Leukemia
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Jun 01 – Jun 08, 2026
Dynamic genetic and nongenetic RAS pathway activation drives resistance to FLT3 and BCL2 inhibitor therapy.
BLOOD · Q1 JOURNAL - RANK #2/98TOP-TIER
This Phase 1b trial of combined venetoclax (BCL2 inhibitor) and gilteritinib (FLT3 inhibitor) in patients with acute myeloid leukemia aimed to characterize mechanisms of resistance. They used multiomic single-cell DNA/protein and RNA/protein profiling to analyze malignant clones and transcriptional states. While venetoclax and gilteritinib therapy eliminated FLT3-mutant clones, diverse RAS-activating events emerged, including selection for RAS mutations, non-mutational upregulation of RAS pathways, and a phenotypic switch to monocytic AML. RAS pathway inhibition restored sensitivity to venetoclax/gilteritinib, suggesting a potent therapeutic strategy against acquired resistance.
10.1182/blood.2025032466
Dual epitope anti-LILRB4 synthetic T-cell receptor and antigen receptor (STAR)-T-cell therapy for relapsed/refractory acute myeloid leukemia.
SIGNAL TRANSDUCT TAR · Q1 JOURNAL - RANK #1/319TOP-TIER
This first-in-human, prospective clinical trial (NCT05548088) evaluated dual-epitope nanobody-based anti-LILRB4 synthetic T-cell receptor and antigen receptor (STAR) T-cell therapy in nine adults with relapsed/refractory LILRB4-positive acute myeloid leukemia. Patients received a single infusion of autologous STAR-T cells and were followed for a median of 10.7 months; six patients were evaluable for safety and efficacy. No grade ≥3 cytokine release syndrome or ICANS occurred, although three patients died from documented infections. The best overall response rate was 50 % (3/6) in the efficacy set and 33.3 % in the full cohort, with on-treatment expansion of LILRB4-targeted STAR-T cells and reduction of LILRB4-positive blasts; single-cell RNA-seq suggested monocyte-mediated T-cell suppression in nonresponders.
10.1038/s41392-026-02765-7
May 18 – May 25, 2026
CRISPR-Cas9 CD33-deleted allogeneic hematopoietic cell transplantation with gemtuzumab ozogamicin maintenance in AML: a phase 1/2 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This multicenter phase 1/2a open-label trial evaluated trem-cel, a CRISPR-Cas9 gene-edited allogeneic hematopoietic cell transplantation (HCT) product lacking CD33, followed by gemtuzumab ozogamicin (GO) maintenance in 30 high-risk AML/MDS patients. The primary endpoint was neutrophil engraftment by day 28, which was achieved in all patients, with a median engraftment time of 10 days (95% CI: 9-10). Nineteen patients received GO maintenance, which was tolerated up to 2 mg/m² without prolonged high-grade cytopenias, though three cases of transplant-related mortality occurred. The trial concluded that trem-cel enabled safe engraftment and GO maintenance without prolonged hematologic toxicity.
10.1038/s41591-026-04362-1
Integration of venetoclax into a fludarabine and melphalan conditioning regimen in patients aged 50 years and older with acute myeloid leukemia and myelodysplastic syndrome: Results from a phase 2 clinical trial.
CANCER-AM CANCER SOC · Q1 JOURNAL - RANK #68/326
This phase 2 multicenter clinical trial evaluated a venetoclax, fludarabine, and melphalan (VFM) conditioning regimen for allogeneic hematopoietic stem cell transplantation in 60 patients aged 50–66 years with acute myeloid leukemia or myelodysplastic syndrome. The primary endpoint of 2-year disease-free survival was 75.0% (95% CI, 64.8%–86.8%), with 2-year overall survival of 78.3% (95% CI, 68.6%–89.5%) and relapse rate of 11.7% (95% CI, 5.1%–21.3%). Grade 2–3 nonhematologic adverse events occurred in 58% of patients, with no grade 4–5 toxicities; cumulative incidence of grade 2–4 acute graft-versus-host disease at day 100 was 5.0%. The authors concluded that VFM conditioning is feasible in older adults, with low rates of graft-versus-host disease and relapse supporting further study.
10.1002/cncr.70467
May 11 – May 18, 2026
A venetoclax-cytarabine-based induction regimen incorporating a translation inhibitor for adult patients with de novo acute myeloid leukemia.
CANCER-AM CANCER SOC · Q1 JOURNAL - RANK #68/326
This multicenter, open-label, single-arm prospective trial in China evaluated the efficacy and safety of a venetoclax–cytarabine-based induction regimen plus a clinically available translation inhibitor in adults with newly diagnosed AML. Fifty-two patients (median age 48.5; 27% poor risk) were treated; after one cycle, the overall response rate was 90% (95% CI 79–97) with 46 achieving composite complete remission. With median follow-up of 816 days (IQR 418–1143), estimated 1-year overall and event-free survival were both 81% (95% CI 71–92); immune profiling showed decreases in CD4 naive, CD8 naive, Th2, CD19+ cells and increases in CD4 TEM, Th1, NK cells with a higher Th1/Th2 ratio, plus reduced bone marrow IL-10. The regimen appeared effective and well-tolerated in young adults with de novo AML, warranting randomized trials (ChiCTR2100048208).
10.1002/cncr.70432
May 04 – May 11, 2026
Rosuvastatin enhances the efficacy of venetoclax-azacitidine in older acute myeloid leukemia patients via reducing T-cell exhaustion.
CANCER IMMUNOL IMMUN · Q1 JOURNAL - RANK #68/326
This multicenter phase II clinical trial (ChiCTR 2500111931) evaluated the efficacy and safety of adding rosuvastatin to venetoclax-azacitidine in older/unfit AML patients, achieving a complete response (CR) rate of 55.5% and a composite complete remission (CRc) rate of 72.2%, with 84.6% of CRc patients attaining MRD < 10. Median overall survival (OS) and relapse-free survival (RFS) were 18 and 14 months, respectively, and flow cytometry showed significant reductions in PD-1⁺CD4⁺ T cells (p=0.0137) and PD-1⁺CD8⁺ T cells (p=0.0277). The study concluded that rosuvastatin enhances T-cell cytotoxicity and reduces exhaustion, supporting further investigation of this triple regimen.
10.1007/s00262-026-04397-w
Apr 27 – May 04, 2026
Final results of nilotinib versus nilotinib combined with pegylated interferon alfa-2a as first-line therapy in chronic phase chronic myeloid leukaemia in France (PETALs): an open-label, multicentre, randomised phase 3 trial.
LANCET HAEMATOL · Q1 JOURNAL - RANK #3/98TOP-TIER
This open-label, multicentre, randomised phase 3 trial evaluated the efficacy and safety of nilotinib alone versus nilotinib combined with pegylated interferon alfa-2a as first-line therapy in newly diagnosed chronic phase chronic myeloid leukaemia (CP-CML) patients in France. Two hundred patients aged 18–65 were randomly assigned to nilotinib monotherapy or combination therapy, stratified by disease risk indices, with the primary endpoint being the cumulative rate of molecular response 4.5 (MR4.5) at 12 months. The combination group achieved a significantly higher MR4.5 rate (24% [95% CI 16.0–34.1]) compared to nilotinib alone (15% [8.6–24.2], p=0.048), but with comparable grade 3–4 haematological toxicities and notable psychiatric events. The study concludes enhanced initial deep molecular response with combination therapy, warranting further investigation of long-term outcomes.
10.1016/S2352-3026(26)00043-8
Distinct in vivo dynamics of donor-derived stem cell memory CAR T cells post-allogeneic HSCT relapse.
CELL · Q1 JOURNAL - RANK #3/319TOP-TIER
This first-in-human study (NCT01087294) investigates the dynamics, efficacy, and safety profile of donor-derived CAR-modified stem-cell memory T (TSCM) cells for B cell malignancies relapsing after allogeneic hematopoietic stem cell transplantation. Through a comparative assessment, TSCM cells demonstrated superior expansion, persistence, and reconstitution of the stem-like compartment over time compared to standard CAR T cells, achieving complete responses at lower doses without lymphodepletion. Mild cytokine-release syndrome was observed, dominated by IFN-γ, with tumor- and host-related factors contributing to resistance against TSCM cells. The study concludes that CAR TSCM cells are a promising platform for the development of next-generation CAR T cell therapies targeting relapsed B cell malignancies.
10.1016/j.cell.2026.03.047
Apr 13 – Apr 20, 2026
Inhibition of high CXCR4 with Motixafortide and absence of single-cell MRD predict outcome after AML consolidation.
BLOOD · Q1 JOURNAL - RANK #2/98TOP-TIER
This randomized, double-blind, placebo-controlled phase II trial (NCT02502968) investigated whether adding the CXCR4 antagonist Motixafortide to high-dose cytarabine (HiDAC) consolidation therapy improved outcomes for 128 patients with acute myeloid leukemia (AML) in first remission. The primary finding was that median relapse-free survival (RFS) did not differ significantly between groups (10.3 months for Motixafortide vs. 11.5 months for placebo; log-rank p=0.98), but biomarker analysis revealed that higher CXCR4 expression was associated with increased relapse risk in the placebo group (p=0.02) and reduced relapse rate in the Motixafortide group (p=0.047). Exploratory analyses also identified single-cell minimal residual disease (scMRD) levels predictive of inferior overall survival. The authors concluded that combining functional MRD profiling with biomarker-driven selection, such as by CXCR4 expression, may enable more precise post-remission interventions in AML.
10.1182/blood.2025032033
Apr 06 – Apr 13, 2026
A phase I, single-arm, open-label, dose-escalation, multicenter study of SAR445419, an off-the-shelf, ex vivo expanded allogeneic natural killer cell product, in participants with relapsed or refractory acute myeloid leukemia.
CANCER IMMUNOL IMMUN · Q1 JOURNAL - RANK #68/326
This multicenter, Phase 1, open-label, dose-escalation study evaluated the safety, tolerability, and feasibility of SAR445419, an allogeneic NK cell therapy, in adults with relapsed or refractory acute myeloid leukemia. Seven participants were enrolled and six received the therapy, with no dose-limiting toxicities observed. All participants experienced grade 3 anemia and grade 4 thrombocytopenia or neutropenia, five died from progression of AML, and no clinical responses were reported. The study was terminated early for reasons unrelated to safety or efficacy, supporting the concept of off-the-shelf NK cell therapy while highlighting the need for further investigation to enhance clinical efficacy.
10.1007/s00262-026-04333-y
Selinexor and Venetoclax Combination in Patients With Relapsed or Refractory Acute Myeloid Leukemia.
AM J HEMATOL · Q1 JOURNAL - RANK #10/98
This investigator-sponsored, open-label phase Ib trial (NCT03955783) prospectively evaluated selinexor plus venetoclax in adults with relapsed/refractory acute myeloid leukemia, establishing selinexor 80 mg weekly plus venetoclax 400 mg/day after ramp-up as the recommended phase II dose and assessing responses per IWG2003 and ELN 2022 criteria. Nineteen patients (median age 67.2 years; median 3 prior lines) were treated; common grade 3–5 adverse events included anemia (39%), neutropenia (33%), febrile neutropenia (28%), and thrombocytopenia (28%). The overall response rate was 21%, including two complete remissions (11%) with durations of 7 and 9.1 months; median event-free survival was 2.4 months (95% CI 1.9–12.1) and median overall survival was 6.4 months (95% CI 2.5–12.1) after a median follow-up of 3.0 months. The authors concluded the regimen was feasible and active without new safety signals, though overall survival remained poor.
10.1002/ajh.70266
Does stringent cytoreduction improve survival in advanced proliferative chronic myelomonocytic leukemia?
LEUKEMIA · Q1 JOURNAL - RANK #20/326TOP-TIER
This study investigated whether controlling myeloproliferation improves survival in advanced proliferative chronic myelomonocytic leukemia (CMML) by enrolling 120 patients randomized to decitabine (n=63) or hydroxyurea (n=57) (NCT02214407). The methodology included evaluating white blood cells, circulating monocytes, flow-defined classical monocytes (cMo), and immature granulocytes (iGRAN) after three and six treatment cycles using bone marrow aspiration and complete blood count. Key findings showed that persistent elevated monocytes or WBC after six cycles increased risk of death (HR=5.38, p=0.0003), and patients with cMo ≤ 0.94 ×10 /L and iGRAN ≤ 0.40 ×10 /L had a median OS of 35.1 vs. 15.3 months (p=0.013). The authors conclude that these biomarkers may predict CMML prognosis independently of treatment.
10.1038/s41375-026-02901-w
Phase 1 Study of KITE-222, an Autologous CLL-1-directed CAR T-cell Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
The primary objective of this Phase 1 prospective clinical trial was to evaluate the safety and efficacy of KITE-222, an autologous CLL-1-directed CAR T-cell therapy in patients with relapsed/refractory acute myeloid leukemia. Patients received escalating doses of CAR T-cells, with safety endpoints including dose-limiting toxicities (DLTs) and secondary endpoints assessing remission rate, adverse events, and pharmacokinetics/pharmacodynamics; twelve patients were treated across three cohorts. One DLT occurred (prolonged Grade 4 neutropenia/thrombocytopenia), all patients had Grade ≥3 adverse events, but clinically meaningful responses were not observed, although CLL-1+ blasts were depleted in some patients from Cohort 3. The principal conclusion is that KITE-222 demonstrated acceptable safety but lacked preliminary efficacy, indicating the need for future studies to address CLL-1 heterogeneity and improve antitumor activity.
10.1158/1078-0432.CCR-25-3745