Pilot trial of K562/GM-CSF whole-cell vaccination in MDS patients

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies. Currently, approved drugs are given with non-curative intent as the only known cure is allogeneic bone marrow transplantation, which relies on the donor’s immune system driving an allogeneic effect. Previous efforts to harness the endogenous immune system have been less successful. We present the results of a pilot study of K562/GM-CSF (GVAX) whole-cell vaccination in MDS patients. The primary objective of safety was met as there were no serious adverse events. One patient had a decrease in transfusion requirements and another demonstrated hematologic improvement suggesting a signal for clinical activity. In vitro correlative studies indicated biological effects on immune cells following vaccination. Although only a pilot study, results are encouraging that an immunotherapeutic approach with a whole-cell vaccine may be feasible in MDS patients.

Keywords:

• Cancer vaccine
• immunotherapy
• myelodysplastic syndrome
• phase 1 clinical trial

Acknowledgements

We kindly thank the research support staff at SKCCC and the patients who enrolled in the study. We also thank Dr. Hao Zhang at the Johns Hopkins School of Public Health Flow Cytometry Core Facility for assistance with cell sorting and Dr. Ian Kaplan at Adaptive Biotechnologies for assistance with TCRseq analysis. Experiments done though the human immunology core facility were supported by National Institutes of Health Grant [P30 CA006973].

Ethical approval

Informed consent was obtained from all individual participants included in the study.

Trial registration

This clinical trial predated the requirement for registration with ClinicalTrials.gov.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2018.1443449.