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This Week in NEJM: Mar 1, 2012

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In NEJM this week, a team of European researchers reports its assessment of JAK inhibitor ruxolitinib versus the best available therapy for the treatment of myelofibrosis, a form of chronic leukemia. The team assigned 219 myelofibrosis patients to receive either ruxolitinib or the best available therapy, and found that 28 percent of the patients in the ruxolitinib group had at least a 35 percent reduction in spleen volume, compared to 0 percent in the best available treatment group. "At 48 weeks, the mean palpable spleen length had decreased by 56% with ruxolitinib but had increased by 4% with the best available therapy," the authors write. "The median duration of response with ruxolitinib was not reached, with 80% of patients still having a response at a median follow-up of 12 months." Patients in the ruxolitinib group also reported an improved quality of life, the team adds.

Also in NEJM this week, researchers from the US, Canada, and Australia report their own assessment of ruxolitinib for the treatment of myelofibrosis. This team randomly assigned 309 myelofibrosis patients to receive either ruxolitinib or placebo, and found that the primary end point of 35 percent reduction in spleen volume at 24 weeks was reached by 41.9 percent of the patients in the ruxolitinib group, compared to 0.7 percent of patients in the placebo group. "Ruxolitinib, as compared with placebo, provided significant clinical benefits in patients with myelofibrosis by reducing spleen size, ameliorating debilitating myelofibrosis-related symptoms, and improving overall survival," the authors write.

In a related editorial in NEJM this week, the Mayo Clinic's Ayalew Tefferi says that although these two studies — which were the basis for FDA's approval of ruxolitinib in intermediate-2 and high-risk myelofibrosis — showed a partial response in splenomegaly and alleviation of symptoms, they did not show "histopathologic, cytogenetic, or molecular remissions, and the drug was more likely to cause anemia and thrombocytopenia than to correct them." Further, Tefferi adds, the drug was not associated with a survival advantage over best available therapy. The drug's lack of anti-tumor activity "is probably a reflection of both the uncertain pathogenetic contribution of mutant JAK2 in myelofibrosis and the drug's suboptimal target specificity," Tefferi says. "Transient palliation of symptoms should not be confused with the primary goal of molecularly targeted cancer therapy, which is to eradicate or suppress the neoplastic clone."

The Scan

Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

In Nature Genetics, a Wellcome Sanger Institute-led team found that APOBEC1 may contribute to the development of the SBS2 and SBS13 mutational signatures in the small intestine.

Family Genetic Risk Score Linked to Diagnostic Trajectory in Psychiatric Disorders

Researchers in JAMA Psychiatry find ties between high or low family genetic risk scores and diagnostic stability or change in four major psychiatric disorders over time.

Study Questions Existence of Fetal Microbiome

A study appearing in Nature this week suggests that the reported fetal microbiome might be the result of sample contamination.

Fruit Fly Study Explores Gut Microbiome Effects on Circadian Rhythm

With gut microbiome and gene expression experiments, researchers in PNAS see signs that the microbiome contributes to circadian rhythm synchronicity and stability in fruit flies.