Mavenclad (cladribine) / EMD Serono - LARVOL DELTA

Phase 2 trial of encorafenib plus binimetinib for patients with BRAF V600 mutated relapsed/refractory hairy cell leukemia (ASH 2025) - "Background : Hairy cell leukemia (HCL) is an indolent B-cell leukemia characterized by durable completeremissions to purine analogs cladribine or pentostatin, but repeated relapses and cumulative toxicity torepeated purine analog courses...Vemurafenib was combined with rituximab,achieving 57% MRD-free CRs... Encorafenib-binimetinib is highly effective in relapsed/refractory HCL and was well toleratedwhen dose reductions occurred as needed. Compared to dabrafenib-trametinib, the lower incidence offever (11% vs 58%, p<0.0001) is a major advantage. The CR rate of 93% without rituximab isunprecedented for BRAF inhibition in HCL."

Clinical • P2 data • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Melanoma • Musculoskeletal Pain • Pancreatitis • Retinal Disorders • Solid Tumor • BRAF

Efficacy and safety of melphalan/TBI-based conditioning regimens (MCAC/TCAC) for autologous HSCT in adult acute lymphoblastic leukemia: A multicenter, prospective cohort study (ASH 2025) - "The MCAC regimen consisted of melphalan 70mg/m² on days -8 and -7, followed by cyclophosphamide (CY) 40 mg/kg on days -6 and -5, and acombination of cladribine 5 mg/m² with cytarabine (Ara-C) 2 g/m² on days -4, -3, and -2. In contrast, the rates offungal infections (3/55, 5.5% vs. 3/26, 11.5%) and viral infections (5/55, 9.1% vs. 3/26, 11.5%) werecomparable between the two groups.ConclusionThese preliminary findings suggest that the MCAC regimen appears to be a viable and safe alternative toTBI-based conditioning for auto-HSCT in adult ALL patients who achieve and sustain early MRD negativity(by both flow cytometry and molecular biology). However, as the follow-up duration for both groupsremains short, long-term efficacy and safety require further investigation."

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Central Nervous System Leukemia • Cerebral Hemorrhage • Gastroenterology • Hematological Malignancies • Hepatology • Infectious Disease • Infertility • Leukemia • Liver Failure • Metabolic Disorders • Mucositis • Sexual Disorders • Stomatitis • T Acute Lymphoblastic Leukemia

Long-term outcomes of patients with hairy cell leukemia treated with first-line cladribine in British Columbia (ASH 2025) - "Of these 65 pts, 45 (69%) were re-treated with PAalone (cladribine 40; fludarabine 5), 14 (22%) with a PA (14 of which received fludarabine) plus R, 2 withsingle-agent R, 1 with RCHOP, and 3 were observed. When comparing those re-treated with PA aloneversus PA plus R, median PFS2 was 8.6 y vs. not reached (P=0.03), and median OS2 was 23.7 y vs. notreached (P=0.62), respectively.During the follow-up period, 17/62 pts received 3L therapy including: re-treatment with cladribinemonotherapy in 3 pts, fludarabine plus R in 8, bendamustine plus R in 1, single-agent R in 4, and 1 patienteach received ibrutinib and vemurafenib with R. 5/17 pts went on to receive 4L therapy and 2/5 ptsreceived 5L therapy, primarily with alternate PAs and other novel agents such as anti-CD22 mAbs,Bruton's tyrosine kinase or BRAF inhibitors.A total of 74 pts (36% of the entire cohort) died...Our study suggests that combining a PA with an anti-CD20 mAb (mostcommonly fludarabine and R in this..."

Clinical • Gastrointestinal Disorder • Hairy Cell Leukemia • Hematological Malignancies • Indolent Lymphoma • Infectious Disease • Leukemia • Melanoma • Septic Shock • Solid Tumor

BH25 Alopecia in a patient undergoing multiple treatments for multiple sclerosis: a rare presentation and case review. (PubMed, Br J Dermatol) - "She was initiated on glatiramer acetate (GA) in 2019...Following this, monthly infusions of natalizumab (eight doses) were administered in 2024...Most recently, she was prescribed cladribine, which caused scalp irritation, including burning and itching a week after each course...Br J Dermatol 2023; 188 (Suppl. 4): ljad113.167]."

Journal • Review • Alopecia • Anorexia • Bulimia • CNS Disorders • Endocrine Disorders • Hematological Disorders • Immunology • Multiple Sclerosis

Expert consensus on the clinical use of cladribine tablets for treating relapsing multiple sclerosis in the asia-pacific region. (PubMed, Mult Scler Relat Disord) - "The consensus encompasses patient selection criteria, therapeutic strategies, monitoring protocols, and safety considerations, tailored to the unique demographic and healthcare landscapes of APAC countries."

Journal • CNS Disorders • Multiple Sclerosis

Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress Damage. (PubMed, Int J Mol Sci) - "However, cladribine protected differentiated SH-SY5Y human neuroblastoma cell line from oxidative stress-related cell death. In conclusion, using different in vitro cell models, we demonstrate that cladribine maintains the normal function of CNS glia and protects neuronal cells from oxidative stress damage."

Journal • CNS Disorders • Immunology • Multiple Sclerosis • Neuroblastoma • Oncology • Solid Tumor

Addressing autoimmune comorbidities in multiple sclerosis: A case report of ulcerative colitis remission in a patient treated with cladribine tablets. (PubMed, Mult Scler) - "This case highlights cladribine's potential in managing both MS and UC, though its efficacy faded over time. Further research into shared immunopathogenesis and therapeutic strategies in co-existing autoimmune diseases is warranted."

Journal • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Multiple Sclerosis • Ulcerative Colitis

Selected aspects of epidemiology of multiple sclerosis in Poland: a multicenter pilot study. (PubMed, Neurol Neurochir Pol) - "This study highlights substantial progress in the diagnostic and therapeutic management of MS in Poland over the past 15 years. The widespread implementation of MRI and CSF analysis, alongside significantly improved access to DMTs, has contributed to notably better clinical outcomes. These improvements are reflected in reduced relapse rates, slower disability progression, and a decreased prevalence of secondary progressive MS."

Journal • CNS Disorders • Multiple Sclerosis

Plasma neurofilament light chain to evaluate response during cladribine treatment in multiple sclerosis. (PubMed, J Neurol Sci) - "Cladribine significantly reduced pNfL levels, which stabilized at values comparable to matched healthy controls, confirming its strong efficacy with minimal disease activity during follow-up."

Biomarker • Clinical • Journal • Retrospective data • Review • CNS Disorders • Multiple Sclerosis • NEFL • Plasma NfL

Switching from anti-CD20 therapies to cladribine and vice versa - Analysis of a German relapsing multiple sclerosis cohort. (PubMed, Neurotherapeutics) - "Notably, the prevalence of hypogammaglobulinemia decreased after switching from anti-CD20 therapies to cladribine. These results indicate that patients with active RMS can achieve clinical stabilization after switching therapies in either direction, underscoring the complementary mechanisms of action and the safety of such an approach in real-world practice."

Journal • CNS Disorders • Multiple Sclerosis • GFAP • NEFL

Cladribine: A useful treatment option in multiple sclerosis patients with autoimmune comorbidities. (PubMed, Mult Scler) - No abstract available

Journal • CNS Disorders • Immunology • Multiple Sclerosis

Cladribine monotherapy in a patient with coexisting Crohn's disease and multiple sclerosis. (PubMed, Mult Scler) - "Cladribine is an immune reconstitution therapy targeting T and B lymphocytes, with additional immunomodulatory effects that may benefit both conditions. This case highlights the potential of cladribine as a reliable treatment option in selected patients with concomitant CD and MS, warranting further investigation."

Journal • Monotherapy • CNS Disorders • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • Multiple Sclerosis

Xanthoma Disseminatum in the Largest Single-Center Real-World Cohort: Over Five Years of Follow-up (ISDS 2025) - "Regimens included cladribine and real-world non-cladribine strategies (some incorporating sirolimus, abrocitinib, or trametinib). This largest single-center XD cohort with long follow-up supports a pragmatic care pathway: cladribine induction with rapid onset and no observed progression, multidisciplinary baseline evaluation given frequent mucosal/airway and pituitary involvement, and cladribine re-induction at relapse. Non-cladribine strategies also achieved high overall responses, although drug-specific estimates are limited by small numbers. The cycle-indexed, infection-aware monitoring framework is readily adoptable, and the immune signals warrant prospective validation."

Clinical • Real-world • Real-world evidence • Endocrine Disorders • Infectious Disease • Metabolic Disorders • IL6 • TNFA

Is therapy-free remission a realistic goal with cladribine tablets in multiple sclerosis? New insights into the mechanism of action and clinical implications of immune reconstitution with cladribine tablets in MS therapy. (PubMed, J Neurol) - "This narrative review discusses existing and emerging efficacy and safety data for cladribine tablets in MS and links these learnings to different patient profiles encountered in clinical practice. These include young patients with newly diagnosed RMS, young patients with highly active disease, and older patients switching from anti-CD20 antibodies or spingosine-1-phosphate modulators."

Journal • Review • CNS Disorders • Multiple Sclerosis

Cyclodextrin Complexes for Clinical Translatability: Applications for Cladribine and Retrometabolically Designed Estredox. (PubMed, Int J Mol Sci) - "Cladribine-HPβCD tablets (Mavenclad) offer a convenient, effective, and well-tolerated oral therapy for multiple sclerosis, achieving worldwide approval and significant clinical success. Overall, the developments summarized here underscore the importance of tailored cyclodextrin-based approaches for overcoming barriers in drug formulation for compounds with challenging physicochemical properties, and demonstrate the versatility and clinical impact of CD inclusion complexes in modern pharmaceutical development."

Journal • Review • CNS Disorders • Multiple Sclerosis

Safety of disease-modifying therapies in multiple sclerosis: real-world data from the Austrian MS Treatment Registry (AMSTR). (PubMed, J Neurol) - "The safety data from the AMSTR do not reveal any new safety issues, particularly regarding neoplasms and infections. Hence, people with MS as well as their treating neurologists are reassured to continue treatment with DMT, as the benefit-risk profile of DMT could be reaffirmed."

Journal • Real-world evidence • Basal Cell Carcinoma • CNS Disorders • Endocrine Disorders • Infectious Disease • Multiple Sclerosis • Non-melanoma Skin Cancer • Oncology

Minimal association between Th1-specific responses to COVID-19 vaccines and SARS-CoV-2 breakthrough infections in multiple sclerosis patients receiving disease-modifying therapies. (PubMed, Front Immunol) - "Fingolimod-treated patients showed the weakest response with significantly reduced IFN-γ and IL-2 levels compared to HCWs (both p<0.0001), as well as to ocrelizumab (p=0.0018 and p=0.0002, respectively) and cladribine/IFN-β-treated patients (p=0.041 and p<0.0001, respectively). Spike-specific T-cell response did not associate with a higher protection against BI. This study provides an in-depth immunological characterization of the spike-specific T-cell response in PwMS under DMTs, evaluating immunological biomarkers whose relevance may extend beyond COVID-19 for studying immune responses to other infections and vaccinations."

Journal • CNS Disorders • Infectious Disease • Multiple Sclerosis • Novel Coronavirus Disease • Respiratory Diseases • IFNB1 • IFNG • IL2 • TNFA

Post-marketing safety profile of cladribine in multiple sclerosis: a disproportionality analysis based on the FDA adverse event reporting system. (PubMed, Int J Clin Pharm) - "This study not only corroborates previously established risks associated with cladribine but also uncovers new potential safety signals, highlighting the importance of vigilance for early acute toxicity."

Adverse events • Journal • P4 data • Alopecia • Cardiovascular • CNS Disorders • Endocrine Disorders • Hematological Disorders • Hepatology • Immunology • Infectious Disease • Inflammatory Arthritis • Leukopenia • Liver Failure • Migraine • Multiple Sclerosis • Myocardial Infarction • Nephrology • Ocular Inflammation • Ophthalmology • Pain • Pneumonia • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Septic Shock • Uveitis

Clinical Outcomes of Patients with AML Receiving Lower Intensity Chemotherapy with or without the Use of Granulocyte-Colony Stimulating Factor (GCSF) (ASH 2024) - "Introduction : Lower intensity chemotherapy combined with the BCL2 inhibitor venetoclax (VEN) is the standard for newly diagnosed AML among patients (pts) aged ≥ 75 years (yrs) or those ineligible for intensive therapy...We evaluated count recovery, incidence of infection/febrile neutropenia (FN), overall survival (OS), and relapse-free survival (RFS) in pts with newly diagnosed AML treated with lower intensity therapy with or without GCSF.Methods : This retrospective study included pts with newly diagnosed AML treated with VEN in combination with a hypomethylating agent (HMA) (intravenous [IV] azacitidine, IV decitabine, or oral decitabine/cedazuridine [ASTX]) or with cladribine + low-dose cytarabine (CLAD/LDAC)...The use of GCSF appeared to enhance count recovery in pts, allowing more patients to reach an ANC>1 at the end of C1. The use of GCSF should be explored as a viable option to enhance count recovery and potentially mitigate infection in responding pts after..."

Clinical data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Infectious Disease • Neutropenia • Septic Shock

Efficacy and Safety of Gilteritinib-Based Therapy Combinated with Allo-HSCT in Relapsed or Refractory Acute Myeloid Leukemia Patients with Positive FLT3-ITD Mutation (ASH 2024) - "Combination scheme including gilteritinib + venetoclax (Ven) ± azacitidine (AZA)/decitabine (DAC) (n=18), gilteritinib + Ven + DAC + Cladribine (n=1), gilteritinib + IA (idarubicin, cytarabine) (n=1) and gilteritinib + AZA + lower-dose HAAG regime (homoharringtonine, cytarabine, aclarubicin, G-CSF) (n=3). Additionally, gilteritinib maintenance therapy after allo-HSCT has demonstrated a significant enhancement in patients' survival. It is crucial to closely monitor and manage any adverse events that may occur during treatment."

Clinical • Acute Myelogenous Leukemia • Agranulocytosis • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Granulocytopenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Neutropenia • Oncology • Thrombocytopenia • FLT3

Acute Leukemias of Ambiguous Lineage Have Durable Response to Hypomethylating Agents Plus Venetoclax in Older Patients (ASH 2023) - "Frontline HMA/Ven was defined as Ven plus azacytydine, decitabine, or oral decitabine/cedazuridine (one patient had initial HMA monotherapy followed by HMA/Ven). Intensive chemotherapy included patients who received variations of standard ALL or AML IC regimens (hyper- or mini-hyper-CV[A]D, cytarabine plus daunorubicin or idarubicin, or cladribine plus idarubicin and cytarabine) with or without Ven. Tyrosine kinase inhibitors including midostaurin or gilteritinib were added for patients with fms-like tyrosine kinase 3 (FLT3) mutations... Of 16 patients, 7 received frontline HMA/Ven. B/myeloid was the most common disease type (n=8), followed by T/myeloid (n=4), AUL (n=3), and 1 patient with B/T/myeloid disease. The median age was 74 years (interquartile range [IQR] 62-80)."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • ASXL1 • FLT3 • RUNX1 • SRSF2 • TP53

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

Cladribine and Low-Dose Cytarabine-Based Salvage Therapy for Relapsed/Refractory AML in a Predominantly Venetoclax-Exposed Cohort (ASH 2023) - "Clad/LDAC and clad/LDAC/ven represent feasible salvage induction strategies for R/R AML that may be administered outpatient and associated with minimal toxicity. Favorable response rates occurred in a subgroup of patients who failed frontline HMA/ven, in which there is an unmet need."

Acute Kidney Injury • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Nephrology • Neutropenia • Oncology • Renal Disease • ASXL1 • CSF3R • NF1 • SETBP1 • U2AF1

Phase I Trial Combining Venetoclax with Cladribine, Cytarabine, G-CSF, and Mitoxantrone (CLAG-M) for Patients with Acute Myeloid Leukemia (AML) and High-Grade Myeloid Neoplasms (ASH 2024) - P1/2 | "Previous studies have successfully combined venetoclax with fludarabine, cytarabine, idarubicin, and G-CSF (DiNardo et. Discussion : The recommended phase 2 dose is DL 3 : G-CSF 5 mcg/kg days 0-5, cladribine 5 mg/m2 days 1-5, cytarabine 1.5 g/m2 days 1-5, mitoxantrone 16 or 18 mg/m2 days 1-3, and venetoclax 400 mg days 1-14. The results of this phase 1 trial support the design and implementation of a planned phase 2 trial to examine the efficacy of combining CLAG-M and venetoclax."

Clinical • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Infectious Disease • Respiratory Diseases • Septic Shock

Venetoclax Combined with Cladribine, Idarubicin, Cytarabine (CLIA) Results in Higher Remission Rates over Conventional 7+3 Chemotherapy without Increased Toxicity in Newly Diagnosed Acute Myeloid Leukemia (ASH 2024) - "Conclusion : This single center analysis shows that induction therapy using CLIA+V resulted in significantly higher CCR, MRD-negativity, and proportion of patients proceeding to alloHSCT compared to 7+3 among newly diagnosed AML patients without increased toxicity. Survival outcomes were also improved among CLIA+V treated patients however, longer follow-up time is needed."

Clinical • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • FLT3 • IDH1 • IDH2