634. Myeloproliferative Syndromes: Clinical: JAK Inhibitors and Combination Therapies

Conclusion cited from the abstract: PAC 200 mg BID is generally well tolerated and has demonstrated clinical activity, particularly in patients with severe thrombocytopenia (platelet count <50,000/mL). The PAC203 population is characterized by high-risk, advanced, and heavily pre-treated disease; even in this group, PAC 200 mg BID was associated with reduction in spleen size and symptom burden using stringent, front-line response criteria (SVR ≥35% and TSS ≥50%). An upcoming phase 3 study (PACIFICA), including patients with MF and severe thrombocytopenia that are either naïve to or have had a limited duration of prior JAK2 inhibitor therapy, will compare PAC 200 mg BID vs. physician’s choice.




Conclusion cited from the abstract: 

Combination treatment using RUX plus POM is feasible in pts with poor-risk MF and resulted in an objective anemia response rate of 18% in co1. Of note, 42% of pts were treated with >12 cycles and showed a longer lasting stabilization of their disease with sustained improvement of Hb and QoL. Step-wise increase of the POM dose in co2 is safe and feasible with 70% of pts still on study treatment. Updated efficacy results of co2 with longer follow-up data will be presented at the meeting.





Conclusion cited from the abstract: Early results of this pilot study indicate that Rux administration at 10 mg BID in MF patients undergoing HCT is safe and feasible, with 100% engraftment and low rate of acute GVHD. We are currently accruing an expansion cohort of 6 patients at DL2. Results of our PK studies indicated a direct correlation between Cmax and AUC and that higher oral clearance compared to previous study is most likely due to poor GI absorption of the drug in HCT patients. More follow up is needed to see the impact of this combination on incidence of chronic GVHD. This regimen may also be useful for patients undergoing HCT for other hematologic malignancies.




Conclusion cited from the abstract: Preliminary data indicate that CPI-0610 alone or “add-on” to rux is generally well-tolerated and provides clinical benefits in MF pts with inadequate responses or who are refractory to rux. Improvement in BM fibrosis and anemia responses indicate the potential for meaningful disease modification. Based on the available data, Arm 2 TD cohort has achieved proof-of-concept for TI. Further expansion of the MANIFEST study is ongoing. Updated data will be presented.




Jacqueline S Garcia, et al. 

Conclusion cited from the abstract: Navitoclax in combination with ruxolitinib was well tolerated with clinically meaningful spleen responses, allelic burden reductions, TSS improvements, and encouraging improvements in BMF in pts with MF who have received prior Tx with ruxolitinib. 


Conclusion cited from the abstract: Pts with MF who entered JAKARTA or JAKARTA2 with PLT counts <100 × 109/L achieved similar spleen volume and symptom RRs with FEDR, whether used as first-line therapy, as pts with BL PLT counts ≥100 × 109/L. FEDR was generally well tolerated in pts with very low PLT counts at BL. FEDR is a promising new Tx option for pts with MF and low PLT counts who might otherwise receive suboptimal Tx.