Reduced-intensity conditioning ASCT is effective in older patients with AML

Two consecutive trials in older patients with acute myeloid leukaemia (AML) or high-grade myelodysplastic syndromes (MDS) showed improved efficacy results for allogeneic stem cell transplantation (ASCT) with reduced-intensity conditioning (RIC).

Although >65% of older (i.e. >60 years) patients with AML can achieve a complete response (CR) with intensive chemotherapy, only 20% will survive to 5 years. Thus, interventions based on preventing relapse are a priority. Options include consolidation chemotherapy, maintenance therapy, and RIC ASCT, which has made ASCT with curative intent available for older patients. Patients who achieve a CR but remain minimum residual disease (MRD)-positive are known to have an adverse prognosis and are at a higher risk of relapse following RIC transplant [1,2].

Prof. Nigel Russell (Guy's Hospital, UK) discussed the outcomes of 2 consecutive, randomised trials for patients >60 years with AML or high-grade MDS: the NCRI AML16 (NCT00454480) and AML18 trials (NCT02272478), which both included an evaluation of RIC transplant in first remission [3]. Both trials included a standard chemotherapy schedule of daunorubicin + cytarabine (DA) combined with 1 dose of gemtuzumab, followed by consolidation with DA or intermediate-dose cytarabine. AML18 also included a post-course 1 intensification randomisation to either FLAG-IDA, DA + cladribine, or DA alone for those patients not in MRD-negative remission. Patients in remission with unfavourable risk cytogenetics could undergo a RIC transplant. AML16 enrolled 983 patients in first remission aged 60–70 years, with 144 (15%) receiving RIC transplant. AML18 included 648 patients in first remission aged 60–74 years, with 201 (31%) receiving a RIC transplant.

At 5 years, AML16 results demonstrated clear benefits for RIC compared with chemotherapy: overall survival (OS) was increased (37% vs 20%; P<0.001), relapse risk was reduced (43% vs 83%; P<0.001), while non-relapse mortality was increased (39% vs 11%; P<0.001). Survival in RIC-treated patients was not different between those with sibling (44.2%) or unrelated donors (33.6%; P=0.3). These results were confirmed by multivariate Mantel-Byar analysis of survival by risk groups.

In AML18, 648 out of 847 (76%) patients achieved complete remission and the outcome for post-course 1 MDR-positive patients was not different from MRD-negative patients. Interim analysis confirmed the AML16 result of a benefit for transplant with 3-year survival from remission of 48.0% versus 37.4% (P=0.027). Most transplants were performed after courses 2 or 3. Overall, 120 out of 222 (59%) of patients who were MRD-positive post-course 1 became MRD-negative post-course 2 and the benefit for transplant was greater in these patients compared with those who remained MRD positive.

To conclude, 2 consecutive trials in over 1,500 older AML patients demonstrated a consistent benefit for RIC transplant in first remission, independent of post-course 1 MRD status. The overall improvement in outcome for post course 1 MRD-positive patients in AML18 compared with AML16 may reflect treatment intensification post-course 1 and the impact of the increased uptake of RIC transplant in AML18.

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   1. Freeman SD, et al. J Clin Oncol 2013;31(32):4123–31.
   2. Hourigan CS, et al. J Clin Oncol 2020;38(12):1273–83.
   3. Russell N. Sequential NCRI AML trials show consistent benefit for RIC transplant in CR1 for older patients >60 years that is independent of MRD status after first induction. S130, EHA 2021 Virtual Congress.

 

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Posted on 5 August, 202116 February, 2024