Metformin alleviates side effects and supports the resumption of interferon therapy in polycythemia vera and essential thrombocythemia

Interferon-α is emerging as the preferential cytoreductive therapy for polycythemia vera (PV) and essential thrombocythemia (ET) due to improved long-term outcomes over alternatives such as hydroxyurea. Historically, interferon-α therapy has been marked by high rates of adverse events and subsequently poor adherence. Long-acting formulations of interferon-α, i.e., ropeginterferon-α-2b (ropeg), improve tolerability. However, nearly half of ropeg-treated patients experience fatigue, arthralgias, or myalgias and 10-20% discontinue treatment or cannot tolerate maximal ropeg doses, due to adverse events. Herein, we report our retrospective experience of adjunct metformin therapy in 11 PV and ET patients who were intolerant of ropeg. Metformin improved ropeg-related fatigue and/or myalgias in 10 of 11 patients. A complete hematologic response (CHR) was maintained in all 6 patients who had already achieved this prior to starting metformin, and a deepened hematologic response was observed in 3 of 4 patients after the addition of metformin. These encouraging results merit further evaluation in a randomized clinical study. Further, additional investigations are needed to elucidate the mechanism of interferon-α-mediated fatigue and myalgias and the mechanism of putative beneficial interaction between interferon-α and metformin.