Sorafenib and omacetaxine mepesuccinate as a safe and effective treatment for acute myeloid leukemia carrying internal tandem duplication of Fms-like tyrosine kinase 3.

BACKGROUND: Omacetaxine mepesuccinate (OME) has antileukemic effects against acute myeloid leukemia (AML) carrying an internal tandem duplication of Fms-like tyrosine kinase 3 (FLT3-ITD). A phase 2 clinical trial was conducted to evaluate a combination treatment of sorafenib and omacetaxine mepesuccinate (SOME). METHODS: Relapsed or refractory (R/R) or newly diagnosed patients were treated with sorafenib (200-400 mg twice daily) and OME (2 mg daily) for 7 (first course) or 5 days (second course onward) every 21 days until disease progression or allogeneic hematopoietic stem cell transplantation (HSCT). The primary endpoint was composite complete remission, which was defined as complete remission (CR) plus complete remission with incomplete hematologic recovery (CRi). Secondary endpoints were leukemia-free survival (LFS) and overall survival (OS). RESULTS: Thirty-nine R/R patients and 5 newly diagnosed patients were recruited. Among the R/R patients, 28 achieved CR or CRi. Two patients showed partial remission, and 9 patients did not respond. Among the 5 newly diagnosed patients, 4 achieved CR, and 1 achieved CRi. The median LFS and OS were 5.6 and 10.9 months, respectively. Prior Fms-like tyrosine kinase 3 (FLT3) inhibitor exposure (P = .007), 2 or more inductions (P = .001), and coexisting IDH2 (P = .008) and RUNX1 mutations (P = .003) were associated with lower CR/CRi rates. HSCT consolidation and deep molecular responses (defined as an FLT3-ITD variant allelic frequency [VAF] ≤ 0.1% or a nucleophosmin 1 [NPM1] mutant VAF ≤ 0.01%) were associated with better OS and LFS. Prior FLT3 inhibitor exposure and 2 or more inductions were associated with inferior LFS. CONCLUSIONS: SOME was safe and effective for R/R and newly diagnosed FLT3-ITD AML.

Low-dose pembrolizumab for relapsed/refractory Hodgkin lymphoma: high efficacy with minimal toxicity.

Five patients with refractory/relapsed classical Hodgkin lymphoma (cHL), four having failed multiple lines of chemotherapy and brentuximab vedotin, were treated with low-dose pembrolizumab (median dose 100 mg, range: 100-200 mg, every 3 weeks). Complete response (CR) was achieved in four patients (80%), after a median cumulative dose of merely 495 (300-800) milligrams. Three CR patients have continued to receive pembrolizumab for a median of 16 (14-25) cycles, remaining in CR for a median of 18 (9-18) months. One CR patient underwent autologous hematopoietic stem cell transplantation and has remained in CR for 9 months. Partial response (PR) was achieved in one patient (20%), after a cumulative dose of 400 mg. The overall response rate was therefore 100% (CR: 80%; PR: 20%). Toxicity was virtually absent, with only grade 1 diarrhea and eczema each observed in one patient. Low-dose pembrolizumab was highly efficacious, achieving responses with minimal toxicity and at much lower costs.