In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e23551-e23551
Abstract:
e23551 Background: Patients with relapsed solid tumors have dismal predicted OS 〈 10-20% at 5 years with conventional salvage therapies. We hypothesized that a multi-faceted immunotherapy approach to optimize graft-versus-tumor (GVT) effects, in combination with a mammalian target of rapamycin (mTOR) inhibitor maintenance strategy, would enhance early disease-control rates (DCR), leading to improved progression-free survival (PFS) and OS for this high-risk population. Methods: Treatment consisted of HLA-haploidentical marrow (n = 12) or peripheral blood stem cell (n = 3) transplantation to optimize GVT effects, preceded by reduced-intensity conditioning (fludarabine, cyclophosphamide, and 3 Gy total body irradiation) to promote engraftment of these mismatched stem cells. Haplo-NK cells were given to boost this GVT effect. They were purified from non-mobilized donor mononuclear cells by CD3 depletion followed by CD56 selection using the Miltenyi CliniMACS system and were infused fresh on day +7 after HCT. Postgrafting immunosuppression included sirolimus maintenance, which continued until 6 months post-HCT. Results: Fifteen patients with relapsed Ewing sarcoma (EWS) (n = 9), rhabdomyosarcoma (n = 4), osteosarcoma (n = 1), and medulloblastoma (n = 1) having stable or undetectable gross disease were enrolled on this Phase II trial. Median age at HCT was 19 (4.5-37) years old and median performance status was 80%. Four patients underwent prior autologous transplants. Patients received a median NK dose of 6.5 (3.7-11.4) x 10 6 /kg. NK cell products had a median log T cell depletion of 5.94 (5.18-6.75), median NK recovery of 62% (48-71%), and median NK purity of 92% (74%-97%). All donor NK infusions were well-tolerated without cytokine release syndrome. All patients engrafted, and all had sustained full donor chimerism ( 〉 95% CD3). Two patients developed grade II acute graft-versus-host disease (GVHD), and 2 patients developed chronic GVHD. No patients died from transplant-related causes. With a median follow-up of 1.3 years (range, 70 days – 5 years), 6-month DCR is 72%. 1- and 2-year OS for the entire cohort is estimated at 64% and 40%, respectively, while PFS is 29% and 22%, respectively. For patients with EWS,1- and 2- year -OS is estimated at 75% and 45%, and PFS is 38% and 25%, respectively. Conclusions: This dual immunotherapy approach followed by mTOR inhibition maintenance was well-tolerated, with better than expected OS for this high-risk set of diseases. Clinical trial information: NCT02100891 .
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.e23551
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
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