Myelodysplastic Syndrome

P1/2, N=25, Not yet recruiting, Thomas Jefferson University

P=N/A, N=30, Recruiting, Groupe Hospitalier de la Region de Mulhouse et Sud Alsace | Not yet recruiting --> Recruiting

This allogeneic CAR T product demonstrated acceptable safety and preliminary anti-leukemic activity. ClinicalTrials.gov: NCT05984199.

Given the well-documented association between SF3B1 mutations and MECOM rearrangements, analysis of MECOM expression and RNA sequencing (RNA-seq) is crucial for SF3B1-mutated patients, even in the absence of elevated blast counts. Furthermore, this case underscores the need for further research into the synergistic biological role of spliceosome mutations and MECOM rearrangements in driving leukemia.

There were no significant differences in time to blast transformation or time to next treatment depending on PHF6 gene status. According to the results of most studies published to date (SR), PHF6MUT has a prognostic role in MNs; our results are consistent in terms of clinical outcomes, but these marginal effects should be interpreted with caution in the context of existing prognostic models given the limitations of the small sample size.

P1, N=78, Not yet recruiting, Genmab

P1/2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=80 --> 30

P=N/A, N=2115, Completed, National Heart, Lung, and Blood Institute (NHLBI) | N=3500 --> 2115 | Trial completion date: Aug 2025 --> Dec 2025 | Active, not recruiting --> Completed

P1/2, N=160, Completed, Taiho Oncology, Inc. | Active, not recruiting --> Completed

P=N/A, N=300, Recruiting, Chinese University of Hong Kong | N=150 --> 300 | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2028

P1, N=18, Recruiting, Pamela Munster | Trial completion date: Feb 2027 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

The DNA hypomethylating agents (HMAs) 5-azacitidine and decitabine are the backbone of disease modifying therapy in myelodysplastic syndromes (MDS). We show that pyrimethamine, an FDA-approved antifolate, induces apoptosis across leukemic models, synergizes with venetoclax, and restores sensitivity in HMA- and venetoclax-resistant leukemia. Pyrimethamine promotes differentiation of stem and progenitor cells in primary MDS samples and in combination with venetoclax directly inhibits pyrimidine synthesis, revealing a clinically actionable strategy to overcome a key mechanism of therapeutic resistance.