A Final Analysis of a Phase 2, Single-Arm Study of Platelet (Plt) Responses and Remission Rates in Patients with Immune Thrombocytopenia (ITP) Receiving Romiplostim

Background: We describe here plt response and remission observed with romiplostim in patients with ITP for ≤6 months (mos).

Methods: Patients with ITP for ≤6 mos who received 1^st-line therapies only subsequently received 12 mos of weekly (QW) romiplostim (Fig 1). The 1º objective was the # of mos with a plt response during the 12 mos; 2º objectives included incidence of remission and splenectomy. The romiplostim dose was increased QW by 1 μg/kg from 1 μg/kg to 10 μg/kg, adjusting to maintain a plt count of 50-200x10⁹/L. Patients with plt counts ≥50x10⁹/L on romiplostim only at the end of 12 mos entered a dose-tapering period in which the dose was decreased by 1 μg/kg Q2W as long as plt counts were ≥50x10⁹/L. When the dose decreased to 0 during either the 12 mos or the dose taper, patients were evaluated for remission (24 wks plt counts ≥50x10⁹/L with no ITP treatments, including romiplostim). Patients who at the end of 12 mos 1) had plt counts ≤20x10⁹/L for <4 consecutive wks, 2) had plt counts of 20-50x10⁹/L, 3) were receiving ITP treatment besides romiplostim, and/or 4) did not show onset of remission in the taper period could enter a stabilization period (≤8 wks) while the investigator determined suitable post-study therapy. Patients with plt counts ≤20x10⁹/L for ≥4 consecutive wks on the maximum dose (10 μg/kg) were discontinued from the study for non-response.

Results: Of the patient population (N = 75), 59% were women, median (Q1, Q3) age was 39 (29, 57) years, median (Q1, Q3) time since ITP diagnosis was 2.2 (0.9, 4.3) mos, and median (Q1, Q3) screening plt count was 20 (12, 25)x10⁹/L. Past treatments included steroids (96%), IVIG (44%), and anti-D (1%); prior to the study, 8% of patients received plt transfusions. 59 patients (79%) completed treatment, 16 (21%) discontinued romiplostim [consent withdrawn n = 4, alternative therapy 4, adverse event (AE) 3, lost to follow-up 2, protocol deviation 1, death 1, splenectomy 1]. Patients had a median (Q1, Q3) of 51 (18, 52) wks of treatment during the 12-mo treatment period with a median (Q1, Q3) average QW dose of 2.6 (1.6, 3.9) μg/kg; 70 of 75 patients (93%) had a peak plt count ≥50x10⁹/L. The median (Q1, Q3) # of mos out of the 12-mo period with a plt response was 11 (8, 12); the median (95% CI) time to first plt response was 2.1 (1.1, 3.0) wks (Table, also plt counts in Fig 2). ITP remission occurred in 24 patients (32%, 95% CI: 22%, 44%) with a median (range) time to onset of 27 (6-57) wks. 7 patients had treatment failure (plt count ≤20x10⁹/L for 4 consecutive wks at 10 μg/kg QW, alternative therapy, or death), including 1 with a splenectomy. The most common AEs were headache (16%), arthralgia (15%), and nasopharyngitis (12%). The most common hemorrhage AEs were hematoma (11%), petechiae (8%), and epistaxis (7%). 14 patients had serious adverse events (SAEs); 3 were treatment-related (gastritis, increased transaminases, and reversible ischemic neurological deficit). Other SAEs, occurring in 1 patient each, except thrombocytopenia (n = 2), included acute renal failure, atrial fibrillation, dapsone syndrome, delirium tremens, erysipelas, fecaloma, non-Hodgkin's lymphoma (NHL), papillary thyroid cancer, pleuritic pain, and tendon rupture. There were 4 AEs leading to romiplostim discontinuation (delirium tremens, NHL, leukocytosis, and increased transaminases, only this last being treatment-related). There were no fatalities reported as AEs; the death leading to discontinuation was due to cerebral hemorrhage which began before the patient received romiplostim. Neutralizing antibodies to romiplostim were found in 1 patient at routine testing at the end of study; this patient had a plt response for 11 of 12 mos but did not enter remission.

Conclusions: In this trial, patients with an ITP diagnosis for ≤6 mos treated with romiplostim had a high response rate (over 90%), with plt responses occurring quickly (median time to first response of 2 wks). The median # of mos out of the 12-mo period with a plt response was 11. Remission occurred in 32% of patients; splenectomy occurred in 1 patient only. In conclusion, in this study, remission was observed in ~1/3 of adult patients with ITP for ≤6 mos who were treated with romiplostim.

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