 mutation status and albumin levels were identified as significant prognostic factors, with TP53 mutations linked to a higher risk of shorter progression-free survival and overall survival in the analyzed patient population.
  • - A scoring system combining TP53 mutation status and albumin levels allowed differentiation of patient outcomes, indicating varying survival rates based on the presence of these factors, thus enhancing prognostic assessments
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Combining drugs could be an effective option for treating multirefractory ITP, that is, patients not responding to rituximab, thrombopoietin receptor agonists (TPO-RA) and splenectomy. We conducted a retrospective, multicenter, observational study including multirefractory ITP patients who received a combination of a TPO-RA and an immunosuppressive drug. We included 39 patients (67% women, median age 59 years [range 21-96]), with a median ITP duration of 57 months [3-393] and a median platelet count at initiation of 10 × 10 /L [1-35].

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  • Familial forms of monoclonal gammopathy, including multiple myeloma (MM) and Monoclonal Gammopathy of Undetermined Significance (MGUS), are rare, with MGUS being more commonly observed and sometimes advancing to MM.
  • A study identified 318 families with multiple cases of monoclonal gammopathy, highlighting potential genetic links and family clusters with parent-child and sibling cases.
  • Despite some genetic similarities, familial cases generally present similarly to sporadic cases but show a better prognosis, with longer median survival rates for those with familial MM.
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  • Cytogenetic abnormalities are key indicators of prognosis in multiple myeloma, with del(1p32) identified as a significant negative factor after del(17p).
  • In a study of 2,551 newly diagnosed patients, those with del(1p32) had a much shorter overall survival (49 months) compared to those without it (124 months).
  • The impact of del(1p32) is even worse for patients with biallelic deletions, leading to a median overall survival of just 25 months, emphasizing the need for thorough assessment at diagnosis for appropriate treatment strategies.
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  • High-dose melphalan (HDM) combined with bortezomib (Bor-HDM) was tested in a phase 3 trial for patients with multiple myeloma to see if it was more effective than HDM alone.* -
  • The trial included 300 patients, and results showed no significant differences in complete response rates or minimum residual disease rates between the two treatment groups.* -
  • Although progression-free survival was slightly better in the Bor-HDM group (34.0 months) compared to HDM (29.6 months), the overall survival rates and serious adverse events were similar, indicating Bor-HDM did not provide a clear advantage.*
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  • Primary plasma cell leukemia (pPCL) is a rare and aggressive form of multiple myeloma (MM) that hasn't improved with recent treatments and is not well understood at the molecular level.
  • Researchers conducted DNA and RNA sequencing on plasma cells from 90 newly diagnosed pPCL patients, revealing unique genomic traits, particularly a high incidence of the genetic abnormality t(11;14) and other high-risk features.
  • The study also found that pPCL patients with the t(11;14) abnormality had better overall survival rates (39.2 months) compared to those without it (17.9 months) and expressed different levels of specific genes related to the BCL2 family.
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Introduction: Immunocompromised patients are at high-risk for severe influenza and invasive pneumococcal diseases (IPD). Despite the French Public Health Council (FPHC) and the 7th European Conference on Infections in Leukaemia (ECIL7) recommendations, vaccination coverage remains insufficient. This study aimed to estimate the coverage and determinants of influenza, pneumococcal and diphtheria-tetanus-poliomyelitis (dTP) vaccinations in hematological patients underlying chemotherapy.

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Background: CASSIOPEIA part 1 showed superior depth of response and significantly improved progression-free survival with daratumumab, bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) as induction and consolidation in patients with autologous stem-cell transplant (ASCT)-eligible newly diagnosed multiple myeloma. In part 2, we compared daratumumab maintenance versus observation only.

Methods: CASSIOPEIA is a two-part, open-label, randomised, phase 3 trial of patients aged 18-65 years with newly diagnosed multiple myeloma and Eastern Cooperative Oncology Group performance status 0-2, done in 111 European academic and community practice centres.

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Multiple myeloma (MM) is rare in young patients, especially before age 40 years at diagnosis, representing <2% of all patients with MM. Little is known about the disease characteristics and prognosis of these patients. In this study, we examined 214 patients diagnosed with MM at age ≤40 years over 15 years, in the era of modern treatments.

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Immune thrombocytopenia (ITP) is a rare autoimmune-mediated condition characterized by isolated thrombocytopenia (<100 G/L) after exclusion of other causes. Mostly primary, it is associated with hematological malignancy, autoimmune disorders, or infection in 20% of patients. It is exceptionally described in patients with histiocytosis, mostly in children (seven patients in literature).

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The transition to oral therapies in patients with multiple myeloma (MM) offers potential benefits to patients; however, they must self-manage their medication and adherence plays an important role in patient care. It has been shown that patient satisfaction with their medication has a strong positive correlation with adherence in chronic diseases. The aim of this study was to estimate adherence rate of oral antimyeloma therapies and to identify risk factors for medication non-adherence.

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Despite tremendous improvements in the outcome of patients with multiple myeloma in the past decade, high-risk patients have not benefited from the approval of novel drugs. The most important prognostic factor is the loss of parts of the short arm of chromosome 17, known as deletion 17p (del(17p)). A recent publication (on a small number of patients) suggested that these patients are at very high-risk only if del(17p) is associated with TP53 mutations, the so-called "double-hit" population.

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Background: Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma.

Methods: In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma at 111 European sites.

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Purpose: The wide heterogeneity in multiple myeloma (MM) outcome is driven mainly by cytogenetic abnormalities. The current definition of high-risk profile is restrictive and oversimplified. To adapt MM treatment to risk, we need to better define a cytogenetic risk classification.

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Purpose: Carfilzomib is a novel generation proteasome inhibitor. The Carmysap trial demonstrated that twice-weekly KMP (carfilzomib, melphalan, prednisone) might challenge the MPV (melphalan, prednisone, bortezomib) standard. We sought to study KMP weekly, allowing to increase carfilzomib's dose with maintained efficacy and improved safety profile.

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We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for patients with mantle cell lymphoma aged 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of six cycles of treatment at 28-day intervals.

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