Reduced Intensity Transplant May Improve Survival in Patients Over the Age of 40, Especially If a Sibling Donor Is Used: Pooled Analysis of 2454 Patients and 407 Transplants in the UK NCRI AML15 and AML16 Trials
Authors: Russell Nigel H , Hills Robert K. , Kjeldsen Lars , Yin John L , Craddock Charles , Burnett Alan K 
Published: October 2019

Abstract
Abstract 231
Reduced Intensity conditioning (RIC) offers a feasible option for older patients to an allogeneic stem cell transplant and to potentially benefit from a graft vs leukaemia effect. However the relative clinical benefit in AML is less clear. Since our previous experience did not show an overall survival advantage from myeloablative transplant in patients >40 years we have examined the impact of RIC allograft in 1st CR on the outcome of patients aged 40–70 years treated within the UK NCRI AML15 (2002–2009) and AML16 (2006–2012) trials compared to chemotherapy.

Methods:
Both trials offered the option of RIC transplant in CR1 for patients who were not good risk. A total of 2454 patients between 40 to 70 years entered CR (AML15: 1580 and AML16: 874) of whom 407 received a RIC (292/1580 in AML15 and 115/874 in AML16). Matched sibling transplants were given in 229, and MUDs in 178. The cytogenetic risk groups were 258 intermediate, 59 adverse, 90 not known. Follow-up is complete to 1st January 2012. Comparisons of transplant versus not are carried out using Mantel-Byar analysis to allow for time to transplant, with patients censored at the time of non-RIC allo transplant. Data from the two trials were pooled and split by age.

Results:
The OS for the 255 patients <60 yrs. was significantly superior to no transplant (53% vs 41%, HR 0.79(0.66–0.96), p=0.02). There was clear benefit in the 164 intermediate risk group patients (59% vs 44%, HR 0.67 (0.53–0.86) p=0.0008) with less evidence for the 40 who had adverse risk (16% vs 10%, HR 0.89 (0.58–1.35) p=0.6). In 152 patients 60+ yrs. the overall benefit was not significantly superior (37% vs 24%, HR 0.85 (0.68–1.06), p=0.2), there was a non-significant trend for benefit in the 94 intermediate risk group patients (43% vs 26%, HR 0.73 (0.49–1.09), p=0.3), and clearer benefit in the 19 patients in the adverse group (16% vs 3%, HR 0.57 (0.36–0.91), p=0.01). Considering the types of transplant, in the <60 group the survival benefit was restricted to sibling RIC (Sibling 61%: MUD 35%: no transplant 41%), and in the 60+ group a similar trend of borderline significance was seen (Sibling 49%:MUD 28%: no transplant 24%). In analysis by cytogenetic group, with the exception of patients over 60 yrs with adverse karyotype, sibling allograft gave consistently better survival.

Conclusion:
This pooled analysis shows that RIC allo SCT in AML 1st CR improves the survival of older patients with AML aged <60 but possibly only if a sibling donor is used. There was less benefit (sibling or MUD) for adverse risk patients. For patients aged >60 years overall benefit was less clear but there was a similar trend for benefit in intermediate risk patients. However, given the lack of statistical heterogeneity, our data does not exclude a benefit for patients with adverse risk cytogenetics or for those undergoing SCT from an unrelated donor. This observation runs counter to what we observe in patients <40 yrs, where the benefit is limited to adverse risk patients.

Disclosures:
No relevant conflicts of interest to declare.