Mavenclad (cladribine) / EMD Serono - LARVOL DELTA

TREAT-MS: Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial (clinicaltrials.gov) - P=N/A | N=900 | Completed | Sponsor: Johns Hopkins University | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Multiple Sclerosis

Safety and Efficacy of G-CSF with Intensive Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia: A Subgroup Analysis of the Phase II Trial of Venetoclax in Combination with Cladribine, Idarubicin, and Cytarabine (ASH 2024) - P2 | "The trial allowed treating physicians to use filgrastim 300–480 µg daily for prolonged neutropenia or neutropenic fever; a trial amendment integrated pegfilgrastim at a dose of 6 mg SQ once between D5–9 of each cycle...Sixteen (18%) patients had FLT3-ITD — 8 (9%) received gilteritinib and 1 (1%) received midostaurin...FLT3-ITD AML was associated with delayed count recovery, likely due to concurrent TKI use. G-CSF use had no impact on the incidence of AML relapse."

Clinical • Combination therapy • P2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • ASXL1 • BCOR • BCR • FLT3 • KRAS • RUNX1 • SF3B1 • SRSF2 • STAG2 • U2AF1 • ZRSR2

Multicenter study of cladribine in relapsing-remitting multiple sclerosis in patients over 50 years. (PubMed, Farm Hosp) - "Cladribine has demonstrated both clinical and radiological effectiveness in relapsing-remitting multiple sclerosis patients over 50 years of age, with an acceptable safety profile."

Clinical • Journal • CNS Disorders • Genito-urinary Cancer • Infectious Disease • Multiple Sclerosis • Oncology • Prostate Cancer • Septic Shock • Solid Tumor

Predictors of high- versus low-intensity first-line multiple sclerosis treatments. (PubMed, Mult Scler J Exp Transl Clin) - "The first DMT filled was classified as either high- (natalizumab, alemtuzumab, ocrelizumab, rituximab, ofatumumab, cladribine) or low-intensity (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, diroximel fumarate, fingolimod, ponesimod, siponimod, ozanimod)...The minority of MS patients initiated high-intensity treatment although this proportion increased over time, and later years were predictive of high-intensity treatment. Providers had a significant role in the approach selected."

Journal • CNS Disorders • Multiple Sclerosis

HiHat: The HIt HArd and hiT Early in Multiple Sclerosis Trial (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Uppsala University | Not yet recruiting ➔ Recruiting | Initiation date: Apr 2026 ➔ Sep 2026

Enrollment open • Trial initiation date • CNS Disorders • Multiple Sclerosis

Bilateral Herpetic Keratitis following Cladribine Immunosuppression: A Case Report. (PubMed, Case Rep Ophthalmol) - "Visual acuity declined during flares but improved with oral valacyclovir and ganciclovir gel drops. The temporal relationship between lymphocyte depletion and symptom onset suggests impaired cell-mediated immunity as a contributing factor. Clinicians should consider atypical herpetic ocular disease in immunosuppressed patients and may need prolonged antiviral therapy and close monitoring to reduce recurrence and preserve vision."

Journal • Achromatopsia • CNS Disorders • Hematological Disorders • Infectious Disease • Inflammation • Keratitis • Leukopenia • Multiple Sclerosis • Ocular Inflammation • Ophthalmology

Immune reconstitution and tolerance-inducing therapies as promising therapeutic approaches in multiple sclerosis. (PubMed, Neurol Sci) - "Collectively, immune reconstitution and tolerance-inducing therapies represent an emerging shift from lifelong disease control toward durable immune resetting and the possibility of sustained drug-free remission in MS."

Journal • Review • Bone Marrow Transplantation • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • Transplantation

Natalizumab and Tyruko (natalizumab biosimilar) for treating highly active relapsing-remitting multiple sclerosis after at least one disease-modifying therapy: a systematic review and economic model. (PubMed, Health Technol Assess) - "Fingolimod, glatiramer acetate, interferon beta-1a, interferon beta-1b and peginterferon beta-1a were associated with an increased treatment discontinuation (29 studies, 13 interventions)...Data in highly active relapsing-remitting multiple sclerosis were available for fingolimod, ocrelizumab, alemtuzumab, cladribine, interferon beta, autologous haematopoietic stem cell treatment and placebo...60. See the NIHR Funding and Awards website for further award information."

Clinical • Journal • Review • CNS Disorders • Inflammation • Multiple Sclerosis

What is the evidence on immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis? - A Cochrane Review summary with commentary. (PubMed, NeuroRehabilitation) - "High-certainty evidence suggests that natalizumab largely reduces relapses at 12 (RR 0.52, 95% CI 0.43 to 0.63) and 24 months (RR 0.56, 95% CI 0.48 to 0.65), and cladribine (RR 0.53, 95% CI 0.44 to 0.64) and alemtuzumab (RR 0.57, 95% CI 0.47 to 0.68) largely reduce relapses at 24 months. People taking fingolimod, teriflunomide, glatiramer acetate, interferon beta-1a, laquinimod, natalizumab and daclizumab are more likely to discontinue the drug because of unwanted effects. Lack of data for treatment effects beyond two years and poor reporting of adverse events in short-term trials limit the applicability of these findings."

Journal • Review • CNS Disorders • Multiple Sclerosis

Long-term efficacy of cladribine tablets: Results from the MAGNIFY-MS Extension study. (PubMed, Mult Scler) - P4 | "Two years of short-course CladT provided sustained clinical and cognitive benefits, supporting the potential for treatment-free remission in RMS."

Journal • CNS Disorders • Cognitive Disorders • Multiple Sclerosis

French expert opinion on the long-term management of relapsing multiple sclerosis with cladribine tablets beyond year 4. (PubMed, J Neurol) - "A stable profile, which encompasses a large proportion of treated patients, may be managed through continued monitoring or additional treatment, depending on individual presentations and the presence or absence of factors associated with higher likelihood of RMS reactivation before CladT initiation. For patients demonstrating signs of disease activity, options include additional treatment with CladT or transitioning to another HET, according to the severity of inflammatory reactivation."

Journal • Review • CNS Disorders • Multiple Sclerosis

Cladribine Venetoclax in Monocytic AML (clinicaltrials.gov) - P2 | N=10 | Active, not recruiting | Sponsor: University of Colorado, Denver | Recruiting ➔ Active, not recruiting | N=20 ➔ 10 | Trial primary completion date: Oct 2026 ➔ Jun 2026

Enrollment change • Enrollment closed • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Modified Delphi consensus on the use of cladribine tablets in relapsing-remitting multiple sclerosis in North-West Africa. (PubMed, Mult Scler Relat Disord) - "This Delphi consensus provides practical, region-specific guidance to optimize the use of cladribine tablets in RRMS across NWA, aiming to harmonize treatment practices and improve long-term outcomes."

Journal • CNS Disorders • Multiple Sclerosis

Exploring Multiple Sclerosis In Alberta's Diverse Ethnic Populations (CNSF 2026) - "Diverse pwMS were treated with the following DMTs: anti-CD20 therapies (53), dimethyl fumarate (16), glatiramer acetate (9), fingolimod (5), interferon beta-1a (4), natalizumab (1), and cladribine (1). Diverse pwMS are significantly younger at MS onset compared to White pwMS in Alberta. Most diverse pwMS are treated with anti-CD20 therapies."

Clinical • CNS Disorders

Treatment Outcomes of Advanced Combination Therapy in Multiple Sclerosis-Inflammatory Bowel Disease Overlap: Single-centre study. (CNSF 2026) - "MS DMTs were ofatumumab (n=5), cladribine (n=3), siponimod (n=1)...Outcomes included IBD remission with MS clinical/radiologic stability in seven patients, a Crohn's flare on fingolimod resolving after switch to cladribine (n=1), and concurrent MS and Crohn's flares five years post-cladribine requiring dual immunotherapy initiation (n=1). Two patients had simple infections.ConclusionsUp to three quarter of patients achieved MS-IBD stability with newer DMTs, either as monotherapy or dual therapy, underscoring the feasibility of individualized, multidisciplinary care in this rare overlap population."

Clinical • Combination therapy • Metastases • CNS Disorders

Phase Ib/II Trial of Cladribine/Ruxolitinib/Venetoclax in Patients With Relapsed/Refractory T-cell Prolymphocytic Leukemia (clinicaltrials.gov) - P1/2 | N=36 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Leukemia • Oncology • Prolymphocytic Leukemia

The Art of Sequencing Disease-Modifying Therapies in Multiple Sclerosis. (PubMed, Neurol Neuroimmunol Neuroinflamm) - "Following natalizumab, anti-CD20 monoclonal antibodies demonstrate superior control of relapse and MRI activity compared with sphingosine-1-phosphate receptor modulators (S1PRMs)...After S1PRMs, rapid initiation of anti-CD20 therapies or cladribine seems effective, whereas prolonged washout periods increase relapse risk...Future strategies will likely rely on close clinical and biomarker-based monitoring to individualize transitions and identify therapeutic windows. Overall, pragmatic sequencing that anticipates future switches and balances rebound risk against cumulative immunosuppression is essential for optimizing long-term outcomes in MS."

Journal • Review • CNS Disorders • Infectious Disease • Inflammation • Multiple Sclerosis

From Clinical Trial Efficacy to Real-World Effectiveness and Safety: Two-Year Outcomes of Cladribine in Relapsing-Remitting Multiple Sclerosis. (PubMed, J Clin Med) - "The close alignment between our findings and those reported in pivotal clinical trials underscores the external validity of cladribine efficacy beyond controlled study environments. These data provide valuable real-world evidence bridging the gap between controlled research settings and everyday patient care, thereby strengthening the evidence base for cladribine in contemporary MS management."

Journal • Real-world evidence • CNS Disorders • Herpes Zoster • Infectious Disease • Multiple Sclerosis • Varicella Zoster

Switching Natalizumab to Cladribine: a monocentric observational trial in Multiple Sclerosis. (EAN 2026) - "Concomitant administration of corticosteroid therapy was administered orally at the dosage of prednisone 50mg/day, tapered over 30 days or Betametasone 4 mg/day intramuscular for two weeks. Cladribine maintains disease stability and is well tolerated in patients discontinuing Natalizumab. The study provides real-world evidence supporting Cladribine as a successor therapy."

Observational data • CNS Disorders • Infectious Disease • Multiple Sclerosis

T-cell receptor excision circles and Kappa-deleting recombination excision circles as biomarkers of immune aging in multiple sclerosis (EAN 2026) - "DMTs had distinct effects on immune output: TRECs significantly decreased under fingolimod, remained stable with alemtuzumab and cladribine, and increased with other therapies at 1 year. KRECs declined markedly under fingolimod and anti-CD20 therapies, more mildly under dimethyl fumarate and teriflunomide, and increased under natalizumab... TRECs and KRECs primarily reflect immune ageing in MS and are differentially modulated by DMTs. This study prompts future investigations for their role as markers of DMT response."

Biomarker • IO biomarker • CNS Disorders • Multiple Sclerosis

Transfusion-Associated Graft-Versus-Host Disease Risk and Transfusion Requirements After Cladribine in Multiple Sclerosis: Time to Revise Irradiation Policy? (PubMed, Eur J Neurol) - "Current evidence does not clearly support the need for lifelong irradiation after cladribine treatment in pwMS. Time-limited or individualized approaches merit consideration."

Journal • Review • CNS Disorders • Graft versus Host Disease • Immunology • Multiple Sclerosis

Effects of Drugs for the Treatment of Multiple Sclerosis in Severe Acute Respiratory Syndrome Coronavirus 2 Infection on the Expression of Angiotensin-converting Enzyme 2 in vitro. (PubMed, Curr Neuropharmacol) - "Data suggest that drugs used in the treatment of MS can modify ACE2 expression; specifically, fingolimod reduces ACE2 expression and may have a protective role against SARS-CoV-2 infection."

Journal • Preclinical • CNS Disorders • Infectious Disease • Lung Adenocarcinoma • Lung Cancer • Multiple Sclerosis • Non Small Cell Lung Cancer • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor • ACE2 • IL1B • TMPRSS2

Clinical course, safety, and pregnancy outcomes in multiple sclerosis patients treated with cladribine: Single center real-world experience (EAN 2026) - "Cladribine demonstrated high efficacy and a manageable safety profile in this expanded real-world cohort ( n = 145). The incidence of severe lymphopenia was consistent with current literature. While healthy live births were achieved, pregnancy planning and monitoring remain crucial due to potential risks."

Clinical • Real-world • Real-world evidence • Alopecia • CNS Disorders • Herpes Zoster • Multiple Sclerosis • Varicella Zoster

Can Immune Cell Dynamics after Short Course Cladribine Tablets Predict MRI Lesion Activity in MS? Insights from the 4 year MAGNIFY MS Study (EAN 2026) - "CM and Th1 T-cells, along with plasma (CD38+ and short-lived), B-memory, and B-activated cells were associated with MRI-lesion activity. Assessing reconstitution dynamics, especially B- vs T-cell ratios, during the treatment-free period may help predict disease activity and guide long-term disease management. Neuroimaging 2"

Immune cell • IO biomarker • CD4 • CD8

The Effect of Cladribine Tablets on Retinal Microglial Activity in Relapsing Multiple Sclerosis: Optical Coherence Tomography Findings From MAGNIFY-MS (EAN 2026) - P4 | "In our exploratory analysis, CladT treatment reduced overall HRF burden in pwRMS. Baseline GCIPL-HRF was associated with early inflammatory activity, whereas INL-HRF was associated with chronic neurodegenerative changes."

CNS Disorders • Multiple Sclerosis