Yishai Ofran, MD, Director of Hematology department and Shaare Zedek Medical Center Jerusalem speaks about the ASH 2021 Abstract – 413 Allogeneic Transplantation in Fit Older Adults Is Feasible and Encouragingly Efficacious. Post Remission Data from the Prospective ECOG-ACRIN (E2906) Clinical Study.
Link to Abstract:
https://ash.confex.com/ash/2021/webprogram/Paper149356.html
Introduction:
The most effective anti-leukemia treatment after remission is allogeneic stem cell transplantation (alloSCT). However, the accompanying toxicity is a deterrent to its widespread use as standard of care in the elderly. Because randomized controlled trials comparing transplantation to non-transplantation are difficult to conduct, most studies of AML patients who had alloSCT are retrospective. The results of E2906, a randomized controlled phase III study that compared two intense chemotherapy arms, are presented here. At the option of the investigators, patients who achieved remission and had a donor were to undergo alloSCT after induction or first consolidation. Non-transplanted patients were given two consolidation cycles before being randomly assigned to observation or decitabine maintenance. All patients that got alloSCT on protocol during first remission (CR1) or at other post-induction time-points are documented here.
Patients and Procedures:
727 AML patients aged 60 and up were enrolled in the E2906 research. AlloSCT was conducted on 166 individuals, with 71 of them receiving it as part of the trial and 95 receiving it outside of it. AlloSCT was performed on 105 individuals (66/71 on protocol, 39/95 off protocol) at CR1/CRi1/LFS1 (CR: 92, CRi: 9 LFS: 4). Patients were monitored for a median of 33.6 months from diagnosis to transplant and 29.1 months thereafter. Prior to alloSCT, no patients got decitabine maintenance.
The time from allo transplant to death from any cause is defined as overall survival (OS), with follow-up censored at the date of last contact. The time from alloSCT transplant to relapse or death from any cause is referred to as disease free survival (DFS). For patients with no relapse or death information, the censored follow-up time is the date of last contact. OS and DFS were calculated using Kaplan-Meier estimations. Log rank tests were used to compare DFS and OS amongst subgroups. To assess the subgroup effect on time to relapse following transplant, a cumulative incidence analysis was performed using death without preceding relapse as competing events.
Results:
Patients who received alloSCT at CR1/CRi1/LFS1 have patient characteristics that are similar to the general population of AML patients eligible for intense treatment. The median age was 66 years, with 52 percent of the participants being male and 88 percent having an ECOG PS of 0-1. There were 85 patients with cytogenetic data, and 26 percent of them had unfavorable cytogenetics. Prior to alloSCT, 44 patients had their minimal residual disease (MRD) status determined, and 19 (43%) of them were MRD negative.
All 105 patients who received alloSCT at CR1/CRi1/LFS1 had long-term OS and DFS rates that were encouraging (Figure 1). At two years, OS and DFS were 56.4 percent and 53.6 percent, respectively, and at three and four years, 45.6 percent and 42.9 percent, 39 percent. Age, gender, induction regimen (3+7 or clofarabine), and MRD status prior to transplantation had no bearing on the outcome. The survival curves for people with intermediate or unfavourable cytogenetic risk aren’t very different. Patients with CRi1 or LFS1 have insufficient numbers to be compared to those with CR1. Nonetheless, 36 of the 38 patients who were alive and in the first remission at the time of the data cutoff attained CR1, although only 2/38 were transplanted at CRi1 or LFS1. Notably, there was no significant difference in non-relapse mortality (NRM) between individuals under and over 65 years old. Patients over and under 65 years of age had NRM of 4.4 percent, 8.4 percent, and 15.6 percent, 24.0 percent at 6 months and 2 years, respectively. The primary barrier to extended longevity after alloSCT is relapsed during the first year, especially in patients with unfavorable cytogenetics and MRD positive prior to transplantation (Figure 2).
Conclusions:
Fit older patients, especially those over 65, who get an alloSCT in CR1 can expect a 4-year survival rate of 43% and an acceptable NRM rate. Surprisingly, the NRM was not higher than for a typical younger AML sample. The greatest limiting factor to long-term survival is relapse within one year of transplantation, which reflects the biology of leukemia in these patients. Novel post-remission methods in this patient population should either complement alloSCT or compete with alloSCT’s updated outcome.