The combination of a proteasome inhibitor, an IMiD and corticosteroid is known to be highly effective among patients with myeloma and is the rationale for this pilot study.

POEMS syndrome is a rare paraneoplastic syndrome caused by an underlying plasma cell disorder.  Information regarding treatment has mostly been gleaned from retrospective data. 

We designed a pilot study using a 28-day oral regimen of ixazomib-lenalidomide-dexamethasone.  Eligibility included a diagnosis of POEMS syndrome, plasma VEGF>200 pg/mL and performance status<3.  There were two groups (intended enrollment 15/group): Group A, 3 cycles for patients destined for high-dose chemotherapy with stem-cell transplant; Group B, 13 cycles for patients with relapsed or refractory disease. Primary endpoint was VEGF complete response (CR) after 3 cycles.  Secondary endpoints included safety, hematologic response, and overall survival at 3 and 12 months.  Other domains including neurologic response (Neuropathy Impairment Score (NIS), nerve conduction studies (NCS)) were also studied.  To date, 13 patients enrolled since 10/31/2016 – 4 to Group A and 9 to Group B. 

11 patients received the intended treatment while 2 dropped out before receiving therapy. Of those treated, median age was 55 years (range 39-77).  3 patients were female.  Eight (73%) met the primary endpoint.  Median follow-up was 16 months; 2 patients progressed after completing study and 1 progressed on therapy.   Baseline NIS score was 67.5 points (15-119.5).  Baseline NCS demonstrated median ulnar motor amplitude 6.1mV (0-13.6), ulnar sensory amplitude 13uV (0-36) and R1 blink latency 13.8ms (9.8-18.1).  3 month follow-up demonstrated median NIS 53.5 points (24-104.5), median ulnar motor amplitude 5.9mV (0.1-13.1), ulnar sensory amplitude 7.5uV (0-29) and R1 blink latency 12.55ms (10.6-17.7). 

This interim analysis suggests that ixazomib-lenalidomide-dexamethasone is an effective regimen for patients with POEMS syndrome.  3-month follow-up shows trend toward improvement in neuropathy impairments.  R1 blink latency may detect early improvement in NCS.