Decitabine, Vorinostat, and Haploidentical Natural Killer Cell Infusions with IL-2 Stimulation in High-Risk Myelodysplastic Syndrome.

Myelodysplastic Syndromes (MDS) describe a heterogeneous group of hematologic malignancies with variable prognoses and allogeneic hematopoietic stem cell transplantation the only known potential cure. Standard therapy with Hypomethylating Agents (HMA) change the natural history of the disease; however, response duration is limited. Additional treatments are needed.Between 2013 and 2015, we enrolled high-risk MDS patients on a clinical trial utilizing a combination of decitabine, vorinostat, and haploidentical related Natural Killer (NK) cells followed by IL-2 stimulation. Patients received 2 cycles utilizing a fresh NK cell product with cycle 1 and a cryopreserved NK cell product with cycle 2. Nine patients were treated on this study conducted at the University of Minnesota and the Mayo Clinic in Rochester.

We observed an overall response rate of 56% (5 of 9) including Marrow Complete Remission (mCR) (n=3), partial cytogenetic response (n=2), stable disease (SD) (n=3), and progressive disease (PD) (n=1). Toxicity was minimal. The majority of grade 3 events were infectious (36%) or gastrointestinal (25%) and grade 4 events were limited to cytopenias. Donor NK cell expansion was not observed but endogenous NK cell killing was increased and was present after both cycle 1 and cycle 2.Our older high-risk MDS population tolerated sequential decitabine, vorinostat, and haploidentical NK cell infusions with IL-2 administration and experienced good response rates. Unlike previous studies using more potent lymphodepletion, we did not observe donor NK cell expansion with this outpatient regimen and thus further study with a more intensified immunosuppressive platform is warranted.