Background: Thalidomide, and its analog, lenalidomide have shown activity in WM, when combined with rituximab. However, neuropathy and anemia respectively, have limited their use. P is a newer generation IMID® which has demonstrated efficacy and tolerability in R/R multiple myeloma. These results provided the rationale for a phase I study of P in pts with R/R WM. Methods: Eligible pts had WM that was R/R to ≥ 1 prior therapy. All pts received daily oral P (28d cycles), starting at a 1mg dose level. Following a 3+3 statistical design, the dose was increased by 1 mg increments until the MTD was reached. Overall response was assessed as per International WM Working Group Response Criteria. Results: Between 10/2010-01/2014, 9 pts (7 males, 2 females) were treated. Median age at enrollment was 64 yrs (range 51-85), median time from 1^st therapy was 6.1 yrs (range 2.0-16.3), and median prior therapies was 2 (range 1-5). With a median f/u of 30 mos. (range: 6-36), 8 pts remain alive, and 1 continues to receive therapy. At 1 mg, no DLTs were seen, and pts received a median of 6 cycles (range: 4-12+). At 2 mg, 2 pts experienced DLTs, including dizziness (Gr 4) and syncope (Gr 3) in 1 pt and grade 4 neutropenia in 1 pt. A 3^rdpt withdrew after experiencing mild fever, headaches and blurred vision starting on day 4 of cycle 1. Fever and headache resolved with stopping P; blurred vision resolved after plasma exchange. Other grade 3-4 adverse events (AEs) included neutropenia (3 pts) and infection (knee joint, 1 pt). Gr 1-2 AEs include fatigue (6), rash (5), diarrhea (4), nausea/emesis (4), edema (3), myalgias (3), blurred vision (2), peripheral neuropathy (2), dyspnea (2), constipation (2), headache (2), dizziness (2), mucositis (1), infection [otitis media (1);URI –(3)], rash(1), pruritus (1), and night sweats (1). Among 8 evaluable pts, 2 had minor responses, 3 had stable disease (SD), and 3 had progressive disease as best response. Conclusions: The MTD of single agent P is 1 mg/day in pts with R/R WM. P provided ≥ SD in 63% of pts, suggesting that combinations with other effective agents should be studied. Abbreviated dosing schedules, such as d1-21 q28d may permit recovery of cytopenias between cycles, facilitating such combinations. Clinical trial information: NCT01198067.