2018 BMT Tandem Meetings
SALT LAKE CITY—An expanded umbilical cord blood (UCB) product can produce favorable outcomes as a stand-alone graft, according to a presentation at the 2018 BMT Tandem Meetings.
The product, MGTA-456, provided “rapid and durable” engraftment in patients with hematologic malignancies, according to John E. Wagner, MD, of the University of Minnesota in Minneapolis.
He also said MGTA-456 “preserved the clinical benefits” of UCB transplant, including low rates of graft-vs-host disease (GVHD) and high overall survival (OS).
Dr Wagner presented these results as one of the “Best Abstracts” at this year’s BMT Tandem Meetings (abstract 4). The research was supported by Novartis and Magenta Therapeutics.
MGTA-456 is developed by dividing a UCB unit into a CD34- portion and a CD34+ portion, then expanding the CD34+ portion for 15 days via culture with an aryl hydrocarbon receptor antagonist (SR-1), stem cell factor, FLT3 ligand, interleukin-6, and thrombopoietin.
In a previous study,* MGTA-456 enhanced hematopoietic recovery when given as half of a double UCB transplant.
With the current research, Dr Wagner and his colleagues evaluated MGTA-456 as a stand-alone graft. The team conducted two phase 2 trials of MGTA-456, one in which patients received myeloablative conditioning (MAC) and one in which patients received non-myeloablative conditioning (NMAC).
Treatment
Each trial included 10 patients with a high-risk hematologic malignancy and a partially HLA-matched UCB unit. In each trial, 1 patient could not receive MGTA-456 due to low expansion.
So 9 patients received MAC—cyclophosphamide (CY) at 60 mg/kg/day on days -6 and -5, fludarabine (FLU) at 25 mg/m2/day on days -7 to -5, and total body irradiation (TBI) at 1320 cGy on days -4 to -1.
And 9 patients received NMAC—CY at 50 mg/kg on day -6, FLU at 40 mg/m2/day on days -6 to -2, and TBI at 200 cGy on day -1. Some patients who had not received recent chemotherapy also received antithymocyte globulin as part of their conditioning regimen.
For MAC recipients, the median expansion of CD34+ cells was 406-fold (range, 162-1643). The median CD34 cell dose they received was 16.2 x 106/kg.
For NMAC recipients, the median expansion of CD34+ cells was 274-fold (range, 42-527). The median CD34 cell dose they received was 13.4 x 106/kg.
All patients received cyclosporine and mycophenolate mofetil as GVHD prophylaxis.
Dr Wagner and his colleagues compared outcomes in these MGTA-456 recipients to outcomes in historical control subjects—151 patients who received MAC and 132 who received NMAC.
MAC recipients
The 9 MAC/MGTA-456 recipients had a median age of 25 (range, 15-53). Seven of the patients had acute leukemia, 1 had myelodysplastic syndrome (MDS), and 1 had lymphoma.
Eleven percent of patients had high-risk disease, 89% were cytomegalovirus seropositive, and 89% had a Karnofsky performance score of 90 to 100.
The only significant difference between the MGTA-456 recipients and historical controls was weight. The median weight was 93.8 kg (range, 41-107) for MGTA-456 recipients and 66.7 kg (range, 11-136) for controls (P=0.04).
The MGTA-456 recipients had superior hematopoietic recovery compared to historical controls.
The rate of neutrophil engraftment was 100% for MGTA-456 recipients and 89% for controls. The median time to neutrophil engraftment was 14 days and 23 days, respectively (P<0.01).
The rate of platelet engraftment was 89% for MGTA-456 recipients and 71% for controls. The median time to platelet engraftment was 46 days and 64 days, respectively (P=0.01).
There was no significant difference between MGTA-456 recipients and historical controls when it came to GVHD or OS.
The incidence of grade 3-4 acute GVHD at 100 days was 22% for MGTA-456 recipients and 24% for controls (P=0.78). The incidence of chronic GVHD at 1 year was 11% and 21%, respectively (P=0.48).
The 2-year OS rate was 67% in MGTA-456 recipients and 55% in controls (P=0.59).
NMAC recipients
There were significant differences between the 9 NMAC/MGTA-456 recipients and the 132 NMAC historical controls when it came to age (P=0.03), disease type (P<0.01), and disease status (P=0.03).
The median age was 65 (range, 29-70) for MGTA-456 recipients and 53 (range, 6-72) for historical controls. The median weights were 93.4 kg (range, 55-111) and 81.4 kg (range, 22-145), respectively.
Diagnoses among MGTA-456 recipients included acute leukemia (n=1), MDS (n=4), chronic leukemia (n=1), lymphoma (n=1), and “other” (n=2). Diagnoses among historical controls included acute leukemia (n=61), MDS (n=25), chronic leukemia (n=9), lymphoma (n=35), and “other” (n=2).
Eighty-nine percent of MGTA-456 recipients and 49% of historical controls had high-risk disease. Sixty-seven percent and 64%, respectively, were cytomegalovirus seropositive. Sixty-seven percent and 85%, respectively, had a Karnofsky performance score of 90 to 100.
NMAC recipients who received MGTA-456 had superior neutrophil recovery but platelet recovery that was comparable to that of historical controls.
The rate of neutrophil engraftment was 100% in MGTA-456 recipients and 95% in historical controls. The median time to neutrophil engraftment was 7 days and 15 days, respectively (P<0.01).
The rate of platelet engraftment was 56% for MGTA-456 recipients and 77% for historical controls. The median time to platelet engraftment was 107 days and 47 days, respectively (P=0.19).
There was no significant difference between MGTA-456 recipients and historical controls when it came to GVHD or OS.
The incidence of grade 3-4 acute GVHD at 100 days was 43% for MGTA-456 recipients and 15% for controls (P=0.11). The incidence of chronic GVHD at 1 year was 0% and 19%, respectively (P=0.17).
The 2-year OS rate was 44% in MGTA-456 recipients and 49% in controls (P=0.80).
*Wagner JE Jr et al; Phase I/II Trial of StemRegenin-1 Expanded Umbilical Cord Blood Hematopoietic Stem Cells Supports Testing as a Stand-Alone Graft. Cell Stem Cell 2016; 18(1):144-155.