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Anti‐myeloma potential of ruxolitinib in co‐existing JAK2V617F‐positive smouldering myeloma and polycythaemia vera

Myeloproliferative neoplasms (MPNs) and plasma cell disorders (PCDs) are clonal diseases of the myeloid and lymphoid lineages, respectively. JAK2V617F, a characteristic somatic mutation found in the myeloid lineages of Philadelphia-negative (Ph-negative) MPNs (Baxter et al., 2005), has been identified in rare cases of acute myeloid leukaemia, myelodysplastic syndrome, chronic myelomonocytic leukaemia, and Ph-negative chronic myeloid leukaemia (CML) (Levine et al., 2005; Scott et al., 2005). By contrast in lymphoid malignancies, JAK2V617F was not found in the corresponding lymphoid cells (Levine et al., 2005; Melzner et al., 2006). In PCDs, peripheral blood cluster of differentiation (CD) 19 + CD11b+CD34 + cells from 93 patients with myeloma did not identify the JAK2V617F variant (Fiorini et al., 2006). Patients with co-existing PCD and either Ph-positive CML (Nitta et al., 1999) or Ph-negative MPN have been reported (Economopoulos et al., 1989; Fink et al., 1993; Kuroda et al., 2008; Malhotra et al., 2014; Le Clech et al., 2017; Marchetti et al., 2018; Katerji & Hudson, 2018; Bouchla et al., 2019), and it has been described that the presence of monoclonal protein at diagnosis of MPN is associated with worse prognosis (Le Clech et al., 2017). However, in these studies the presence of JAK2V617F in plasma cells has not been described. In a case of concurrent essential thrombocythaemia and multiple myeloma, for example, JAK2V617F was decidedly absent from bone marrow-derived plasma cells (Kuroda et al., 2008). We report two cases of JAK2V617F-positive PV who developed smouldering myeloma. Bone marrow plasma cells were positive for JAK2V617F. On treatment with ruxolitinib, both patients had myeloma haematological response.