Ruben Mesa, MD, Director Mays Cancer Center, UT Health San Antonio, MD Anderson Cancer Center discusses The Future Directions in MPN: Novel Approaches and New Agents.
Ruxolitinib has been well-established as the standard of care for patients with moderate or high-risk myelofibrosis (MF), however, survival results are low for patients who discontinue ruxolitinib.1 While emerging data continue to support the role of JAK inhibitors in the treatment of MF, there is a need for novel agents and treatment strategies to broaden treatment options for these patients. "This paper summarizes key data from studies examining novel agents discussed during a recent MediCom Expert Roundtable," The Effect of New Myelofibrosis Data on the Changing Treatment Environment. "As noted in the following extracts, these recent findings were reviewed by Dr. Prithviraj Bose and Dr. Ruben Mesa and gave their expert perspective on the clinical importance of these results.
Ruxolitinib Combination Approaches with
In MF, ruxolitinib and thalidomide
In a multicenter, two-stage, phase 2 trial, the combination of ruxolitinib and thalidomide was investigated to see if this strategy could improve disease-related cytopenias and therapy-related cytopenias, as well as improve overall disease response in patients with MF.2 The trial included patients with either primary or secondary MF and those receiving ruxolitinib therapy at e-treatment. Patients must have been on ruxolitinib for at least 3 months and must have been on a steady dose for at least 4 weeks prior to enrollment. Treatment-naïve patients received single-agent ruxolitinib for 3 months during the run-in process and proceeded to receive combination therapy if less than PR was reached. Each therapy duration was 28 days long. The primary endpoint was the percentage of subjects treated that obtained a response based on IWG-MRT and platelet response parameters.
The findings showed a significant increase in platelet count at the third cycle of combination therapy versus baseline (P < .01) and a significant increase in platelet count in patients with baseline thrombocytopenia at the same time point (P < .05). At the time of reporting, 15 of the 23 patients enrolled were evaluable. Over successive cycles of combination therapy, investigators have observed a trend towards a rise in hemoglobin. 6 out of 11 patients (56 percent) with available CT / MRI data had a decrease in spleen volume after at least 3 cycles of combination therapy. In 7 of 15 patients (46.6 percent), the overall response rate (ORR) was 60 percent and clinical progress (i.e. anemia response, symptom response, or spleen response) was registered. Six (75 percent) of the 8 patients with baseline thrombocytopenia had a platelet response.
What is the clinical significance of such results?
Ruxolitinib Plus Pomalidomide in MF Anemia Patients: Findings Updated from the German MPNSG-0212 Trial
In an ongoing, multi-center, open-label, single-arm, phase 1b/2 trial, the combination of ruxolitinib and pomalidomide is being investigated.3 The objective of the study is to assess the possible synergism of ruxolitinib + pomalidomide in patients with MF to improve anemia and quality of life ( QoL). The study was planned to include a two-stage target population of 90 patients: patients in Cohort 1 received ruxolitinib 10 mg BID plus low-dose pomalidomide 0.5 mg QD and patients in Cohort 2 received step-by-step pomalidomide dose increases from 0.5 mg to 1 mg and 2 mg QD after three and six 28-day periods, respectively. MF with anemia (Hb < 10 g / dL and/or RBC transfusion dependency [RBC-TD]) was the major inclusion criterion. The study removed patients and those with low platelet counts (< 100 / nL) who were eligible for allogeneic transplantation.
Sixty-seven of the 79 patients included in the data cut-off were evaluable (Cohort 1, n=40; Cohort 2, n=27).3 The efficacy findings showed that 18% and 20% of patients in Cohorts 1 and 2, respectively, achieved clinical improvement [Hb increase ⁇ 2 g / dL]. Notably, 42% of all patients underwent > 12 cycles and demonstrated a longer-lasting stabilization of their disease with continuous improvement of Hb and QoL.