Pancreatic cancer is the third leading cause of cancer related death and by 2030, it will be second only to lung cancer. We have seen tremendous advances in therapies for lung cancer as well as other solid tumors using a molecular targeted approach but our progress in treating pancreatic cancer has been incremental with median overall survival remaining less than one year. There is an urgent need for improved therapies with better efficacy and less toxicity. Small molecule inhibitors, monoclonal antibodies and immune modulatory therapies have been used. Here we review the progress that we have made with these targeted therapies.

Philadelphia (Ph)‐like acute lymphoblastic leukemia (ALL) is associated with a poor response to standard chemotherapy. However, outcomes with novel antibody and cellular therapies in relapsed/refractory (r/r) Ph‐like ALL are largely unknown. We conducted a single‐center retrospective analysis of adult patients (n = 96) with r/r B‐ALL and fusions associated with Ph‐like who received novel salvage therapies. Patients were treated with 149 individual novel regimens (blinatumomab = 83, inotuzumab ozogamicin [InO] = 36, and CD19CAR T cells = 30). The median age at first novel salvage therapy was 36 years (range; 18–71). Ph‐like fusions were IGH::CRLF2 (n = 48), P2RY8::CRLF2 (n = 26), JAK2 (n = 9), ABL‐class (n = 8), EPOR::IGH (n = 4) and ETV6::NTRK2 (n = 1). CD19CAR T cells were administered later in the course of therapy compared to blinatumomab and InO (p < .001) and more frequently in recipients who relapsed after allogeneic hematopoietic cell transplantation (alloHCT) (p = .002). Blinatumomab was administered at an older age compared to InO and CAR T‐cells (p = .004). The complete remission (CR)/CR with incomplete hematologic recovery (CRi) rates were 63%, 72%, and 90% following blinatumomab, InO and CD19CAR, respectively, among which 50%, 50%, and 44% of responders underwent consolidation with alloHCT, respectively. In multivariable analysis, the type of novel therapy (p = .044) and pretreatment marrow blasts (p = .006) predicted the CR/CRi rate, while the Ph‐like fusion subtype (p = .016), pretreatment marrow blasts (p = .022) and post‐response consolidation with alloHCT (p < .001) influenced event‐free survival. In conclusion, novel therapies are effective in inducing high remission rates in patients with r/r Ph‐like ALL and successfully transitioning the responders to alloHCT.

Rearrangements of lysine [K] methyltransferase 2 A (KMT2A) gene, previously known as the MLL gene, occur in 3 to 7% of adult patients with de novo AML and are enriched in therapy-related disease, p...

The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.

The accurate diagnosis and classification of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) are challenging due to the overlapping pathological and molecular features of myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). We investigated the genomic landscape in different MDS/MPN subtypes, including chronic myelomonocytic leukemia (CMML; n = 97), atypical chronic myeloid leukemia (aCML; n = 8), MDS/MPN-unclassified (MDS/MPN-U; n = 44), and MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n = 12). Our study indicated that MDS/MPN is characterized by mutations commonly identified in myeloid neoplasms, with TET2 (52%) being the most frequently mutated gene, followed by ASXL1 (38.7%), SRSF2 (34.7%), and JAK2 (19.7%), among others. However, the distribution of recurrent mutations differs across the MDS/MPN subtypes. We confirmed that specific gene combinations correlate with specific MDS/MPN subtypes (e.g., TET2/SRSF2 in CMML, ASXL1/SETBP1 in aCML, and SF3B1/JAK2 in MDS/MPN-RS-T), with MDS/MPN-U being the most heterogeneous. Furthermore, we found that older age (≥65 years) and mutations in RUNX1 and TP53 were associated with poorer clinical outcomes in CMML (p < 0.05) by multivariate analysis. 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.