Phase II Trial of Haploidentical Hematopoietic Cell Transplantation (HCT), Natural Killer (NK) Cell Infusion, and Sirolimus Leads to Long-Term Survival in Select Patients with High-Risk Solid Tumors — ASN Events
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  2. Poster Session Two
  3. Phase II Trial of Haploidentical Hematopoietic Cell Transplantation (HCT), Natural Killer (NK) Cell Infusion, and Sirolimus Leads to Long-Term Survival in Select Patients with High-Risk Solid Tumors

Phase II Trial of Haploidentical Hematopoietic Cell Transplantation (HCT), Natural Killer (NK) Cell Infusion, and Sirolimus Leads to Long-Term Survival in Select Patients with High-Risk Solid Tumors (#237)

Nathan Schloemer 1 , John Charlson 1 , Meghen Browning 1 , David Margolis 1 , Parameswaran Hari 1 , Brent Logan 1 , Michael Kelly 2 , Amy Newman 1 3 , Bryon Johnson 1 , Carolyn A. Keever-Taylor 1 , Subramaniam Malarkannan 4 , Monica S. Thakar 5
  1. Medical College of Wisconsin, Milwaukee, WI, United States
  2. Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, United States
  3. Marquette University College of Nursing, Milwaukee, WI, United States
  4. Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, United States
  5. Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States

Background: Patients with relapsed/refractory solid tumors have dismal overall survival (OS) with conventional therapies. We hypothesized that a multifaceted immunotherapy approach using allogeneic HCT with prophylactic NK cell infusion plus mammalian target of rapamycin (mTOR) inhibitor maintenance strategy, could enhance early disease-control rates (DCR), leading to improved OS.

Methods: Patients underwent reduced-intensity conditioning (fludarabine/cyclophosphamide/3 Gy total body irradiation) to promote engraftment followed by HLA-haploidentical marrow (n=12) or peripheral blood stem cells (n=3). Donor mononuclear cells underwent CD3 depletion/CD56 selection (Miltenyi CliniMACS) to obtain NK cells, which were infused fresh on day +7 post-HCT. Post-grafting immunosuppression included post-HCT cyclophosphamide and sirolimus maintenance (day +20-+180). DCR was defined as complete response + partial response + stable disease. OS was calculated by Kaplan-Meier method. Non-relapse mortality (NRM) was defined as death not preceded by relapse/progression.

Results: Fifteen heavily pretreated patients (prior autologous HCT, n=4) with relapsed/refractory Ewing sarcoma (EWS; n=9), rhabdomyosarcoma (RMS; n=4), osteosarcoma (n=1), and medulloblastoma (n=1) having stable/undetectable gross disease at time of HCT were enrolled. Median age at haploidentical HCT was 17 (4-36) years. Patients received a median NK dose of 6.5 (3.7-11.4) x 106/kg with median log T-cell depletion of 5.94 (5.18-6.75). No infusional toxicities/cytokine release syndrome occurred. All patients engrafted with sustained full donor chimerism. Two patients developed grade II acute graft-versus-host disease (GVHD), and 3 developed chronic GVHD. DCR at 6 months was 67%. There were no cases of NRM. 1- and 2-year OS for the entire cohort was estimated at 67% and 47%, respectively. For patients with EWS,1- and 2-year OS was estimated at 78% and 56%, respectively. Notably, there are 4 long-term survivors (EWS=3, RMS=1) 7.8-10 years post-HCT.

Conclusions: Haploidentical HCT with donor NK immunotherapy followed by mTOR inhibition maintenance therapy was well-tolerated. In select patients, there was adequate disease control to allow long-term survival.