Plasma cell leukemia (PCL) is a rare and very aggressive form of plasma cell dyscrasia. In particular, secondary PCL (sPCL) shows poor prognosis and standard treatments remain lacking. We report herein two cases of patients with sPCL treated with elotuzumab, pomalidomide and dexamethasone (EPd) or isatuximab, pomalidomide and ­dexamethasone (IsaPd). After 2 cycles of IsaPd, stringent complete response (sCR) was seen in one patient, who is continuing to receive treatment while maintaining sCR. The other patient continued EPd for 8 cycles until progressive disease (PD) developed. Plasma cells in peripheral blood disappeared immediately, and best response was very good partial response. He was treated with 2 cycles of daratumumab, bortezomib and dexamethasone, then 3 cycles of IsaPd after PD again developed. These cases suggest that among the many novel agents that have been used against multiple myeloma, pomalidomide appears relatively effective for PCL. Further, administration of elotuzumab or isatuximab may provide additional effects to pomalidomide in the treatment of PCL. These therapies may represent effective options for the control of PCL, including sPCL, which has previously shown dismal prognosis.

The serine/threonine kinase TAK1 is constitutively overexpressed and auto-phosphorylated in multiple myeloma (MM) cells. Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase which dephosphorylates proteins phosphorylated by various serine/threonine kinases to regulate multiple cellular functions. We recently reported that the serine/threonine kinase TGF-β-activated kinase-1 (TAK1) is highly expressed and auto-phosphorylated to mediate critical growth and survival signaling in MM cells. We demonstrate here that regulation of PP2A activity inversely affects the phosphorylation levels of TAK1 in MM cells, and that MM cells aberrantly overexpress cancerous inhibitor of PP2A (CIP2A), an endogenous inhibitor for PP2A. CIP2A gene silencing as well as treatment with the CIP2A inhibitor TD52 potently induced MM cell death along with suppression of TAK1 expression in MM cells. These results suggest the critical role of PP2A inactivation via CIP2A upregulation in TAK1 phosphorylation and its protein expression and thereby MM cell growth and survival, posing the CIP2A-PP2A axis as an important therapeutic target.