Leukemia & Lymphoma最新文献

FDA approved agents for the treatment of chronic GVHD including ruxolitinib and belumosudil are effective steroid-sparing agents, with overall response rates (ORR) of 76% and 65% respectively. Ruxolitinib and belumosudil are well tolerated with different primary targets. Little data is available on the use of combination ruxolitinib and belumosudil. This is a single center, retrospective analysis of 20 treatment-refractory patients with chronic GVHD treated with combination ruxolitinib and belumosudil. The ORR including complete response (CR) and partial response (PR) at any time was 55% (11/20). Among responding patients, other immunosuppressive agents were tapered or discontinued in all patients. None of the patients developed EBV or CMV reactivation requiring treatment. 4 patients (20%) developed pneumonia and 2 patients (10%) developed viral URI. Cytopenias were not exacerbated. No patients had graft failure or relapsed disease. The combination is tolerable, delays the need for alternative therapies, and facilitates tapering of corticosteroids.

The importance of extra-nodal disease has been well recognized in follicular lymphoma, and is incorporated into various prognostic tools. However, the optimal treatment strategy for this subgroup remains unclear. In this multicenter retrospective study, we analyzed 143 patients who received either R-CHOP or Bendamustine-Rituximab (BR), with a median follow-up of 69.7 months. Our findings indicate that extra-nodal disease confers poorer PFS (5-year PFS 58% vs 66%, p = 0.03) while high-risk relapse predict poorer OS (5-year OS 56% vs 94%, p < 0.001). Subgroup analysis on 98 patients with extra-nodal disease revealed that BR induction conferred superior PFS compared to R-CHOP (HR 0.49, p = 0.032) while maintenance rituximab also improved PFS (HR 0.44, p = 0.033). Patients who received R-CHOP without maintenance rituximab had significantly worse PFS (5-year PFS 41% vs 68%, p = 0.005) and OS (5-year OS 83% vs 100%, p = 0.007) compared to those with maintenance rituximab. Role of maintenance rituximab post BR remained unclear. In this retrospective study of follicular lymphoma patients with extra-nodal disease, BR induction yielded favorable PFS compared to R-CHOP and could be a preferred treatment approach. Maintenance rituximab after R-CHOP significantly improve PFS and OS and should be considered in all appropriate patients.

For older unfit patients receiving venetoclax-based induction, data on the significance of interim bone marrow biopies (BMBx) findings on clinical outcomes is lacking. We retrospectively evaluated interim BMBx results performed on Cycle 1 days 21-28 of venetoclax-based therapy in 69 adults with myeloid malignancies to determine whether blast clearance was associated with overall survival (OS) and overall response rate (ORR). Median age was 75 years (range 69-78). Results demonstrated blast reduction (BR, <5% blasts) in 71%. Venetoclax was held to allow count recovery in 86% of these patients. Achieving interim BMBx BR was significantly associated with OS (p = 0.0033) and ORR (Cohen's kappa 0.39). Patients whose venetoclax was held experienced low rates of infection and reduced cytopenias. These findings support the importance of cycle 1 BMBx assessment during venetoclax-based therapies, specifically in predicting which patients will achieve optimal outcomes and in mitigating toxicity.

Overactivation of the Transforming Growth Factor Beta (TGF-β) pathway is implicated in the pathogenesis of cytopenias in Myelodysplastic syndromes (MDS) and Acute Myeloid Leukemia (AML). IOA-359 and IOA-360 are potent small molecule inhibitors of the TGF-beta Receptor type I kinase (TGF-βRI, also referred to as ALK5, activin receptor-like kinase 5) that abrogate SMAD phosphorylation in hematopoietic cell lines. Both inhibitors were able to inhibit TGF-β mediated gene transcription at specific doses. ALK5 inhibitors abrogated the growth inhibitory effects of TGF-β on healthy hematopoietic stem cells and stimulated hematopoietic differentiation in cell lines and MDS/AML specimens. These data demonstrate preclinical efficacy of two novel ALK5 inhibitors, IOA-359 and IOA-360, in stimulating erythroid differentiation in MDS and AML.

Mutations in the NOTCH1 oncogene are recurrently linked to chronic lymphocytic leukemia (CLL), found in approximately 10% of CLL cases at diagnosis. Although these mutations are associated with clinical outcomes, their significance in the context of treatment with anti-CD20 monoclonal antibodies, Bruton's tyrosine kinase inhibitors, and BCL2 inhibitors remains controversial. Consequently, testing for NOTCH1 mutations is not recommended outside of a clinical setting. This systematic literature review aims to consolidate the current understanding that NOTCH1 mutations are exploratory and not recommended for routine clinical practice.