PB1728 CLINICAL CHARACTERISTICS AND THERAPEUTIC RESULTS OF PRIMARY REFRACTORY ACUTE MYELOID LEUKEMIA IN OLDER PATIENTS. A STUDY ON 118 CONSECUTIVE PATIENTS.
Authors: F. Ferrara, G. Rossi, O. Vitagliano, F. Lessi, E. Borlenghi, M. Laurino
Journal: HemaSphere (2019)

Background: There is no universally agreed definition of primary refractory acute myeloid leukemia (AML) and optimal treatment modalities are still ill defined, particularly in older patient population. Aims: We describe clinical characteristics and therapeutic results from a series of 118 consecutive elderly patients with AML classified as primary refractory on the basis of achievement of less than partial response according to ELN criteria following administration of intensive induction chemotherapy aimed at complete remission (CR) achievement. Methods: There were 72 males and 46 females, with a median age of 68 years (range: 61‐79). In 40 patients (34%), a previously diagnosed myelodysplastic syndrome preceded the onset of AML. Sixty‐six patients (56%) had adverse karyotype, 52 normal (43%) and 1 (1%) AML with t(8;21) translocation. In the group with normal karyotype, 38 patients were classified as intermediate and 14 as adverse risk category according to European LeukemiaNet criteria. Induction treatment included anthracyclines and cytarabine in 74 cases, and fludarabine based regimens in the remaining 44. In all patients, more than 50 % of blasts were found at bone marrow evaluation after induction. Subsequent therapy included salvage intensive chemotherapy (ISC) based on intermediate‐high dose cytarabine in 74 patients (63%), hypomethylating agents (HMAs) in 26 (22%), 22 azacitidine and 4 decitabine, and best supportive care (BSC) in 18 (15%). Therapeutic choice was mainly based on eligibility to allogeneic stem cell transplantation (SCT), ECOG performance status, logistic reasons and personal physician attitude. Results: Following intensive salvage chemotherapy, CR was achieved in 28 patients out of 74 intensively treated (38%) and 16 of them did actually receive SCT. No CR was observed with HMAs, but 2 patients had a reduction of bone marrow blasts at less than 10 % and received SCT. The median survival for the whole patient population was 7.7 months and there were no significant difference according to different treatments (9 months for ISC, 8 for HMAs and 5 months for BSC, p.0.3). The outcome was also similar for patients with normal karyotype (8 months) vs unfavorable karyotype (7 months),p:0.23 and patients with previous MDS (7 months) vs. de novo AML (8 months), p:0.43. Achievement of CR and SCT were the only factors significantly related to a better outcome in univariate and multivariate analysis (median survival for patients achieving CR or not: 18 months vs 7 months, respectively, p: &lt; 0.001; 18 months for allografted patients vs. 6 for not allografted, p:0.001). Summary/Conclusion: We conclude that primary refractory AML in older patients is characterized by an extremely poor outcome; SCT represents the only chance for long‐term survival and ISC should be considered only in transplant eligible patients (figure). HMAs represent a reasonable option and, occasionally, a bridge to SCT. The possibility of administration of new molecularly targeted new agents is expected to lead to significant improvement of clinical outcome in this prognostic adverse patient category. image