pentostatin / Generic mfg. - 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

Live imaging of human xenogeneic CART cells in a clinical trial of companion dogs with lymphoma (ASH 2025) - "First, we tested and optimized a chemotherapy regimen to achieve optimal lymphodepletion in dogs.Healthy beagles were treated with pentostatin (pen) on days 2-4 (0.125, 0.25, or 0.5 mg/kg i.v.),cyclophosphamide (cy) on day 4 (400 mg/m2 i.v.), or combination cy/pen. In summary, this study demonstrated that xenogeneic CART cells were well-tolerated, induced remission,and were visualized via PET imaging in companion dogs with lymphoma. These results are promising bothfor the treatment of companion dogs with novel cell therapies and for the translation of novel CART celltherapies into human clinical trials."

CAR T-Cell Therapy • Clinical • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • B2M • HLA-C

Venetoclax-based therapies in patients with Relapsed/Refractory T-cell prolymphocytic leukemia (ASH 2025) - "The median number of prior lines of therapy before VEN initiation was 1(range, 1–5); 19 pts (54%) were treated with VEN-based therapy in 1st salvage while 16 pts (46%) weretreated in 2nd or later salvage.VEN was combined with cladribine (+/- additional agents) in 17 pts (49%), including 8 (23%) who alsoreceived ruxolitinib. Nine pts (26%) were treated with VEN and pentostatin (+/- alemtuzumab), 3 (9%) withFCM (fludarabine, cyclophosphamide, mitoxantrone), 2 (6%) with alemtuzumab alone, 2 (6%) withruxolitinib alone, and 1 (3%) each with bendamustine or as monotherapy... Pts with R/R T-PLL continue to face poor prognosis. VEN-based therapies demonstrateencouraging response rates in this refractory, proliferative, heavily pretreated population, with improvedsurvival observed among responders and those with longer duration of 1st remission. However, OSremains short, highlighting the need for prospective trials to optimize VEN-based treatment and postremission strategies in..."

Clinical • IO biomarker • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Prolymphocytic Leukemia • Thrombocytopenia • JAK1 • JAK3 • STAT5B

Phase 2 trial of cladribine plus immediate rituximab for 1st-line treatment of hairy cell leukemia – long term follow-up of original and additional patient cohorts (ASH 2025) - "Itresponds well to purine analogs cladribine (CDA) and pentostatin, but minimal residual disease (MRD)and relapses are common. First-line CDAR is highly effective for HCL, achieving MRD-free CR in 54/59 (92%) total patientsat 6 months and 55/59 (93%) long term. The high MRD-free CR rate may be due to synergy of cladribineand rituximab starting the same day. Transient appearance of MRD which later resolved may be relatedto immune destruction."

Clinical • P2 data • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Thrombocytopenia

Impact of pre-transplant bone marrow cellularity and fibrosis on post-transplant outcomes in sickle cell disease (ASH 2025) - P1/2 | "All patients received alemtuzumab and TBI with post-HCT cyclophosphamide; some received additional pre-conditioning with pentostatin andcyclophosphamide. Our initial data suggest that neither baseline cellularity nor fibrosis significantly impacted HCT outcomes.Interestingly, all patients with fibrosis ratings > 2 demonstrated graft failure. Further, we observe thatbaseline cellularity is associated with the presence of DDR mutations before HCT. We will expand to ournon-myeloablative matched-sibling HCT cohort, increasing our overall study sample size and moredefinitively assessing the impact of baseline cellularity and fibrosis values on HCT outcomes and CH.Further studies are indicated to evaluate whether increased erythropoietic stress is associated with anincreased prevalence of baseline DDR-CH."

Post-transplantation • Pre-transplantation • Fibrosis • Genetic Disorders • Hematological Disorders • Immunology • Sickle Cell Disease • Transplant Rejection • Transplantation

Assessment of minimal residual disease with droplet digital polymerase chain reaction for BRAF V600E mutation in patients with hairy cell leukemia treated with purine analogs (ASH 2025) - "As frontline therapy, 31/35 patients (89%) receiveda single course of cladribine 0.14 mg/kg/daily for 5 days subcutaneously, 4/35 (11%) received pentostatinevery 15 days for 8 doses. In this study including 35 HCL patients treated with purine analogs frontline, we found that14% achieved an undetectable MRD. More importantly, we demonstrated that the clearance of BRAFmutation was associated with a better long-term outcome."

Clinical • Minimal residual disease • Polymerase Chain Reaction • Residual disease • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • B2M • BRAF

Pentostatin/TBI conditioning for allogeneic transplantation in T-cell lymphomas (ASH 2025) - "While most reduced-intensity conditioning regimens rely on fludarabine, pentostatin is a purine analog with a distinctmechanism of action and a favorable immunosuppressive profile that supports donor engraftment withreduced toxicity...All patients received calcineurin inhibitor–based GVHD prophylaxis,and 12% also received post-transplant cyclophosphamide... This 20-year institutional experience demonstrates that pentostatin and TBI is a well-tolerated and effective reduced-intensity conditioning platform for allogeneic transplant in T-celllymphomas. The regimen was associated with full engraftment, low early mortality, and a 5-year OS of49%—a result that compares favorably to published outcomes in this historically high-risk population.Notably, over 32% of patients underwent transplant not in remission and still experienced meaningfullong-term survival, suggesting this regimen offers GVL efficacy even in chemoresistant disease. Theseresults support the continued use and..."

Acute Graft versus Host Disease • Adult T-Cell Leukemia-Lymphoma • Chronic Graft versus Host Disease • Cutaneous T-cell Lymphoma • Dermatology • Extranodal Natural Killer/T-cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Hepatosplenic T-cell Lymphoma • Immunology • Infectious Disease • Leukemia • Lymphoma • Mycosis Fungoides • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • Prolymphocytic Leukemia • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • Transplantation • ALK • CD4 • CD8

Impact of ruxolitinib on corticosteroid treatment patterns in 1147 patients with chronic graft-versus-host disease in real-world practice in the United States: A long-term follow-up analysis (ASH 2025) - "Prescription refills in pharmacy claim records wereused to determine RUX and prednisone-equivalent CS dosing and treatment length. Line of therapy forcGVHD medications was based on claims for CS, belumosudil, abatacept, alemtuzumab, RUX, etanercept,hydroxychloroquine, ibrutinib, imatinib, interleukin-2, methotrexate, mycophenolate mofetil, pentostatin,and rituximab after cGVHD diagnosis... Patients treated with RUX for cGVHD in real-world clinical practice remained on treatmentfor a median of 8 months; 40.9% remained on RUX for 1 year and 21.3% for 2 years, suggesting long-termpersistence of safety and ongoing clinical benefit. Median time from earliest CS fill for cGVHD todiscontinuation or reduction to low-dose CS was 77 days. By the end of 1-year follow-up, 90% of patientsachieved discontinuation or reduction to low-dose CS."

Clinical • Real-world • Real-world evidence • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • IL2

Real-Life Efficacy and Safety of Vemurafenib Plus Rituximab (V+R) in Relapsed or Refractory Hairy Cell Leukemia: A Multi-Center Retrospective Study (HCL-PG03R) (ASH 2023) - "Prior therapies (median 2; range 0-11) included chemotherapy with cladribine or pentostatin (94% of pts), interferon-alpha (29%), rituximab (31%), splenectomy (6%), BRAF inhibitor monotherapy (6%) and zanubrutinib (3%). Analysis of MRD by allele-specific PCR for BRAF-V600E in the bone marrow aspirate was performed in 30 pts and showed MRD clearance (<0.05% mutant alleles) at a high rate: 79% (22/28 CR pts; or 65%, 22/35 pts, by ITT), which raised to 82% (66% by ITT) when including 1 additional CR case untested by PCR which had negative bone marrow flow cytometry.At a median follow-up of 21 months after the end of treatment, RFS was high among the 31 responding pts, with just 1 relapse (3%) in the only case obtaining a PR post-therapy (Figure). CONCLUSIONSThis study validates in a real-life context the high efficacy and tolerability of the V+R chemo-free regimen delivered to R/R HCL pts, including the cost-saving use of biosimilar rituximab."

Retrospective data • Dermatology • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Leukemia • Musculoskeletal Pain • Oncology • Respiratory Diseases • Tuberculosis

Serum Soluble Interleukin-2 Receptor Levels in Hairy Cell Leukemia As a Marker of Tumor Burden with Prognostic Value and As a Tool for Disease Monitoring (ASH 2023) - "Among treated patients, 47/54 (87%) received cladribine and 7/54 (13%) pentostatin...A similar decrease in sIL-2R levels after therapy was observed in 4 relapsed patients treated with rituximab-vemurafenib (median pre-therapy sIL-2R 11.460 vs. 467 kU/L after treatment, p = 0.03; median reduction 10.848 kU/L)...While more data is required to validate its use in clinical routine, sIL-2R could be used as an effective marker for disease monitoring. Moreover, given the prognostic significance of post-therapy levels, sIL-2R may represent a prognostic factor alongside MRD to identify those patients that are more likely to develop early relapse."

IO biomarker • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD38 • IL2

Maintenance Low-Dose BRAF Inhibition and Rituximab in Relapsed Hairy Cell Leukemia: A Therapeutic Alternative. (PubMed, Cureus) - "Purine analogs such as cladribine and pentostatin have been the mainstay of treatment for HCL. Despite high responsiveness to first-line therapy with purine analogs, almost half of the patients with HCL relapse and become progressively resistant to these medications. Treatment with a combination of BRAF V600E inhibitor and anti-CD20 monoclonal antibody has achieved durable responses in relapsed HCL. Here, we present a patient with relapsed and refractory HCL who achieved only partial response with three months of treatment with high-dose vemurafenib and rituximab, following which he was maintained on low-dose vemurafenib plus monthly rituximab for almost a year, after which he achieved complete morphologic and molecular response."

Journal • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Biosynthesis and genome mining strategies for purine-derived N-nucleoside antibiotics. (PubMed, Front Microbiol) - "Understanding the biosynthesis and genetic organization of N-NAs not only sheds light on their structural diversity but also provides a framework for genome mining. Specific subclasses such as pentostatin-, angustmycin-, and deazapurine-type compounds exhibit Structure-Activity relationships that could guide the rational design and genome-based discovery of new nucleoside antibiotics."

Journal • Review

Enhancer regulator MLL4 controls skeletal muscle metabolic efficiency by limiting AMPK-mediated fuel catabolism. (PubMed, Nat Commun) - "Pharmacologic inhibition of AMP-metabolizing pathway by Pentostatin activates muscle AMPK, confers resistance to obesity and improves metabolic health. These findings identify an enhancer regulator limiting AMPK-mediated muscle fuel catabolism, offering a potential strategy for treating obesity-related disorders."

Journal • Genetic Disorders • Hematological Malignancies • Leukemia • Obesity • Oncology • AMPK • KMT2D

Survival and Therapeutic Outcomes in T-Cell Prolymphocytic Leukemia (T-PLL): A Collaborative Multi-Center Study Cohort (ASH 2024) - "Other active second-line treatments included : pentostatin (n=23; 44% ORR, 17% CR), ruxolitinib-based regimens (n=4; 25% ORR, 0% CR), venetoclax-based regimens (n=13; 39% ORR, 8% CR), bendamustine (n=10; 30% ORR, 0% CR), and nelarabine (n=4; 75% ORR, 50% CR)...Conclusions : In this large, multi-center study of T-PLL, frontline treatment with a combination of alemtuzumab/pentostatin improved response rates and OS...Intriguingly, TCL1A+, and CD4- T- PLL had worse OS/PFS, and scRNAseq confirmed unique molecular signatures in these populations, suggesting these represent novel molecular subtypes of T-PLL with prognostic significance. These studies form the foundation for future, targeted, therapeutic studies in this rare, aggressive disease with few treatment options."

Clinical • Hematological Malignancies • Leukemia • Oncology • Prolymphocytic Leukemia • CD4 • CD8 • TCL1A

Adenosine deaminase loss leads to purine metabolism dysfunction, senescence and reduced DNA repair mechanisms in sALS astrocytes (ALS-MND 2025) - "Senescence and DNA damage analysis were performed under physiological conditions and under purine stress conditions using the ADA inhibitor pentostatin.Results : We found that levels of CD73 and hypoxanthineguanine phosphoribosyltransferase two key purine metabolism enzymes were reduced in SALS iAstrocytes at the mRNA and protein level...SALS iAstrocytes showed purine metabolism dysfunction including reduced purine salvage and an altered senescent phenotype, which was reflected in the biofluid samples and motor cortex of SALS cases. ADA inhibition exacerbated this phenotype and resulted in astrocytes being more susceptible to adenosine induced DNA damage. Loss of ADA resulted in less 53BP1 mediated DNA repair in SALS iAstrocytes, which was mimicked in controls by ADA inhibition."

Metabolic Disorders • CD73 • CDKN1A • TP53 • TP53BP1

Real-World Evaluation of T-Prolymphocytic Leukemia Outcomes Using the 2019 T-PLL International Study Group Criteria (ASH 2023) - "Introduction: T-Cell Prolymphocytic Leukemia (T-PLL) is a rare, aggressive T-cell malignancy with very poor prognosis. No substantial differences in T-PLL response rates or survival were observed when using the TPLL-ISG criteria when compared to historical reports. Patients who had a CR or CRi to alemtuzumab that proceeded with allo-SCT had a significantly prolonged OS and PFS. Patients with CD4-CD8+ T-PLL had inferior survival , but this will need to be validated in a larger sample set."

Clinical • HEOR • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Prolymphocytic Leukemia • CD4 • CD8 • TCL1A

Predictors of Outcome for Allogeneic Stem Cell Transplantation with a Reduced Intensity Pentostatin/TBI Conditioning Regimen in T-Cell Lymphomas: A Single Center Experience (ASH 2023) - "In patients with TCL, RIC for alloSCT was well tolerated and compared favorably with retrospective data from larger groups of patients from CIBMTR and EBMT who were transplanted with different regimens2. Interestingly, transplant-related outcomes were similar for patients with CR vs partial response (PR) at the time of transplant, and outcomes were better in patients younger than 65. Relapsed patients had a poor outcome despite salvage therapy with only a 30% OS at 3 years."

Biomarker • Clinical • Acute Graft versus Host Disease • Adult T-Cell Leukemia-Lymphoma • Bone Marrow Transplantation • Chronic Graft versus Host Disease • CNS Disorders • Cytomegalovirus Infection • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Prolymphocytic Leukemia • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • Transplantation

Pentostatin Low-Dose TBI Is an Effective Conditioning Regimen That Permits Donor Engraftment in Patients with High Co-Morbidities Undergoing the First Transplant or Prior to a Second Transplant (ASH 2024) - "GvHD prophylaxis was reduced-dose post-transplant cyclophosphamide on days +3 and +4 (25 mg/m2, rPTCy) with 6 months of therapeutic levels of either sirolimus or tacrolimus and twice daily mycophenolate to day 35...Clinical outcomes were compared to similar patients receiving a Fludarabine and Melphalan (140 mg/m2) reduced intensity conditioning regimen who received full-dose PTCy (50 mg/m2 x 2 doses)...Pento/TBI conditioning with rPTCy is a promising approach appropriate for patients with significant co-morbidities undergoing first allogeneic transplant or patients who require a second or third transplant following primary graft failure/rejection or relapse. The kinetics of immune reconstitution based on serial blood mononuclear cells collected post-transplant will be presented."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Myelofibrosis • Oncology • Sickle Cell Disease • T Cell Non-Hodgkin Lymphoma • Transplant Rejection • Transplantation • CD34

Role of Bruton Tyrosine Kinase Inhibitors (BTKi) in Relapsed Refractory (r/r) Hairy Cell Leukaemia Patients: A Single-Centre Real-World Data Set from the Royal Marsden Hospital (ASH 2024) - "Purine analogues (PA) such as pentostatin are highly effective in cHCL, however 36-44% of patients relapse post PA and require further treatment 2...4/7 (57%) were treated with Ibrutinib, 3/7 (43%) were treated with Zanubrutinib...There is a critical need to collect further real-world data on BTKi in the r/r setting due to dismal outcomes in this patient group. Furthermore, BTKi should be evaluated in combination with other HCL-active agents in clinical trials."

Clinical • Real-world • Real-world evidence • Hairy Cell Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • BTK

Incidence of Second Primary Malignancies in Hairy Cell Leukemia: US Population-Based Study from 2000- 2021 (ASH 2024) - "Introduction : Hairy Cell Leukemia (HCL) is a rare B-cell lymphoproliferative disorder characterized by an indolent course but notable responsiveness to purine analog-based therapies such as cladribine and pentostatin. It stresses the need for tailored surveillance protocols and preventive measures in the light of heightened susceptibility to specific malignancies in the critical years following their initial diagnosis. Furthermore, our results advocate for ongoing research into the mechanisms behind SPM development in this population and emphasize the integration of comprehensive long-term survivorship care into the broader framework of oncological treatment strategies."

Clinical • Endocrine Cancer • Hairy Cell Leukemia • Hematological Malignancies • Hodgkin Lymphoma • Kidney Cancer • Leukemia • Lymphoma • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • Thyroid Gland Carcinoma

A Randomized Phase 2 Trial of 2nd-Line Cladribine with Concurrent or Delayed Rituximab in Patients with Classic Hairy Cell Leukemia (ASH 2024) - "Background : Hairy cell leukemia is a B-cell malignancy characterized by pancytopenia, splenomegaly, and long-term remissions to purine analogs cladribine (CDA) and pentostatin, but late relapses occur, presumably from minimal residual disease (MRD)...Two after CDAR vs 4 after CDA (p=0.42) progressed and required alternative therapy, several of whom remain MRD-free after moxetumomab pasudotox with rituximab...Thus, CDA with delayed rituximab at >6 months if/when blood becomes MRD-positive is still reasonable 2nd line treatment of HCL. Delayed rituximab is now being tested to eliminate MRD in patients who achieve MRD-positive CR to MEK +/- BRAF inhibition."

Clinical • P2 data • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Oncology

ASSESSING THE IMPACT OF COMORBIDITIES IN HAIRY CELL LEUKEMIA: VALIDATION OF THE CLL-CI/TRES SCORE IN PATIENTS TREATED WITH PURINE ANALOGUES (SIE 2025) - "Hairy cell leukemia (HCL) is an indolent disease that enjoys excellent response and durable remissions after therapy with the purine analogues (PAs) cladribine (2CDA) and pentostatin (DCF). The inability to demonstrate different outcomes between intermediate and high-risk patients was likely due to the low number of patients and events in the latter group. Overall, the TRES score could be a viable tool to assess comorbidities and aid in selecting/developing more tolerable therapeutic strategies for higher risk patients, thus deserving further validation in a larger cohort."

Clinical • Chronic Lymphocytic Leukemia • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma

Phase 2 trial of rituximab with either pentostatin or bendamustine for multiply relapsed or refractory hairy cell leukemia. (PubMed, Blood) - P2 | "Possible DCFR superiority was hypothesis-generating, given uneven baseline risks and trial design. NCT01059786."

Journal • P2 data • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Oncology

Threading through the data for chemotherapy-free alternatives in the treatment of hairy cell leukemia. (PubMed, Leuk Lymphoma) - "While agents such as cladribine and pentostatin remain standard front-line therapies, their long-term toxicities-particularly myelosuppression and immune dysfunction-have led to growing interest in chemotherapy-free agents...In this review, we summarize existing and emerging treatment strategies for HCL, including BRAF and MEK inhibitors, Bruton tyrosine kinase (BTK) inhibitors, anti-CD20 monoclonal antibodies, and venetoclax. These approaches offer therapeutic promise for patients with relapsed/refractory disease and for those ineligible to receive traditional chemotherapy. These regimens also result in high rates of minimal residual disease (MRD) negativity, potentially bringing us closer to the cure for HCL."

Journal • Review • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Oncology

Efficacy of Adding Venetoclax to Chemoimmunotherapy in Patients With Relapsed/ Refractory T-Cell Prolymphocytic Leukemia (SOHO 2025) - "Eleven pts received alemtuzumab, venetoclax ± purine analogs (cladribine or pentostatin), with 2 also receiving ruxolitinib; 13 pts received purine analogs, venetoclax ± ruxolitinib; and 9 pts received other regimens. The incorporation of targeted agents such as venetoclax may lead to deeper remissions and prolonged response durations in R/R T-PLL. The potential benefit of adding venetoclax to chemoimmunotherapy warrants evaluation in prospective trials."

Clinical • Hematological Malignancies • Leukemia • Oncology • Prolymphocytic Leukemia