cladribine / Generic mfg. - LARVOL DELTA

Cladribine and low-dose cytarabine as first salvage after hypomethylating agent and venetoclax in acute myeloid leukemia. (PubMed, Leuk Res) - "Serial molecular profiling identified heterogeneous patterns of clonal evolution across the treatment trajectory, including exploratory observations of high Clad/LDAC ORR in patients with emergent RAS-pathway clones at HMA/Ven failure. These findings highlight Clad/LDAC-based therapy as a salvage option with modest clinical activity following HMA/Ven."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • TP53

Fibromyalgia Turned Refractory Celiac Disease-Associated Myalgia: Resolution Following Cladribine Therapy (ACG 2026) - "Dietitian-verified GFD adherence and failed open-capsule budesonide prompted cladribine over two cycles, infliximab having been initially planned for presumed type 1. (A) Lower-power view showing well-preserved villous architecture (hematoxylin-eosin stain, original magnification x 100). (B) Higher-power view showing intraepithelial lymphocytosis (hematoxylin-eosin stain, original magnification x 400)."

IO biomarker • Celiac Disease • Fibromyalgia • Hematological Malignancies • Immunology • Lymphoma • Musculoskeletal Diseases • Musculoskeletal Pain • Rheumatology • T Cell Non-Hodgkin Lymphoma • CD8

Adult-Onset Central Nervous System Erdheim-Chester Disease Successfully Treated With Cladribine and Cytarabine: Case Report and Literature Review. (PubMed, EJHaem) - "This case suggests that combination chemotherapy may represent an optimal therapeutic strategy for adult patients with CNS ECD. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission."

Journal • CNS Disorders • Rare Diseases

Phase II study of cladribine, idarubicin, and ara-C (CLIA) with or without sorafenib as initial therapy for patients with acute myeloid leukemia. (PubMed, Am J Hematol) - "CLIA was safe and effective in young, fit patients with newly diagnosed AML with inferior outcomes among patients with ts-AML. The addition of sorafenib to CLIA in FLT3-ITD mutated AML resulted in high rates of durable remission and excellent long-term survival."

Journal • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • FLT3

Addition of Sorafenib to Cladribine, High-Dose Cytarabine, G-CSF, and Mitoxantrone (CLAG-M) in Adults with Newly-Diagnosed Acute Myeloid Leukemia (AML) and High-Grade Myeloid Neoplasms Independent of FLT3-Mutation Status: Final Results of a Phase 1/2 Study (ASH 2022) - P1/2 | "Addition of sorafenib to CLAG-M produces high rates of MRDneg CR in newly diagnosed AML patients ≤60 and prolongs OS and EFS in multivariate analysis compared to historical, matched control cohort receiving GLAG-M alone, a benefit that was particularly evident in patients with intermediate-risk disease."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Transplantation • CSF3 • FLT3

Precision-guided therapy in dialysis-dependent classic hairy cell leukemia: a case report. (PubMed, Front Oncol) - "We present a novel case of a 43-year-old man on chronic hemodialysis secondary to suspected autosomal dominant polycystic kidney disease diagnosed with classic BRAF V600E-mutated HCL, treated with low-dose vemurafenib in combination with anti-CD20 therapy...This report highlights the feasibility and efficacy of BRAF-targeted therapy combined with an anti-CD20 antibody in a young dialysis-dependent HCL patient, expanding therapeutic options for this high-risk population. Further prospective studies and case series are needed to guide management in this unique clinical context."

Journal • Autosomal Dominant Polycystic Kidney Disease • Chronic Kidney Disease • Fibrosis • Genetic Disorders • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Nephrology • Oncology • Polycystic Kidney Disease • Renal Disease

Clinical Outcomes of Adults With Core Binding Factor Acute Myeloid Leukemia (CBF‑AML): A Single Center Experience (SOHO 2023) - "Other regimens included: cladribine, idarubicin and cytarabine (CLIA, n=1), fludarabine, cytarabine and gemtuzumab ozogamicin (FLAG-GO, n=1), idarubicin and cytarabine (3+7 regimen, n=1) and decitabine, venetoclax and GO (n=1). Although CBF-AML is considered a favorable risk AML, outcomes for relapsed disease remains poor. Incorporation of GO and CD117 tyrosine kinase inhibitors (i.e. dasatinib) into induction and consolidation regimens may mitigate the relapse risk and improves long-term outcomes."

Clinical • Clinical data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • KIT

Phase II Study of Cladribine with Low Dose Cytarabine and Venetoclax Alternating with Azacytidine and Venetoclax for Newly Diagnosed Acute Myeloid Leukemia (ASH 2024) - P2 | "Conclusions : CLAD-LDAC-VEN alternating with AZA + VEN produces an excellent rate of CR/CRi with high rates of MRD negativity , translating into favorable long term OS and EFS in patients aged ≥ 60 yrs or those unfit for intensive chemotherapy. Benefit was seen across most genomically defined subgroups, including those with RAS mutations, where an HMA-Ven alone approach is associated with a mOS of 12 months."

P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • DDX41 • DNMT3A • FLT3 • KRAS • NPM1 • TET2 • TP53

Clinical Outcomes Associated with NPM1 Mutations in Newly Diagnosed AML (ASH 2024) - "High intensity chemotherapy (HIC) was given for 190 NPM1mt pts (48%), of which 46 pts (12%) had the addition of venetoclax (HIC+Ven), whereas 66 pts (17%) received a hypomethylating agent + Ven (HMA+Ven), 32 pts (8%) received cladribine with low-dose cytarabine + Ven (Clad LDAC Ven) and 106 pts (27%) received other lower-intensity treatments. Notably, therapy-related status or adverse risk features by ELN did not predict outcomes. Conclusion : In conclusion, older age, worse performance status, FLT3-ITD co-mutation, and EMD predicted for worse outcomes in NPM1mt AML treated with HIC whereas older age was the only predictor of outcomes in those receiving HMA + venetoclax."

Clinical • Clinical data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelofibrosis • Oncology • DNMT3A • FLT3 • KRAS • NPM1 • NRAS • SRSF2 • TET2

Lintuzumab-Ac225 with Combination with Intensive Chemotherapy Yields High Response Rate and MRD Negativity in R/R AML with Adverse Features (ASH 2022) - "Induction consisted of G-CSF, 300mcg/d, given D1-6, cladribine 5mg/m2, given D2-6, cytarabine 2g/m2, given D2-6, and mitoxantrone 10mg/m2, given D2-4. Actimab-A at 0.75uCi/kg, combined with CLAG-M is feasible and safe, and this combination demonstrates a high response rate and MRD negativity in a high-risk AML population. Pharmacokinetics at the RP2D indicate rapid drug clearance. Furthermore, responses appear durable, particularly among patients who are able to proceed to alloHCT."

Minimal residual disease • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Infectious Disease • Mucositis • Neutropenia • CD33 • CSF3 • MCL1 • TP53

Cladribine, idarubicin, and cytarabine (CLIA) for patients with relapsed and/or refractory acute myeloid leukemia: A single-center, single-arm, phase 2 trial. (PubMed, Cancer) - P2 | "CLIA is effective for patients with R/R AML and offers a safety profile similar to that of other intensive regimens (ClinicalTrials.gov identifier NCT02115295)."

Journal • P2 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Transplantation • FLT3

A Rare Case of ZBTB16::RARA Fusion Acute Myeloid Leukemia Mimicking Acute Promyelocytic Leukemia: Diagnostic Challenges and Successful CLIA + Venetoclax Therapy (SOHO 2026) - "The zinc finger and BTB domain-containing 16 (ZBTB16):: retinoic acid receptor alpha (RARA) fusion, also known as promyelocytic leukemia zinc finger (PLZF)::RARA, is a rare variant RARA fusion rearrangement (<1% of cases) that phenotypically mimics acute promyelocytic leukemia (APL) but is resistant to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) due to the PLZF repressive domain...The patient received induction cladribine, idarubicin, cytarabine (CLIA) plus venetoclax...Supportive care included hydroxyurea, transfusions, and prophylaxis...Venetoclax-based regimens represent a promising approach in this rare entity. Long-term follow-up and potential consolidation with transplant are planned."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Wilms Tumor • CD2 • CD34 • CD38 • KIT • NCAM1 • RARA • SMARCB1 • SMARCD3 • WT1 • ZBTB16

Frontline Systemic Therapeutic Patterns and Outcomes in Rosai-Dorfman Disease: A Multicenter Retrospective Analysis (SOHO 2026) - " Of 44 patients, 27 received targeted therapy (cobimetinib, n = 26; trametinib, n = 1) and 17 received fixedduration chemotherapy (methotrexate, n = 7; cladribine/cytarabine, n = 5; vinblastine/vindesine, n = 3; cyclophosphamide, n = 2). Both chemotherapy and targeted therapy demonstrated clinically meaningful ORR and PFS. Although small sample size prevented statistical comparison, a greater proportion of targeted therapy patients required next-line therapy, reflecting higher discontinuation rates from AEs. While preliminary data suggest both treatment approaches may be effective, larger studies would provide more definitive insights."

Retrospective data • Oncology • BRAF • DNMT3A • KRAS • MAP2K1 • MAP2K2 • NRAS

Myeloablative Fractionated Busulfan Conditioning Regimen with Venetoclax in Patients with AML/MDS: Prospective Phase II Clinical Trial (TCT-ASTCT-CIBMTR 2022) - P2 | "Then, inpatient fludarabine 10 mg/m 2 , and cladribine 10 mg/m 2 were given followed by Bu on days -6 to -3. Venetoclax can be safely added to the fractionated busulfan regimen. Early data on efficacy appear promising."

Clinical • P2 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Febrile Neutropenia • Graft versus Host Disease • Hematological Disorders • Immunology • Mucositis

Myelodysplasia-related mutation dynamics and outcomes in newly diagnosed (ND) acute myeloid leukemia (AML) treated with low-intensity therapy (LIT). (ASCO 2026) - "Background: Outcomes of patients (pts) with ND AML with myelodysplasia related gene mutations (MRMs), while traditionally adverse, appear to be better with LIT regimens + venetoclax (Ven)...171 pts (92%) were treated with LIT+Ven and 14 (8%) LIT without Ven; 105 (57%) received hypomethylating agents based, and the rest (43%) received cladribine + low-dose cytarabine based LIT... In our analysis, the status of MRM clearance at CR/CRi in LIT treated AML with baseline MRM affected survival outcomes, including in pts FCM MRD- at CR/CRi."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • ASXL1 • BCOR • FLT3 • IDH2 • NPM1 • RAS • RUNX1 • SF3B1 • SRSF2 • STAG2 • TP53 • U2AF1 • ZRSR2

Outcomes in patients with newly diagnosed Acute Myeloid Leukemia with KMT2A rearrangement treated with cladribine, idarubicin, cytarabine (CLIA) with or without venetoclax (ASH 2025) - P2 | "The 2-year EFS was 81% and 50% for CLIA-Ven and CLIA, respectively (HR 0.28, p=0.09).The 2-year OS was 81% and 50% for CLIA-Ven and CLIA, respectively (HR 0.37, p=0.19).There were a total of 3 deaths in the CLIA arm: 1 death was treatment related mortality on day 10 of firstcycle of the CLIA due to DAH and intracranial bleed and two deaths were secondary to relapsed disease.There were 3 deaths in CLIA-Ven arm: 1 death was due to severe COVID-19 related complication after 2cycles of chemo, 1 death due to infectious complications 21 days post Allo SCT and 1 death was due torelapsed disease. ConclusionAmong young and fit patients with newly diagnosed AML with KMT2Ar, IC with CLIA induced high rates ofMRD negative remissions, allowing a majority of patients to proceed with a potentially curative alloSCT.The addition of venetoclax with CLIA appeared to produce a higher rate of MRD negative completeremission, low rate of relapse, and promising long term survival in a high..."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • CDKN1A • KMT2A • KRAS • NRAS • TET2

OUTCOMES OF ADULT PATIENTS WITH NEWLY DIAGNOSED IDH-MUTATED ACUTE MYELOID LEUKEMIA RECEIVING INTENSIVE CHEMOTHERAPY PLUS VENETOCLAX (EHA 2025) - P1/2, P2 | "This was a retrospective pooled analysis of two clinical trials of cladribine, idarubicin, and cytarabine + VEN (CLIA+VEN, NCT02115295) and fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin + VEN (FLAG-IDA+VEN, NCT03214562). Venetoclax combined with IC results in a high rate of MRD-negative remissions and impressive OS in newly diagnosed, IDH-mutated AML. IDH1-mutated AML had lower response rates and OS, possibly due to a higher proportion of concurrent adverse cytomolecular features. Randomized trials are needed to determine the optimal induction regimen for patients with IDH mutations."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1

Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial. (PubMed, Lancet Haematol) - P2 | "Venetoclax added to CLIA was safe and active in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome, producing high rates of durable MRD-negative remissions and encouraging event-free survival and overall survival."

Clinical • IO biomarker • Journal • P2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • FLT3

Outcomes of Patients (pts) with Newly Diagnosed Acute Myeloid Leukemia (AML) and TP53 mutation/Loss Treated on the Phase 2 Study of Venetoclax (Ven) Added to Alternating Cladribine (Clad) Plus Low-Dose Cytarabine (LDAC) and Azacitidine (Aza): A Subgroup Analysis (ASH 2023) - P2 | "The phase 2 trial of Ven added to alternating Clad+LDAC and Aza showed promising remission rates of 57% in pts with ND AML having TP53 mut/loss and high rates of MRD negativity in responders; median RFS and OS was not reached at 9 mos follow-up. Five pts (36% overall, and 50% of the responders) could be consolidated with HSCT, with none of them relapsing after HSCT. The trial continues to accrue pts."

Clinical • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • TP53

Phase II study of cladribine, low-dose cytarabine, and venetoclax, alternating with azacitidine and venetoclax, in higher-risk chronic myelomonocytic leukemia and myelodysplastic syndromes. (ASCO 2025) - P2 | "CDA, LDAC and VEN is safe in pts with HR-MDS and CMML, demonstrating promising results in ND pts."

P2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • TP53

Impact of NPM1 co-mutation on outcomes in RAS-mutated Acute Myeloid Leukemia (ASH 2025) - "RAS mutations in AML have been recently shown to impart an intermediate prognostic risk when treated with hypomethylating agents (HMA) + venetoclax and may benefit from high-dose cytarabine consolidation in pts treated with intensive chemotherapy (IC)...Comparison within different treatment groups shows that pts treated with low-intensity chemotherapy (Low-IC) [Cladribine+LDAC or HMA] without Venetoclax (Ven) had a median OS of 17.9 months (CI 3.8–46.6) vs. 7.2 months (CI 4.8–10.02; p = 0.04) for RAS -mut/ NPM1 -mut vs. RAS -mut/ NPM1 -wt, respectively... The prognostic impact of RAS mutations in AML is modified in the setting of NPM 1 co-mutations. Pts with RAS -mutated AML without co-occurring NPM1 mutations had significantly inferior OS and EFS than those with RAS- mut/ NPM1- mut. Low-IC and IC alone showed a clear survival benefit for RAS -mut/ NPM1 -mut compared to RAS -mut/ NPM1 -wt."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • HRAS • KMT2A • KRAS • NPM1 • NRAS • RAS

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

Myeloablative fractionated busulfan, fludarabine, cladribine, thiotepa, and venetoclax (Cladillac) conditioning for high-risk AML: A phase 2 trial (ASH 2025) - P2/3 | "To reduce GVHD-associated morbidity and mortality, weincorporated post-transplant cyclophosphamide (PTCy)...GVHD prophylaxis consisted of PTCy 50mg/kg on days +3 and +4, tacrolimus ± mycophenolate mofetil... This study met its primary endpoint, demonstrating a promising 3-year PFS of 58% in acohort of patients with very high-risk AML. Outcomes were particularly favorable in TP53 wild-typepatients, with a low relapse rate of 13% and 3-year OS of 74%. These findings support furtherinvestigation of this novel conditioning regimen."

P2 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • FLT3 • TP53

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. (PubMed, J Clin Oncol) - "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."

Journal • P2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases

Myelodysplasia-Related Mutation Clearance Is Associated With Improved Outcomes in Newly Diagnosed Acute Myeloid Leukemia Treated With Low-Intensity Therapy (SOHO 2026) - "Most (92%) received LIT plus venetoclax; 57% received HMA-based therapy and 43% received cladribine/low-dose cytarabine–based therapy. MRM clearance at CR/CRi in LIT-treated newly diagnosed AML correlated with improved survival outcomes, including in patients who were FCM MRD-negative, and can be used as an MRD marker. AML: acute myeloid leukemia, ASXL1: ASXL transcriptional regulator 1, BCOR: BCL6 corepressor, CR: complete response, CRi: complete response with incomplete count recovery, ELN: European LeukemiaNet, EZH2: enhancer of zeste 2 polycomb repressive complex 2 subunit, FCM: flow cytometry, FLT3-ITD: fms-like tyrosine kinase 3 gene internal tandem duplication, HMA: hypomethylating agent, HR: hazard ratio, HSCT: hematopoietic stem cell transplantation, IQR: interquartile range, LIT: low-intensity therapy, MRD: measurable residual disease, MRM: myelodysplasia-related gene mutation, NPM1: nucleophosmin 1, NR: not reached, OS: overall survival, RAS: rat sarcoma..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Sarcoma • Solid Tumor • ASXL1 • BCL6 • BCOR • EZH2 • FLT3 • NPM1 • RUNX1 • SF3B1 • SRSF2 • STAG2 • TP53 • U2AF1 • ZRSR2