The study enrolled 35 patients with relapsed or refractory Hodgkin's or non-Hodgkin's lymphoma of any type except Burkitt's or CNS lymphoma. Patients had relapsed following a median of five prior therapies (range 2-15); 44% had failed prior stem cell transplant and 52% were rituximab refractory.
Thirty-four patients received daily doses of pacritinib for a 28-day each cycle of doses ranging from 100 to 600 mg/day. The maximum tolerated dose was not reached. Pacritinib inhibited JAK2 signaling at all dosing levels and FLT-3 inhibition were seen in most patients. The median time on study drug was 88 days (range of one to574) with six patients on pacritinib for longer than six months and 17 patients for longer than three months. There were three partial responses (greater than or equal to 300 mg/d) (2 mantle cell; 1 indolent NHL); 15 patients achieved stable disease. Seven of 13 patients with stable disease had tumor reductions ranging from 4% to 46% of baseline target lesions. Treatment was well tolerated, with mostly grade 1-2 toxicities. Gastrointestinal toxicities were the most frequent (32%) with no grade 3-4 side effects reported even among the 12 patients treated at the highest dose (600mg/d). Cytopenias were infrequent and modest supporting the lack of myelosupression with pacritinib therapy even among a patient population with poor baseline marrow reserve. The authors concluded, "collectively our data demonstrate that SB1518 is well tolerated in patients with relapsed lymphoma and has promising activity. The data warrant further efficacy studies of JAK/STAT pathway inhibitors either alone or in combination regimens."
The publication by Younes, et al. titled "Phase I Study of a Novel Oral Janus Kinase 2 Inhibitor, SB1518, in Patients with Relapsed Lymphoma: Evidence of Clinical and Biologic Activity in Multiple Lymphoma Subtypes," is available at http://jco.ascopubs.org/content/early/recent.
About Janus Associated Kinase (JAK)The JAK family of enzymes are a central component in signal transduction pathways, which are critical to normal blood cell growth and development as well as inflammatory cytokine expression and immune responses. When dysregulated by activating mutations, uncontrolled blood cell growth can occur accompanied by inflammation and immune system activation contributing to disease manifestations in MPN. Autoimmune diseases such as psoriasis and rheumatoid arthritis also have activation of this pathway and JAK inhibitors are in development for these disorders.