Impaired Hydroxylation of 5-Methylcytosine in TET2-Mutated Myeloid Malignancies
Through the use of 2 assays (1 developed specifically for this study), researchers demonstrated for the first time that TET2 mutations in predicted catalytic residues and other positions compromise TET2 function in patients with various myeloid malignancies. Follow - ing in vitro study, researchers used methylation arrays in 62 of the study’s 102 patients to analyze methylation patterns in patients with and without TET2 mutations, finding that an associated methylation signature was skewed strongly toward hypo methylation compared with hyper methylation. The researchers concluded that their results suggest that TET2 is involved in conversion of 5-methylcytosine to 5-hydroxymethylcytosine in DNA. Jankowska A, et al. Abstract 1.
Prophylactic Rituximab After ASCT Prevents Steroid-Requiring Chronic Graft-vs-Host Disease
In a phase 2 trial, rituximab at 3, 6, 9, and 12 months after allogeneic hema - topoietic stem cell transplantation reduced the rate of steroid-requir - ing chronic graft-versus-host disease (GVHD) in patients in remission with out active GVHD. At 1 year, researchers found that the cumulative incidence of chronic GVHD requiring corticosteroids was just more than half of historical levels at their institution. They also identified very low numbers of CD19+ B-cells during the first year after transplant, and that patients without chronic GVHD trended toward enhanced B-cell recovery. BRAF levels also trended higher in those without chronic GVHD as well as in those with chronic GVHD who did not require corticosteroid treatment. The re searchers concluded that these findings predict that this therapy could free patients from or reduce the severity of chronic GVHD, but cautioned a randomized trial should confirm their findings. Cutler C, et al. Abstract 214.
Brentuximab Vedotin (SGN-35) in Patients with Relapsed or Refractory Hodgkin Lymphoma
Brentuximab vedotin was observed to produce tumor shrinkage in 94% of 102 patients with relapsed or refractory Hodgkin lymphoma after autologous stem cell transplant. In a phase 2, single- arm study, this novel antibody– drug conjugate targeted to CD30 also produced an objective response rate of 75%, and a B symptom resolution rate of 83%. The agent was found to have a manageable adverse event profile. Because of the poor prognosis of these patients, the researchers concluded that their results encourage further study of brentuximab vedotin. Chen R, et al. Abstract 283.
Crizotinib in Advanced, Chemoresistant ALK-Positive Lymphoma Patients
This report on 2 chemoresistant patients with ALK-positive anaplastic large cell lymphoma suggests that this disease is sensitive to ALK inhibition, in these cases through treatment with crizotinib. This agent, a competitive small-molecule inhibitor of the ALK and c-Met/HGF receptor tyrosine kinases with cellular IC50 values in NPM-ALK expressing cells comprised between 24 and 60 nM, achieved regression of superficial adenopathies in both patients with 8 days of treatment. Patient 1 achieved complete response, which is ongoing at 6 months. Patient 2 continues complete response at 5 months of treatment. Gambacorti- Passerini CB, et al. Abstract 2877.