TY - JOUR
T1 - Haploidentical transplantation in patients with multiple myeloma making use of natural killer cell alloreactive donors
AU - Van Elssen, Catharina
AU - van Gorkom, Gwendolyn
AU - Voorter, Christine
AU - von Dem Borne, Peter
AU - Meijer, Ellen
AU - Wieten, Lotte
AU - Bos, Gerard
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2021/1
Y1 - 2021/1
N2 - 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
AB - 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
KW - Stem cell transplantation
KW - Multiple myeloma
KW - NK cells
KW - NK CELLS
KW - HEMATOLOGIC MALIGNANCIES
KW - LIGAND MISMATCH
KW - BONE-MARROW
KW - KIR
KW - GRAFT
KW - SURVIVAL
KW - NKG2D
KW - HSCT
U2 - 10.1007/s00277-020-04303-z
DO - 10.1007/s00277-020-04303-z
M3 - Article
C2 - 33112968
SN - 0939-5555
VL - 100
SP - 181
EP - 187
JO - Annals of Hematology
JF - Annals of Hematology
IS - 1
ER -