cladribine
Sources réglementaires consultées
Indications approuvées
- Leucémie à tricholeucocytes active et leucémie lymphoïde chronique B n’ayant pas répondu ou ayant progressé pendant ou après un schéma standard contenant au moins un agent alkylant.
Contre-indications
Absolues
- Hypersensibilité ; grossesse ; allaitement.
Mises en garde cliniques
- Surveiller la numération avant chaque cycle et pendant le nadir. Différer ou modifier le cycle en cas de myélosuppression ; les infections et hémorragies peuvent être graves ou mortelles. — CIMA/AEMPS, ficha técnica 61380
- L’immunosuppression peut provoquer des infections sévères ou un sepsis mortel. Surveiller la numération pendant 4–8 semaines après le traitement. Des doses 4–9 fois supérieures à la dose recommandée ont provoqué une neurotoxicité irréversible. Traiter toute infection active avant le traitement. Si le nombre initial de leucocytes est élevé, administrer allopurinol et hydratation pour prévenir le syndrome de lyse tumorale. — CIMA/AEMPS, ficha técnica 61380
Interactions médicamenteuses
- SévèreAutres analogues nucléosidiques
Mécanisme: Ils peuvent produire une toxicité intracellulaire additive.
Recommandation: L’association n’est pas recommandée.
CIMA/AEMPS, ficha técnica 61380
- SévèreVaccins vivants
Mécanisme: L’immunosuppression peut provoquer une infection vaccinale disséminée.
Recommandation: Les vaccins vivants ne sont pas recommandés pendant l’immunosuppression.
CIMA/AEMPS, ficha técnica 61380
- SévèreAutres myélosuppresseurs ou immunosuppresseurs
Mécanisme: Ils peuvent majorer la myélosuppression, l’immunosuppression et les infections lorsqu’ils sont utilisés avant, pendant ou après la cladribine.
Recommandation: Utiliser avec prudence et coordonner la séquence ainsi que la surveillance hématologique et infectieuse.
CIMA/AEMPS, ficha técnica 61380
- SévèreDidanosine, ténofovir, adéfovir ou autres inhibiteurs de la captation de l’adénosine
Mécanisme: Ils peuvent modifier la captation ou l’activation intracellulaire de la cladribine et altérer l’efficacité ou la toxicité.
Recommandation: L’administration concomitante n’est pas recommandée.
CIMA/AEMPS, ficha técnica 61380
Grossesse et allaitement
Elle est contre-indiquée pendant la grossesse. Utiliser une contraception efficace pendant le traitement et pendant 6 mois après. Ne pas allaiter pendant le traitement ni pendant 6 mois après.
Bibliographie récente (PubMed)
Langerhans cell histiocytosis (LCH) can affect children and adults with a wide variety of clinical manifestations, including unifocal, single-system multifocal, single-system pulmonary (smoking-associated), or multisystem disease. The existing paradigms in the management of LCH in adults are mostly derived from the pediatric literature. Over the last decade, the discovery of clonality and MAPK-ERK pathway mutations in most cases led to the recognition of LCH as a hematopoietic neoplasm, opening the doors for treatment with targeted therapies. These advances have necessitated an update of the existing recommendations for the diagnosis and treatment of LCH in adults. This document presents consensus recommendations that resulted from the discussions at the annual Histiocyte Society meeting in 2019, encompassing clinical features, classification, diagnostic criteria, treatment algorithm, and response assessment for adults with LCH. The recommendations favor the use of 18F-Fluorodeoxyglucose positron emission tomography-based imaging for staging and response assessment in the majority of cases. Most adults with unifocal disease may be cured by local therapies, while the first-line treatment for single-system pulmonary LCH remains smoking cessation. Among patients not amenable or unresponsive to these treatments and/or have multifocal and multisystem disease, systemic treatments are recommended. Preferred systemic treatments in adults with LCH include cladribine or cytarabine, with the emerging role of targeted (BRAF and MEK inhibitor) therapies. Despite documented responses to treatments, many patients struggle with a high symptom burden from pain, fatigue, and mood disorders that should be acknowledged and managed appropriately.
The combination of venetoclax and 5-azacitidine (5-AZA) for older or unfit patients with acute myeloid leukemia (AML) improves remission rates and survival compared with 5-AZA alone. We hypothesized that the addition of venetoclax to cladribine (CLAD)/low-dose araC (low-dose cytarabine [LDAC]) alternating with 5-AZA backbone may further improve outcomes for older patients with newly diagnosed AML. This is a phase II study investigating the combination of venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA in older (≥ 60 years) or unfit patients with newly diagnosed AML. The primary objective was composite complete response (CR) rate (CR plus CR with incomplete blood count recovery); secondary end points were overall survival, disease-free survival (DFS), overall response rate, and toxicity. A total of 60 patients were treated; median age was 68 years (range, 57-84 years). By European LeukemiaNet, 23%, 33%, and 43% were favorable, intermediate, and adverse risk, respectively. Fifty-six of 60 evaluable patients responded (composite CR: 93%) and 84% were negative for measurable residual disease. There was one death (2%) within 4 weeks. With a median follow-up of 22.1 months, the median overall survival and DFS have not yet been reached. The most frequent grade 3/4 nonhematologic adverse events were febrile neutropenia (n = 33) and pneumonia (n = 14). One patient developed grade 4 tumor lysis syndrome. Venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA is an effective regimen among older or unfit patients with newly diagnosed AML. The rates of overall survival and DFS are encouraging. Further study of this non-anthracycline-containing backbone in younger patients, unfit for intensive chemotherapy, as well as comparisons to standard frontline therapies is warranted. The amount of cladribine in milk is low with oral doses of 10 to 20 mg daily used in multiple sclerosis. Data in one patient indicates that the drug is rapidly eliminated over 24 hours
Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biological agents. Although each one of these therapies reduces relapse frequency and slows disability accumulation compared to no treatment, their relative benefit remains unclear. This is an update of a Cochrane review published in 2015. To compare the efficacy and safety, through network meta-analysis, of interferon beta-1b, interferon beta-1a, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta-1a, daclizumab, laquinimod, azathioprine, immunoglobulins, cladribine, cyclophosphamide, diroximel fumarate, fludarabine, interferon beta 1-a and beta 1-b, leflunomide, methotrexate, minocycline, mycophenolate mofetil, ofatumumab, ozanimod, ponesimod, rituximab, siponimod and steroids for the treatment of people with RRMS. CENTRAL, MEDLINE, Embase, and two trials registers were searched on 21 September 2021 together with reference checking, citation searching and contact with study authors to identify additional studies. A top-up search was conducted on 8 August 2022. Randomised controlled trials (RCTs) that studied one or more of the available immunomodulators and immunosuppressants as monotherapy in comparison to placebo or to another active agent, in adults with RRMS. Two authors independently selected studies and extracted data. We considered both direct and indirect evidence and performed data synthesis by pairwise and network meta-analysis. Certainty of the evidence was assessed by the GRADE approach. We included 50 studies involving 36,541 participants (68.6% female and 31.4% male). Median treatment duration was 24 months, and 25 (50%) studies were placebo-controlled. Considering the risk of bias, the most frequent concern was related to the role of the sponsor in the authorship of the study report or in data ma
- High-Efficacy Therapies for Treatment-Naïve Individuals with Relapsing-Remitting Multiple Sclerosis.
There are > 18 distinct disease-modifying therapy (DMT) options covering 10 mechanisms of action currently approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS). Given the multitude of available treatment options, and recent international consensus guidelines offering differing recommendations, there is broad heterogeneity in how the DMTs are used in clinical practice. Choosing a DMT for newly diagnosed patients with MS is currently a topic of significant debate in MS care. Historically, an escalation approach to DMT was used for newly diagnosed patients with RRMS. However, the evidence for clinical benefits of early treatment with high-efficacy therapies (HETs) in this population is emerging. In this review, we provide an overview of the DMT options and MS treatment strategies, and discuss the clinical benefits of HETs (including ofatumumab, ocrelizumab, natalizumab, alemtuzumab, and cladribine) in the early stages of MS, along with safety concerns associated with these DMTs. By minimizing the accumulation of neurological damage early in the disease course, early treatment with HETs may enhance long-term clinical outcomes over the lifetime of the patient. Disease-modifying therapies (DMTs) can help people with multiple sclerosis (MS) by changing the way that their MS develops over time. Some people with MS have relapses when their symptoms get worse, followed by recovery when their MS is remitting. This is called relapsing–remitting MS (RRMS). DMTs can reduce both the number and the severity of relapses. They can also delay the nerve damage that relapses cause. A range of DMTs are approved for treating people with RRMS. These treatments work in different ways, and international treatment guidelines vary on their recommendations for using DMTs in the clinic. Selecting DMTs for people with newly diagnosed RRMS is still a topic of discussion. Previously, people with RRMS only received the more effective high