Pretransplant MRD detection of fusion transcripts is strongly prognostic in KMT2A-rearranged acute myeloid leukemia.

Pretransplant detection of KMT2Ar measurable residual disease ≥0.001% by quantitative polymerase chain reaction was associated with significantly inferior posttransplant survival (2-year relapse-free survival 17% vs 59%; P = .001) and increased 2-year cumulative incidence of relapse (75% vs 25%, P = .

Phase Ib study of sabatolimab (MBG453), a novel immunotherapy targeting TIM-3 antibody, in combination with decitabine or azacitidine in high- or very high-risk myelodysplastic syndromes.

The safety and efficacy of sabatolimab, a novel immunotherapy targeting T-cell immunoglobulin domain and mucin domain-3 (TIM-3), was assessed in combination with hypomethylating agents (HMAs) in patients with HMA-naive revised International Prognostic System Score (IPSS-R) high- or very high-risk myelodysplastic syndromes (HR/vHR-MDS) or chronic myelomonocytic leukemia (CMML). Sabatolimab + HMA had a safety profile similar to that reported for HMA alone and demonstrated durable clinical responses in patients with HR/vHR-MDS. These results support the ongoing evaluation of sabatolimab-based combination therapy in MDS, CMML, and acute myeloid leukemia.

Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML: a randomized, placebo-controlled study by the ALLG.

Sorafenib maintenance improves outcomes after hematopoietic cell transplant (HCT) for patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML). Although promising outcomes have been reported for sorafenib plus intensive chemotherapy, randomized data are limited. This placebo-controlled, phase 2 study (ACTRN12611001112954) randomized 102 patients (aged 18-65 years) 2:1 to sorafenib vs placebo (days 4-10) combined with intensive induction: idarubicin 12 mg/m2 on days 1 to 3 plus either cytarabine 1.

Molecular MRD is strongly prognostic in patients with NPM1-mutated AML receiving venetoclax-based nonintensive therapy.

Assessment of measurable residual disease (MRD) by quantitative reverse transcription polymerase chain reaction is strongly prognostic in patients with NPM1-mutated acute myeloid leukemia (AML) treated with intensive chemotherapy; however, there are no data regarding its utility in venetoclax-based nonintensive therapy, despite high efficacy in this genotype. We analyzed the prognostic impact of NPM1 MRD in an international real-world cohort of 76 previously untreated patients with NPM1-mutated AML who achieved complete remission (CR)/CR with incomplete hematological recovery following treatment with venetoclax and hypomethylating agents (HMAs) or low-dose cytarabine (LDAC). A total of 44 patients (58%) achieved bone marrow (BM) MRD negativity, and a further 14 (18%) achieved a reduction of ≥4 log10 from baseline as their best response, with no difference between HMAs and LDAC.

Targeting Measurable Residual Disease (MRD) in Acute Myeloid Leukemia (AML): Moving beyond Prognostication.

Measurable residual disease (MRD) assessment in acute myeloid leukemia (AML) has an established role in disease prognostication, particularly in guiding decisions for hematopoietic cell transplantation in first remission. Serial MRD assessment is now routinely recommended in the evaluation of treatment response and monitoring in AML by the European LeukemiaNet. The key question remains, however, if MRD in AML is clinically actionable or "does MRD merely portend fate"? With a series of new drug approvals since 2017, we now have more targeted and less toxic therapeutic options for the potential application of MRD-directed therapy.

Augmented ICE in Patients With Poor-Risk Refractory and Relapsed Lymphomas.

Background: In patients with relapsed/refractory lymphoma after first line therapy, chemosensitivity to salvage chemotherapy is the main determinant of outcome pre-autologous stem cell transplant . With novel therapies not yet widely available and poor responses to conventional dose salvage therapy such as ifosfamide, carboplatin, and etoposide (ICE) in patients with early relapse within 12 months and primary refractory disease, there is capacity to dose intensify ifosfamide and etoposide (augmented ICE).

Methods: We retrospectively evaluated patients who received augmented ICE between 2010 and 2020 and report on response, deliverability, toxicities, and outcome.

Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT): A Phase Ib Dose-Escalation Study of Venetoclax Combined With Modified Intensive Chemotherapy.

Purpose: The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax has an emerging role in acute myeloid leukemia (AML), with promising response rates in combination with hypomethylating agents or low-dose cytarabine in older patients. The tolerability and efficacy of venetoclax in combination with intensive chemotherapy in AML is unknown.

Patients And Methods: Patients with AML who were ≥ 65 years (≥ 60 years if monosomal karyotype) and fit for intensive chemotherapy were allocated to venetoclax dose-escalation cohorts (range, 50-600 mg).