1. Haploidentical transplantation in patients with multiple myeloma making use of natural killer cell alloreactive donors.
- Author
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Van Elssen C, van Gorkom G, Voorter C, von dem Borne P, Meijer E, Wieten L, and Bos G
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Multiple Myeloma diagnosis, Multiple Myeloma mortality, Prospective Studies, Survival Rate trends, Transplantation, Homologous methods, Killer Cells, Natural transplantation, Living Donors, Multiple Myeloma therapy, Transplantation, Haploidentical methods
- Abstract
Disease relapse is an important problem after allogeneic stem cell transplantations in multiple myeloma (MM). To test the hypothesis that natural killer (NK) cell alloreactivity in the setting of a haploidentical stem cell transplantation (haploSCT) can reduce the risk of myeloma relapse, we performed a small prospective phase 2 study in which we transplanted poor-risk MM patients using a killer cell immunoglobulin-like receptor (KIR)-ligand mismatched haploidentical donor. Patients received bone marrow grafts after reduced-intensity conditioning, with post-transplantation cyclophosphamide (PTCY) graft-versus-host-disease (GVHD) prophylaxis. The primary endpoint was 1.5-year progression-free survival (PFS); stopping rules were installed in case interim results made a benefit of 50% PFS at 1.5 years unlikely. After inclusion of 12 patients, of which 9 were evaluable for the primary endpoint, all patients relapsed within a median time of 90 days. All except 1 patient showed engraftment, with a median time to neutrophil recovery of 18 (12-30) days. The study was prematurely terminated based on the predefined stopping rules after the inclusion of 12 patients. With this small study, we show that in chemo-resistant myeloma patients, NK cell KIR-mismatch is not superior to conventional alloSCT. This strategy, however, can serve as a platform for new treatment concepts.Clinical Trial Registry: NCT02519114.
- Published
- 2021
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