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1.
Br J Haematol ; 202(2): 284-288, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37183377

RESUMO

Myeloproliferative neoplasms in blastic phase (MPN-BP) have a dreadful prognosis. We report the characteristics and outcomes of five MPN-BP patients treated with a never-before-described combination of azacytidine and venetoclax (to control BP transformation), added to ruxolitinib (needed to control constitutional symptoms). Median age was 76 years (range 72-84), and worst performance status was 2. The overall response rate was 80%, and the complete remission rate was 40%. With median follow-up of 10.0 months (range 4.2-13.4), median overall survival was 13.4 months (95% CI 4.2-13.4). We did not detect any unexpected treatment-related toxicity, and quality of life was improved.


Assuntos
Azacitidina , Transtornos Mieloproliferativos , Humanos , Idoso , Idoso de 80 Anos ou mais , Azacitidina/efeitos adversos , Crise Blástica/tratamento farmacológico , Resultado do Tratamento , Qualidade de Vida , Transtornos Mieloproliferativos/tratamento farmacológico
3.
Hum Vaccin Immunother ; 20(1): 2387221, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-39143811

RESUMO

France was the first country to grant Sipavibart (AZD3152, an investigational long-acting monoclonal antibody) as a COVID-19 pre-exposure prophylaxis treatment in immunocompromised individuals in December 2023. The first patients to receive Sipavibart had different profiles, but they were all highly immunocompromised with frequently associated hypogammaglobulinemia and other chronic conditions. No adverse event was reported.


Assuntos
COVID-19 , Hospedeiro Imunocomprometido , Profilaxia Pré-Exposição , Humanos , França , Profilaxia Pré-Exposição/métodos , COVID-19/prevenção & controle , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , SARS-CoV-2/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Tratamento Farmacológico da COVID-19
4.
Nat Med ; 30(8): 2235-2241, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38830994

RESUMO

CD38-targeting immunotherapy is approved in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM) that are transplant ineligible (TI) and is considered the best standard of care (SOC). To improve current SOC, we evaluated the added value of weekly bortezomib (V) to isatuximab plus lenalidomide and dexamethasone (IsaRd versus Isa-VRd). This Intergroupe Francophone of Myeloma phase 3 study randomized 270 patients with NDMM that were TI, aged 65-79 years, to IsaRd versus Isa-VRd arms. The primary endpoint was a minimal residual disease (MRD) negativity rate at 10-5 by next-generation sequencing at 18 months from randomization. Key secondary endpoints included response rates, MRD assessment rates, survival and safety. The 18-month MRD negativity rates at 10-5 were reported in 35 patients (26%, 95% confidence interval (CI) 19-34) in IsaRd versus 71 (53%, 95% CI 44-61) in Isa-VRd (odds ratio for MRD negativity 3.16, 95% CI 1.89-5.28, P < 0.0001). The MRD benefit was consistent across subgroups at 10-5 and 10-6, and was already observed at month 12. The proportion of patients with complete response or better at 18 months was higher with Isa-VRd (58% versus 33%; P < 0.0001), as was the proportion of MRD negativity and complete response or better (37% versus 17%; P = 0.0003). At a median follow-up of 23.5 months, no difference was observed for survival times (immature data). The addition of weekly bortezomib did not significantly affect the relative dose intensity of IsaRd. Isa-VRd significantly increased MRD endpoints, including the 18-month negativity rate at 10-5, the primary endpoint, compared with IsaRd. This study proposes Isa-VRd as a new SOC for patients with NDMM that are TI. ClinicalTrials.gov identifier: NCT04751877 .


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Lenalidomida , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Idoso , Masculino , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasia Residual , Resultado do Tratamento
5.
Clin Case Rep ; 11(5): e7343, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37207087

RESUMO

Key Clinical Message: 18F-FDG PET/CT has clinical relevance in HCL at diagnosis and for the follow-up of patients treated, especially in case of atypical presentations such as bone involvements (which are probably underestimated) and poor bone marrow infiltration. Abstract: Bone lesions are rarely reported in Hairy Cell Leukemia (HCL). We report two BRAFV600E mutated HCL patients presented bone lesions at foreground, poor bone marrow involvement, and the important role 18F-FDG PET/CT played in their management. We discuss the crucial role that 18F-FDG PET/CT could play in HCL routine practice.

6.
Leuk Lymphoma ; 63(3): 518-529, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34672244

RESUMO

Smoldering multiple myeloma (SMM) is a heterogeneous group of asymptomatic plasma cell disorder characterized by the presence of monoclonal protein ≥ 30 g/L and/or 10-60% of bone marrow plasma cells and no evidence of SLiM-CRAB criteria according to the 2014 International Myeloma Working Group (IMWG) recommendations. Once the effort to reclassify SMM with active disease as MM requiring treatment was completed, the need to redefine new high-risk SMM arose. The 20/2/20 and the IMWG risk model with the add-on high-risk cytogenetic abnormalities allow to identify high-risk SMM with 50% risk of progression to MM within 2 years, and therefore might help to propose a better therapeutic approach, either with the goal to « cure ¼ by profoundly debulk the MM with aggressive therapies, or alternatively to restore the immune surveillance like a « delay ¼ strategy with immune-based therapies. The debate is still ongoing but clearly challenges the watch-and-wait standard of care.


Assuntos
Mieloma Múltiplo , Mieloma Múltiplo Latente , Biologia , Progressão da Doença , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/terapia , Fatores de Risco , Mieloma Múltiplo Latente/diagnóstico , Mieloma Múltiplo Latente/etiologia , Mieloma Múltiplo Latente/terapia
7.
Cancers (Basel) ; 13(20)2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34680358

RESUMO

Novel treatments are needed to address the lack of options for patients with relapsed or refractory multiple myeloma. Even though immunotherapy-based treatments have revolutionized the field in recent years, offering new opportunities for patients, there is still no curative therapy. Thus, non-immunologic agents, which have proven effective for decades, are still central to the treatment of multiple myeloma, especially for advanced disease. Building on their efficacy in myeloma, the development of proteasome inhibitors and immunomodulatory drugs has been pursued, and has led to the emergence of a novel generation of agents (e.g., carfilzomib, ixazomib, pomalidomide). The use of alkylating agents is decreasing in most treatment regimens, but melflufen, a peptide-conjugated alkylator with a completely new mechanism of action, offers interesting opportunities. Moreover, with the identification of novel targets, new drug classes have entered the myeloma armamentarium, such as XPO1 inhibitors (selinexor), HDAC inhibitors (panobinostat), and anti-BCL-2 agents (venetoclax). New pathways are still being explored, especially the possibility of a mutation-driven strategy, as biomarkers and targeted treatments are increasing. Though multiple myeloma is still considered incurable, the treatment options are expanding and are progressively becoming more diverse, largely because of the continuous development of non-immunologic agents.

8.
Leuk Lymphoma ; 62(11): 2665-2670, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34085595

RESUMO

Primary or secondary immune deficiency (ID) is a risk factor, although rare, to develop Waldenström macroglobulinemia (WM). We aimed to better understand the incidence of this occurrence in the real-life and the outcome of either entity. We conducted a review of 194 WM in the Poitou-Charentes registry and identified 7 (3.6%) with a prior history of ID. Across the 7 WM with ID, 4 progressed to active WM disease and required treatment for WM with a median time between WM diagnosis and the first treatment of 1.5 years (range 0-3). The median time from ID to WM occurrence was 8 years (1-18). WM could develop from ID, although a rare event. Our first action was to systematically decrease immunosuppression with long-term control of ID. Half of indolent WM remained indolent despite ID and for remaining WM none appeared of poor risk WM.


Assuntos
Síndromes de Imunodeficiência , Linfoma de Células B , Macroglobulinemia de Waldenstrom , Humanos , Incidência , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/epidemiologia
9.
J Clin Med ; 9(11)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158277

RESUMO

The multiple myeloma (MM) non transplant eligible (NTE) population is growing in line with the aging of the population in Western countries. Historically, this population has been known for having a greater risk of treatment related toxicity, and therefore drug development was slow and rather oriented towards the improvement of safety profile than the optimization of disease control. However, NTE MM patients, at least for the fit/non frail patients in recent years, seemed to have benefited more from a less palliative care to improve the depth of response and then prolong survival. NTE MM being a quite heterogeneous population, there are still a number of groups of patients that are in need of more efficient therapy, avoiding unnecessary toxicity, particularly for the frail patients. The use of triplet regimen with a melphalan-prednisone (MP) backbone has long been the standard of care for NTE MM, often dedicated to non-frail patients. New standards of care, triplet, and even quadruplet combinations, are emerging on the basis of the MP backbone but also on the more recently approved lenalidomide-dexamethasone (Rd) backbone. These developments were largely possible in line with the development of antibody-based immunotherapies (IT) in MM. The objective to improve outcomes with an acceptable safety profile will see other key therapeutic developments such as the dropping of dexamethasone early in the disease course or various attempts to allow permanent treatment discontinuation with a prolonged disease control. In that context, it is possible that immunomonitoring, minimal residual disease (MRD), and genomic risk-adaptation will become key elements of the treatment decisions on triplet-based regimens.

10.
Cancers (Basel) ; 12(10)2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33050025

RESUMO

The survival rate of multiple myeloma (MM) patients has drastically increased recently as a result of the wide treatment options now available. Younger patients truly benefit from these innovations as they can support more intensive treatment, such as autologous stem cell transplant or multiple drug association (triplet, quadruplet). The emergence of immunotherapy allowed new combinations principally based on monoclonal anti-CD38 antibodies for these patients. Still, the optimal induction treatment has not been found yet. While consolidation is still debated, maintenance treatment is now well acknowledged to prolong survival. Lenalidomide monotherapy is the only drug approved in that setting, but many innovations are expected. Older patients, now logically named not transplant-eligible, also took advantage of these breakthrough innovations as most of the recent drugs have a more acceptable safety profile than previous cytotoxic agents. For this heterogenous subgroup, geriatric assessment has become an essential tool to identify frail patients and provide tailored strategies. At relapse, options are now numerous, especially for patients who were not treated with lenalidomide, or not refractory at least. Concerning lenalidomide refractory patients, approved combinations are lacking, but many trials are ongoing to fill that space. Moreover, innovative therapeutics are increasingly being developed with modern immunotherapy, such as chimeric antigen receptor T-cells (CAR-T cells), bispecific antibodies, or antibody-drug conjugates. For now, these treatments are usually reserved to heavily pre-treated patients with a poor outcome. MM drug classes have tremendously extended from historical alkylating agents to current dominant associations with proteasome inhibitors, immunomodulatory agents, and monoclonal anti-CD38/anti SLAMF7 antibodies. Plus, in only a couple of years, several new classes will enter the MM armamentarium, such as cereblon E3 ligase modulators (CELMoDs), selective inhibitors of nuclear export, and peptide-drug conjugates. Among the questions that will need to be answered in the years to come is the position of these new treatments in the therapeutic strategy, as well as the role of minimal residual disease-driven strategies which will be a key issue to elucidate. Through this review, we chose to enumerate and comment on the most recent advances in MM therapeutics which have undergone major transformations over the past decade.

11.
Front Oncol ; 10: 676, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32435618

RESUMO

As the global population is aging and survival in multiple myeloma (MM) is increasing, treating older MM patients, redefined as non-transplant eligible (NTE), is becoming more frequent. Yet, treating these patients remains a real challenge especially because of a marked heterogeneity in the population and an increased susceptibility to treatment toxicity. Indeed, the balance between efficacy and safety must be considered at all time throughout the treatment history for these patients. Therefore, younger and older patients were historically treated in a very different way, even though the safety profile of most anti-myeloma drugs has drastically improved over the years. The emergence of immunotherapy (IT) has largely widened the therapeutic options available in MM and above all has allowed a therapy at optimal dose, and therefore optimal activity, for all patients independently of their frailty features, with no increase in safety issues. Among the novel anti-myeloma IT-based agents, anti-CD38 monoclonal antibodies (mAbs) are now becoming the new backbone of treatment for NTE patients, in association with lenalidomide and dexamethasone. Moreover, several new IT-based drugs are currently being developed and investigated either alone or in association; such as new anti-CD38 mAbs, anti-CD38 mAbs with many different combinations, but also the CAR-T cells, bispecific T-cell engager (BiTEs), or antibody drug conjugate (ADC) targeting BCMA. One would expect that immunotherapy will ultimately change and even transform the MM landscape, even for elderly patients. Immunotherapy represents a shift in treatment paradigm in MM as it provides truly efficient drugs with a very favorable safety profile.

12.
Oncotarget ; 9(35): 23890-23899, 2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-29844860

RESUMO

PURPOSE: Multiple myeloma (MM) remains an incurable disease as tumor cells ultimately resist to all available drugs. Homing of tumor cells to the bone marrow microenvironment, involving especially the CXCR4/SDF-1 axis, allows them to survive, proliferate and resist to therapy. F50067, a humanized anti-CXCR4 IgG1 antibody, has promising preclinical activity in MM.We present a phase I multicenter escalation study in relapsed/refractory MM (RRMM) to determine the maximum tolerated dose (MTD) for F50067 alone and in combination with lenalidomide and low dose dexamethasone (Len-Dex). EXPERIMENTAL DESIGN: 14 end-stage RRMM patients received F50067 single agent (n = 10) or in combination with Len-Dex (n = 4). RESULTS: One dose-limiting toxicity was observed, a grade 4 neutropenia lasting more than 7 days in combination arm. MTD could not be established. Thrombocytopenia was observed in 100% and neutropenia in 92.9% of patients with no cases of febrile neutropenia and no severe bleeding or hematoma. Non-hematological adverse events were of mild to moderate severity.Nine patients (6 in single arm and 3 in combination arm) were evaluable for response, with 66.7% overall response rate (≥PR) in combination arm, and 33.3% of disease control (≥SD) in single agent arm. At the time of study termination, 55.6% had progressed. CONCLUSION: This study suggests that egression of tumor cells to the blood stream can represent a novel therapeutic strategy for MM. However, because of significant hematological toxicity, this study had to be discontinued. Further studies are needed to validate the feasibility of this approach in clinical practice.

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