Histomorphological Responses after Therapy with Pegylated Interferon Alpha-2a in Patients with Essential Thrombocythemia (ET) and Polycythemia Vera (PV)

Introduction: We previously reported the long-term efficacy and safety of pegylated interferon alpha-2a (PEG-IFN-a-2a) in 83 patients with ET and PV after a median follow-up of 83 months. Here, we present the bone marrow (BM) response assessment according to modified International Working Group for-Myeloproliferative Neoplasms Research and Treatment (IWG-MPN). Objective: To identify histomorphological BM responses in patients with ET and PV treated with PEG-IFN-a-2a as part of a prospective phase II study. Methods: All patients had BM assessment done prior to their enrollment, and then every 6-12 months while on study if possible, and in some patients after treatment discontinuation. Complete BM remission (BM-CR) required absence of > grade 1 reticulin fibrosis and disappearance of megakaryocyte hyperplasia in ET or trilinear hyperplasia with age-adjusted normocellularity in PV. An incomplete, partial response (BM-PR), was defined when fibrosis grading had consistently improved by at least one grade level on at least 2 consecutive samples > 12 months apart, yet with persistent MPN morphological features. Hematologic (HR) and molecular response (MR) assessments were previously reported (ASH 2015, abstract #60). Results: Among 83 enrolled patients (43 PV, 40 ET), 58 patients (70%) had evaluable BM samples for histomorphological response assessment, with median number of 8 samples per patient (range, 3-12). Among the remaining 25 patients, 18 were treated ≤12 months, and 7 did not have representative samples. Median age was 52 years (range, 19-75), and 29% (n=17) were males. Median disease duration prior to enrollment was 31 months (range, 1-350), and the median exposure to PEG-IFN-a-2a was 80 months (range, 15-107). After a median follow-up of 84 months (range, 36-107), 32 patients are on study. Forty-two patients were JAK2 positive, 6 CALR positive, 2 MPL positive and 8 triple negative (TN). Hematologic and molecular (JAK2V617F mutation only) responses were seen in 54 (93%) and 29 (69% of JAK2V617F positive) patients, including complete HR and complete MR in 52 (90%) and 9 (31%) patients, respectively. In total, 29 evaluable patients (50%) had BM response, including 13 patients (22%) with BM-CR (MF-0 in 11, example in Figure 1). Among 16 patients with BM-PR, 3 had resolution of dense collagen bundles as well as decreased reticulin fibrosis. Except for increased platelets in those with BM-PR (p Conclusions: Histomorphological BM responses (including complete response) can occur in ET/PV patients treated with PEG-IFN-a-2a, and generally correlate with more durable treatment benefit. Complete BM responses may be sustained even after treatment discontinuation, or be seen after therapy discontinuation. Despite this, we could not identify a uniform correlation between hematologic, histomorphological and molecular response. Table Patients with BM assessment stratified by response, N=58 Table. Patients with BM assessment stratified by response, N=58 Figure BM assessment of a PV patient with BM-CR. A & C: Before treatment: increased cellularity and abnormal megakaryocytes number/morphology; MF-2. B & D: After treatment: normocellular BM, normal morphology, MF-0. Figure. BM assessment of a PV patient with BM-CR. A & C: Before treatment: increased cellularity and abnormal megakaryocytes number/morphology; MF-2. B & D: After treatment: normocellular BM, normal morphology, MF-0. Disclosures Cortes: ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding.