Chronic Myelomonocytic Leukemia

P1/2, N=34, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=58 --> 34

This cytokine inhibited the proliferation of WT but not CMML hematopoietic stem and progenitor cells (HSPCs) in which CXCL8 receptors were downregulated. CXCL8 receptor inhibitors and CXCL8 blockade restored WT HSPC proliferation, suggesting that relieving CXCL8 selective pressure on WT HSPCs is a potential strategy to slow CMML progression and restore some healthy hematopoiesis.

Aging boosts inflammatory genes upregulation, whereas MDS favors antigen presentation, reflecting distinct immune and disease-specific adaptations. • MDS shows reduced inflammatory activity in CD14+ cells, whereas CMML exhibits heightened inflammation, highlighting distinct disease mechanisms.

P1, N=63, Active, not recruiting, NextCure, Inc. | Recruiting --> Active, not recruiting

P=N/A, N=40, Not yet recruiting, The Seventh Affiliated Hospital, Sun Yat-sen University; The Seventh Affiliated Hospital, Sun Yat-sen University

Introduction – We previously reported the efficacy and safety results of a combination of ibrutinib with rituximab in patients (pts) with mantle cell lymphoma (MCL) ≥ 65 years. Conclusions – Chemotherapy-free frontline therapy with AR is highly effective, safe, induces deep MRD negative responses and alters immune landscape in older pts with MCL. Randomized studies are needed to confirm whether this regimen can be the new first line standard treatment for older MCL patients.

The patient with NEMO deficiency demonstrated JMML-like manifestation and severe inflammation. PBMCs of the patient demonstrated increased RAS signaling activation with unknown pathophysiology.

P2/3, N=317, Active, not recruiting, Taiho Oncology, Inc. | Recruiting --> Active, not recruiting

P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025

P1/2, N=52, Recruiting, Uma Borate | Not yet recruiting --> Recruiting

No abstract available

P3, N=454, Completed, Takeda | Active, not recruiting --> Completed

P3, N=530, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

For future development, molecular testing will likely include whole genome and transcriptome sequencing, and primarily molecular classifications of myeloid neoplasms have already been suggested. As such, genetically defined groups should still constitute the basis for our understanding of disease development from early onset to progression, while clinicopathological features could then be used to describe the stage of the disease rather than the specific type of myeloid neoplasm.

P3, N=170, Recruiting, ImmuneOnco Biopharmaceuticals (Shanghai) Inc.

Epoetin alfa was used simultaneously in 31 patients (60.7%). The effect was particularly high in the IPSS-M low and very low groups. We believe that the relatively high response rate in our patients was influenced by the frequent use of a higher dose (1.75 mg/kg) and especially by adding ESA to luspatercept in poorly responding patients.

This study on reclassification of VUS in blood cancers demonstrated that one in seven VUS were re-classified 12 months post initial classification. This can inform practice guidelines and potentially impact the prognosis, diagnosis and treatment of haematological malignancies.

Mutations in spliceosomal components have been identified in numerous cancer subtypes, with mutations in RNA binding proteins SF3B1, SRSF2, U2AF1, and ZRSR2 occurring frequently in AML and in up to 60% of patients with MDS, as well as in chronic myelomonocytic leukaemia and in 10% of patients with chronic lymphocytic leukaemia. In this review, we explore therapeutic strategies targeting aberrant splicing and the potential of these approaches to drive clinical responses.

P2, N=63, Recruiting, Thomas Jefferson University | Trial completion date: Oct 2024 --> Apr 2025 | Trial primary completion date: Oct 2024 --> Apr 2025

P2, N=29, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Sep 2024 --> Sep 2025

P2, N=55, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed

P1, N=36, Recruiting, Kahr Medical | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Aug 2024 --> Jun 2025

The genetic profile of these mutCFN CMML patients closely resembled that of AML, with higher-risk clinical characteristics. Our findings lead us to suggest including the assessment of these mutations in CMML prognostic models and treating these patients with AML-type therapies, including intensive chemotherapy and allogeneic stem cell transplantation, whenever feasible, and consider certain targeted therapies approved for use in AML.

P2, N=170, Active, not recruiting, St. Jude Children's Research Hospital | Recruiting --> Active, not recruiting | N=52 --> 170

P2, N=25, Not yet recruiting, Case Comprehensive Cancer Center

Therefore, we describe a case of a patient diagnosed with CMML NPM1mut and briefly review the literature to highlight the uncertainty about how to classify a CMML with NPM1 mutation. We emphasize the importance of a comprehensive molecular study, which is crucial to optimize the individualized treatment of patients, enabling them to access targeted therapies.

Our study revealed the clinical and genetic characteristics of patients with myeloid neoplasms harboring rare and non-cryptic NUP98r. Given its association with poor prognosis, a comprehensive evaluation is crucial for identifying previously underdiagnosed NUP98r in patients with myeloid neoplasms.

In MDS/MPN-U, CBL mutations (p < 0.05) were the sole negative prognostic factors identified in our study by multivariate analysis (p < 0.05). Overall, our study provides genetic insights into various MDS/MPN subtypes, which may aid in diagnosis and clinical decision-making for patients with MDS/MPN.

After an initial response to antimetabolite therapy (6-mercaptopurine), she underwent haploidentical hematopoietic stem cell transplantation (HSCT) and is currently in complete remission. The goal of this review is to gain insight into the various hematological diseases associated with NS, starting from our unique case.

The specific molecular signatures sustained their significant predictive performance in the context of the CMML-specific molecular prognostic model (CPSS-mol). PHF6MUT identifies a unique subset of patients with CMML characterized by thrombocytopenia, higher prevalence of LoY, and superior prognosis.

P2, N=60, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2025 --> Dec 2025

P=N/A, N=60, Recruiting, Nantes University Hospital | Not yet recruiting --> Recruiting | Initiation date: Jun 2024 --> Sep 2024 | Trial primary completion date: Apr 2026 --> Jul 2026

P1/2, N=17, Active, not recruiting, Stanford University | Recruiting --> Active, not recruiting | N=48 --> 17 | Trial completion date: Aug 2024 --> Apr 2025 | Trial primary completion date: Aug 2024 --> Jan 2025

P1, N=36, Recruiting, Children's Oncology Group | Trial completion date: Apr 2026 --> Jun 2026 | Trial primary completion date: Apr 2026 --> Jun 2026

Steroid treatment led to improvement, but coincided with a surge in white cell count (WCC), prompting an urgent haematological review.Subsequent investigations, including a punch biopsy of the external ear and a bone marrow biopsy revealed BPDCN concurrent with chronic myelomonocytic leukaemia. This case highlights the challenging diagnostic journey, emphasising the need for multidisciplinary collaboration and the potential for unique BPDCN presentations, expanding our understanding of this malignancy.

Since 2017, twelve agents have been approved for the treatment of AML subsets: the BCL2 inhibitor venetoclax; the CD33 antibody drug conjugate gemtuzumab ozogamicin; three FLT3 inhibitors (midostaurin, gilteritinib, quizartinib); three IDH inhibitors (ivosidenib and olutasidenib targeting IDH1 mutations; enasidenib targeting IDH2 mutations); two oral hypomethylating agents (oral poorly absorbable azacitidine; fully absorbable decitabine-cedazuridine [latter approved as an alternative to parenteral hypomethylating agents in myelodysplastic syndrome and chronic myelomonocytic leukemia but commonly used in AML]); and CPX-351 (encapsulated liposomal 5:1 molar ratio of cytarabine and daunorubicin), and glasdegib (hedgehog inhibitor)...To achieve optimal results in such a rare and heterogeneous entity as AML requires expertise, familiarity with this rare cancer, and the access to, and delivery of disparate therapies under rigorous supportive care conditions. In this review, we update the standard-of-care and investigational therapies and outline promising current and future research directions.

Other etiologies of renal injury associated with clonal monocytosis include direct renal infiltration by monocytes, renal extramedullary hematopoiesis, myeloproliferative neoplasm-associated glomerulopathy, auto-immune (membranous nephropathy, minimal change disease) and paraneoplastic manifestations, thrombotic microangiopathy, obstructive nephropathy due to myeloproliferation, and urate nephropathy due to tumor lysis syndrome. We propose to group these mechanistic etiologies of renal injury as clonal monocytosis of renal significance and provide guidance on their diagnosis and management.

Furthermore, we noted an increased percentage of CMML CD34+ stem and progenitor cells expressing CD116 and CD131 in all CBL mutant cases and increased CD116 receptor density compared to healthy controls, similar to CMML overall. In summary, our data demonstrate that CBL mutations are associated with distinct molecular and clinical features in CMML and are potentially targetable with CD116-directed immunotherapy.

P2, N=235, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

The safety profile was broadly consistent with other published PRMT5 inhibitor studies. ClinicalTrials.gov: NCT03614728.

P1/2, N=63, Terminated, Nerviano Medical Sciences | N=200 --> 63 | Trial completion date: Feb 2026 --> Aug 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Aug 2024; Study stopped due to strategic reasons. The decision is not based on specific safety findings as the safety observed in the phase II part of the study is in line with what was reported in the phase I part.

P1, N=75, Recruiting, Epigenetix, Inc. | N=50 --> 75 | Trial completion date: Sep 2024 --> May 2025 | Trial primary completion date: Jun 2024 --> May 2025