In an international study of 366 patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), researchers identified several prognostic factors for patients who would most benefit from induction chemotherapies as a bridge to allogeneic hematopoietic cell transplantation (HCT) after hypomethylating agent (HMA) failure.
The retrospective analysis of induction response rate and survival included 307 patients with MDS and 59 patients with AML. Patients with MDS had a median age of 64 years (range, 22-85 years). For those with available IPSS scores, 68% (n = 161) had higher-risk MDS (intermediate-2 or high risk) at initial diagnosis.
Induction chemotherapy led to an overall response rate (ORR) of 41%, median overall survival of 10.8 months and allogeneic HCT in 40% of responders. When comparing chemotherapy regimens, patients who received intermediate- to high-dose cytarabine (IDAC) had a significantly higher ORR of 64%, compared to 39% for 7+3 and 34% for PNA (p = 0.04). Patients receiving IDAC were also significantly more likely to bridge to allogeneic HCT (IDAC, 64%; 7+3, 37%; PNA, 23%, p < 0.01). Participants who received IDAC were significantly younger, heavily pre-treated, and nearly 20% with a prior HCT compared with groups receiving other induction regimens.
There was no difference in the median OS, 8-week mortality or median cumulative incidence of relapse between the three induction groups. However, in a landmark analysis, patients with MDS who bridged to allogeneic HCT (n=51) had an improved OS when compared to non-transplanted patients of 23 months vs 10 months (p < 0.01). Patients with AML had improved OS of 20 months vs 6 months (p< 0.01).
Prognostic factors leading to a lower response in MDS included adverse cytogenetics (odds ratio [OR], 0.46, p = 0.01), age ≥65 years (OR, 0.47; p < 0.01), and use of non-IDAC regimens (OR, 2.91, P=. 01). Patients without these risk factors had a response rate of 72%; median OS of 27 months and increased probability of undergoing HCT of 72%. The lower number of AML patients limited the researchers’ conclusions.
The researchers "strongly emphasize the need to prioritize clinical trial participation for all patients experiencing HMA failure, and we should consider using induction chemotherapy as a backbone for novel agent evaluation for patients able to tolerate this approach."