Real-World Evidence of Treatment-Free Remission Strategies and Outcomes in Chronic Myeloid Leukemia.

: Despite the remarkable efficacy of tyrosine kinase inhibitors (TKIs), patients with chronic myeloid leukemia (CML) often face adverse effects, prompting investigations into treatment-free remission (TFR) for patients with sustained deep responses. : Our objective was to assess real-world outcomes of TFR in a single-center cohort of patients in the southeastern U.S.

Momelotinib - a tale of trials, tribulations, transfusion independence, and triumph.

Introduction: Momelotinib is a small molecule inhibitor of JAK1, JAK2, and ACVR1 that is approved by the FDA and EMA for adults patients with intermediate/high risk myelofibrosis (MF) and anemia. Inhibition of the JAK-STAT pathway has a well-established role in MF therapy, producing reductions in MF-related symptoms and spleen size. Inhibition of ACVR1 downregulates hepcidin production and improves anemia.

Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Acute Myeloid Leukaemia.

Introduction: This phase 2 study evaluated magrolimab+venetoclax (VEN)+azacitidine (AZA) in untreated, unfit acute myeloid leukaemia (AML) and magrolimab+mitoxantrone+etoposide+cytarabine in relapsed/refractory (R/R) AML.

Methods: Endpoints included complete remission rate (CRR), overall response rate (ORR), overall survival (OS) and safety.

Results: Eighteen and 36 patients were enrolled into the unfit and R/R AML arms, respectively.

Outcomes With Venetoclax 50 mg, Hypomethylating Agents, and Voriconazole or Posaconazole in Acute Myeloid Leukemia.

Background: Real-world evidence for hypomethylating agent (HMA) + venetoclax 50 mg (VEN50) with voriconazole and posaconazole in acute myeloid leukemia (AML), is limited.

Methods: We evaluated outcomes of patients with newly-diagnosed AML treated with HMA + VEN50 with either posaconazole ( = 23) or voriconazole ( = 95).

Results: We report that treatment with HMA + VEN50 with either azole elicits a response rate similar to that described in the VIALE-A trial.

A phase I / IIa trial of PXS-5505, a novel pan-lysyl oxidase inhibitor, in advanced myelofibrosis.

Myelofibrosis (MF) is a progressive disease characterized by accumulation of extracellular matrix (ECM) in the bone marrow (BM) which impairs normal hematopoiesis. While Janus kinase (JAK) inhibitors reduce spleen volume and provide symptomatic improvement, they do not resolve BM fibrosis and may cause or exacerbate anemia and thrombocytopenia. An anti-fibrotic therapy capable of normalising BM microenvironment and function remains a significant gap in the current treatment landscape.

Patient-reported outcomes in Philadelphia chromosome-positive acute lymphoblastic leukemia patients treated with ponatinib or imatinib: results from the PhALLCON trial.

In the Phase 3 PhALLCON trial (NCT03589326), ponatinib demonstrated superior efficacy and comparable safety profile versus imatinib in adults with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Here we report patient-reported outcomes (PRO) from PhALLCON assessed as exploratory endpoints using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) and EQ-5D-5L. Primary PRO domains included FACT-G physical well-being, FACT-Leu subscale (FACT-LeuS), Trial Outcome Index (TOI), FACT-Leu total score, FACT-G total score, and EQ-5D visual analogue scale.

Quality-Adjusted Time Without Symptoms of Disease or Toxicity (Q-TWiST) in Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Comparison of Ponatinib Versus Imatinib.

Background: In the phase 3 ponatinib-3001 trial (PhALLCON, NCT03589326), ponatinib demonstrated superior efficacy over imatinib with comparable safety in patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). This post hoc analysis evaluated the net benefits of ponatinib using a quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) approach.

Methods: Overall survival (OS) time for patients from PhALLCON was partitioned into three health states: TOX (time with grade 3+ treatment-emergent adverse events [TEAEs] before disease progression), TWiST (time without toxicity before progression), and REL (time from progression until death or end of follow-up).

Real-world treatment patterns and health care resource use for patients with myelofibrosis: results from the METER study.

Myelofibrosis (MF), a myeloproliferative neoplasm, was most commonly treated with hydroxyurea (HU) before approval of ruxolitinib (RUX), now the standard of care. Factors that influence real-world MF treatment patterns are not well understood. The METER study was a multi-country, retrospective chart review of MF treatment patterns, treatment effectiveness, and health care resource utilization.

Investigational drugs in early phase trials for myelofibrosis.

Introduction: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, cytopenias, and organomegaly. Four JAK inhibitors are US-FDA approved for treatment of MF. While these drugs reduce symptom burden and spleen size to varying degrees, they do not affect the natural disease course or decrease the risk of leukemic transformation.

Ruxolitinib for myelofibrosis: The earlier, the better?

There is mounting evidence to support the use of ruxolitinib earlier in the disease course of MF. Use in intermediate-1 risk MF is generally associated with higher efficacy and lower toxicity.

Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults.

Background: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.

Methods: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with -negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.

Consistency of Spleen and Symptom Reduction Regardless of Cytopenia in Patients With Myelofibrosis Treated With Pacritinib.

Background: Pacritinib is a JAK2/IRAK1/ACVR1 inhibitor that is approved in the United States for the treatment of patients with myelofibrosis who have a platelet count < 50 × 109/L. Phase 3 clinical studies of pacritinib included patients across a wide range of baseline platelet and hemoglobin levels.

Patients And Methods: In order to assess the impact of baseline blood counts on pacritinib efficacy, an analysis of efficacy outcomes by baseline platelet and hemoglobin levels was performed using data pooled from 2 Phase 3 studies of pacritinib in patients with MF (PERSIST-1 and PERSIST-2).

Ponatinib vs Imatinib in Frontline Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial.

Importance: In newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), disease progression due to acquired resistance to first- or second-generation BCR::ABL1 tyrosine kinase inhibitors is common. Ponatinib inhibits BCR::ABL1 and all single-mutation variants, including T315I.

Objective: To compare frontline ponatinib vs imatinib in adults with newly diagnosed Ph+ ALL.

Safety and tolerability of AMG 330 in adults with relapsed/refractory AML: a phase 1a dose-escalation study.

AMG 330, a bispecific T-cell engager (BiTE®) that binds CD33 and CD3 on T cells facilitates T-cell-mediated cytotoxicity against CD33+ cells. This first-in-human, open-label, dose-escalation study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AMG 330 in adults with relapsed/refractory acute myeloid leukemia (R/R AML). Amongst 77 patients treated with AMG 330 (0.

A novel application of XPO1 inhibition for the treatment of myelofibrosis.

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by constitutional symptoms, progressive cytopenias, and splenomegaly. Activating mutations in the JAK/STAT pathway and cytokine dysregulation driving bone marrow fibrosis and extramedullary hematopoiesis underlie the pathobiology of MF. Although multiple JAK inhibitors are currently approved and provide significant symptom improvement, these agents do not possess disease course modifying potential.

Addition of single dose gemtuzumab ozogamicin to intensive induction chemotherapy in core-binding factor acute myeloid leukemia.

In a meta-analysis of 5 trials, the addition of gemtuzumab ozogamicin (GO) to intensive induction chemotherapy led to a survival benefit in patients with core-binding factor (CBF) acute myeloid leukemia (AML). Given the heterogeneous incorporation of GO in clinical trials, the ideal dose and schedule remains unclear. We conducted a single-center retrospective analysis to compare outcomes of patients with CBF-AML treated with intensive induction chemotherapy, with or without a single dose of GO 3 mg/m, during induction only.

Interferons in the treatment of myeloproliferative neoplasms.

Interferons are cytokines with immunomodulatory properties and disease-modifying effects that have been used to treat myeloproliferative neoplasms (MPNs) for more than 35 years. The initial use of interferons was limited due to difficulties with administration and a significant toxicity profile. Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule.

SOHO State of the Art Updates and Next Questions | Diagnosis, Outcomes, and Management of Prefibrotic Myelofibrosis.

Prefibrotic primary myelofibrosis (prefibrotic PMF) is a myeloproliferative neoplasm with distinct characteristics comprising histopathological and clinico-biological parameters. It is classified as a subtype of primary myelofibrosis. In clinical practice, it is essential to correctly distinguish prefibrotic PMF from essential thrombocythemia especially but also overt PMF besides other myeloid neoplasms.

Avapritinib versus Placebo in Indolent Systemic Mastocytosis.

BACKGROUND: Indolent systemic mastocytosis (ISM) is a clonal mast-cell disease driven by the KIT D816V mutation. We assessed the efficacy and safety of avapritinib versus placebo, both with best supportive care, in patients with ISM. METHODS: We randomized patients with moderate to severe ISM (total symptom score [TSS] of ≥28; scores range from 0 to 110, with higher numbers indicating more severe symptoms) two to one to avapritinib 25 mg once daily (n=141) or placebo (n=71).