PS1467 EARLY RESULTS OF A PHASE II STUDY OF COMBINED RUXOLITINIB AND THALIDOMIDE IN PATIENTS WITH MYELOFIBROSIS
Authors: R. Rampal, S. Verstovsek, S. Devlin, E. Stein, T. Kadia, M. Mauro, P. Naveen, G. Montalban‐Bravo, A. King, K. Alvarez, N. Ard, T. Goodman, B. Taylor, P. Bose
Journal: HemaSphere (2019)

Background: Among the most frequent and challenging hematologic manifestations of myelofibrosis (MF) are anemia and thrombocytopenia, the presence of which portends an adverse outcome. Few effective modalities to address these cytopenias exist, particularly thrombocytopenia. Further, although Ruxolitinib (RUX) has demonstrated significant clinical efficacy in MF patients, RUX frequently results in anemia and thrombocytopenia. Thalidomide (THAL) is an immunomodulatory agent which has demonstrated demonstrated improvements in anemia and thrombocytopenia in patients with MF. Aims: We sought to examine whether the combination of RUX and THAL could result in improvement in both disease‐ and therapy‐related cytopenias, as well as improve overall disease response in patients with MF. Methods: We conducted a multicenter two stage phase II trial designed to assess the effect of RUX and THAL combination in subjects with myelofibrosis (NCT03069326). Patients taking RUX at the time of enrollment must have had less than PR per IWG‐MRT/ELN 2013 criteria. Patients must have been taking RUX for a minimum of 3 months. Treatment‐naïve patients received single‐agent RUX for 3 months (run‐in phase) per label, and went on to combination therapy if they achieved less then a PR. Each cycle of therapy was 28 days. Response assessment was evaluated according to the IWG‐MRT/ELN 2013 criteria. Platelet response criteria (in patients with baseline thrombocytopenia) included: Major response (≥75% increase in platelet count), Intermediate Response (50–74% increase) and Minor Response (25–49% increase). Adverse events were assessed using the NCI CTCAE v. 4.0. The primary endpoint was the proportion of treated subjects that achieved a response by IWG‐MRT criteria and by platelet response criteria. Results: A total of 25 patients are planned to be accrued. At the time of this writing, 24 have been accrued. The median age was 70 years (43–85). 9 patients had received prior therapies. 11 patients enrolled to the run‐in phase. 16 patients had received red blood cell transfusions prior to study enrollment. A significant increase in platelet count was observed by cycle 3 of therapy compared to baseline (Figure 1A, P &lt; 0.05). An increase in Hgb was observed over successive cycles of combination therapy (Figure 1B). 12 of 21 accrued patients were evaluable for response assessment at the time of abstract submission. The overall response rate in these patients was 58.3% (7/12 patients). Four of 12 (33.3%) evaluable patients had stable disease. 1 patient progressed to accelerated phase. Clinical Improvement (anemia response, spleen response, or symptom response) occurred in 5 patients. Major platelet response was observed in 6 patients with baseline thrombocytopenia (Table 1). Grade 3/4 non‐hematologic adverse events regardless of attribution included; limb edema, diverticulitis, hypertension, syncope, and a thromboembolic event (one patient each). Summary/Conclusion: The combination of THAL and RUX has demonstrated a promising efficacy signal in this initial analysis of an ongoing phase II study, and appears to be well tolerated. Reductions in spleen size, symptom burden, and improvements in hemoglobin and platelet count were observed. Improvement in platelet count is particularly important given the lack of treatment modalities for thrombocytopenia in this patient population. These data indicate a potential role for this regimen in patients with cytopenias and/or persistent disease manifestations while on RUX. Updated data on duration of response and overall response rate in all accrued patients will be presented. image