From: Emerging agents and regimens for polycythemia vera and essential thrombocythemia
Agent | Mechanism of action | Clinical data | Reference |
---|---|---|---|
Gandotinib | Pan-JAK inhibition | Phase 1 trial; N = 6 (median age 62.5 years) Results: 3 patients had clinic-hematologic partial response [31] Phase 2 trial; N = 20 Results: 4 patients (20%) had CR and 15 (75%) had PR, thus an ORR of 95% [32] | |
Ruxolitinib + PEG-IFN alfa-2a | JAK1/2 inhibition + immunomodulation/antiangiogenesis | Phase 2 trial; N = 32 (median age 57 years, 66% high-risk, 94% with prior interferon exposure) Results: 10 patients (31%) had remission with 3 (9%) in CR and another 7 (22%) with PR. Symptom burden was improved with only 6% drop-out rate. | [33] |
Ropeginterferon alfa-2b | Immunomodulation/antiangiogenesis | Phase 3 trial; N = 222 (median age 58–60 years) randomized to ropeginterferon alfa-2b Results: improved rates of composite CHR when compared with hydroxyurea (53% vs. 38%, p = 0.044) and improved symptom burden at 36 months follow-up | [34] |
Givinostat | Histone deacetylase inhibition | Phase 1b/2 trial; N = 47 Results: ORR of 81%, but significant toxicity (35–50% grade ≤ 3 diarrhea, thrombocytopenia and creatinine elevation) | [35] |
Idasanutlin | MDM2 inhibition | Phase 2 trial; N = 27 (median age 56 years, 26% with prior ruxolitinib exposure) Results: 9 patients (56%) achieved hematocrit control by 32 weeks of therapy, however significant gastrointestinal toxicity | [36] |
PTG-300 | Hepcidin mimesis | Phase 2 trial; N = 13, all requiring therapeutic phlebotomy (mean age 57.4 years, 46% high-risk) Interim data showing normalization of iron stores, 100% therapeutic phlebotomy-independence and improved symptom burden | [37] |