Outcomes appear similar with MAC and RIC
SALT LAKE CITY—New research suggests outcomes may be similar whether patients receive myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) prior to haploidentical peripheral blood stem cell transplant (haploPBSCT) with post-transplant cyclophosphamide (PTCy).
Results from 2 parallel, phase 2 trials showed that MAC-PTCy-haploPBSCT and RIC-PTCy-haploPBSCT produced comparable rates of engraftment, acute and chronic graft-versus host disease (GVHD), relapse, and non-relapse mortality (NRM).
Rates of overall survival (OS) and event-free survival (EFS) were significantly higher in the MAC group. However, the fact that some RIC recipients had received prior allogeneic transplants—and none of the MAC recipients had—appeared to play a role in survival outcomes.
Junichi Sugita, MD, PhD, of Hokkaido University in Sapporo, Japan, presented these results at the 2018 BMT Tandem Meetings (abstract 50*).
To compare MAC and RIC in the context of PTCy-haploPBSCT, Dr Sugita and his colleagues conducted 2 parallel studies—JSCT Haplo 14 MAC and JSCT Haplo 14 RIC.
Patients
There were 50 patients in the MAC trial and 77 in the RIC trial. They had median ages of 36 (range, 17 to 60) and 58 (range, 22 to 65), respectively (P<0.01). There was a greater percentage of male patients among MAC recipients (82% vs 62%, P=0.028).
Diagnoses were similar between the groups and included:
- Acute myeloid leukemia—23 MAC, 34 RIC
- Acute lymphoblastic leukemia—11 MAC, 14 RIC
- Myelodysplastic syndromes/myeloproliferative neoplasms—6 MAC, 12 RIC
- Lymphoma—6 MAC, 14 RIC
- “Other”—4 MAC, 3 RIC.
Forty-eight percent (n=24) of MAC recipients and 58% (n=45) of RIC recipients were not in remission at transplant (P=0.48). There were no significant differences in disease risk index (P=0.34).
Thirty-nine percent of RIC recipients (n=30) had a history of allogeneic transplant, but none of the MAC recipients did (P<0.01).
Conditioning and prophylaxis
There were 2 MAC regimens. One consisted of fludarabine (Flu, 30 mg/m2/day on days -6 to -4) plus total body irradiation (TBI, 12 Gy on days -3 to -1). The other consisted of Flu (30 mg/m2/day on days -6 to -2), busulfan (BU, 3.2 mg/kg/day on days -6 to -3), and TBI (4 Gy on day -1).
The RIC regimen consisted of Flu (30 mg/m2/day on days -6 to -2), BU (3.2 mg/kg/day on days -4 to -3), and TBI (4 Gy on day -1).
All patients received GVHD prophylaxis consisting of cyclophosphamide (50 mg/kg/day on days 3 and 4), tacrolimus (days 5 to 180), and mycophenolate mofetil (days 5 to 60).
Graft
Siblings were the most common donors for MAC recipients (50%, n=25), followed by parents (28%, n=14), children (16%, n=8), and “other” donors (6%, n=3).
Children were the most common donors for RIC recipients (60%, n=46), followed by siblings (33%, n=25), and parents (8%, n=6).
There was no significant difference between MAC and RIC recipients when it came to human leukocyte antigen matching, cytomegalovirus serostatus, or CD34 cell dose.
However, there was a significant difference in donor-recipient gender matching (P=0.033).
Fifty-two percent (n=26) of MAC recipients and 62% (n=48) of RIC recipients had a donor-recipient gender match. Forty-two percent (n=21) and 22% (n=17), respectively, had female donor to male recipient.
Engraftment and GVHD
“Hematopoietic recovery was similar between MAC and RIC,” Dr Sugita said.
The cumulative incidence of neutrophil engraftment was 98% in MAC recipients and 94% in RIC recipients. The median time to neutrophil engraftment was 17 days and 18 days, respectively (P=0.10).
The cumulative incidence of platelet engraftment was 84% in the MAC recipients and 74% in the RIC recipients. The median time to platelet engraftment was 31 days and 37 days, respectively (P=0.32).
