39th ESMO Congress 2014 Madrid, Spain 26 – 30 September 2014 Poster 979P Expedience of maintenance treatment for patients with acute myeloid leukemia younger than 65 years according to a retrospective analysis of the efficacy of two protocols S. Semochkin1,2, T. Tolstykh2, V. Ivanova3, V. Lunin3, S. Kulikova1,2, N. Huazheva3, S. Chernysh3, E. Arshanskaya2,3, M. Pochtar3, A. Tlevtsezheva3, S. Minenko2, I. Lasarev3, O. Kudriavtseva3, L. Rybkina1, E. Tihonova3, A. Rumiantsev1,2 1. Russian National Research Medical University named after N.I.Pirogov, Moscow, Russia; 2. Federal Scientific and Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev, Moscow, Russia; 3. City Clinical Hospital named after S.P.Botkin, Moscow, Russia Table 1. Demographic and Baseline Characteristics of Patients The key problem in the treatment of adult patients with acute myeloid leukemia (AML) is to prevent disease recurrences. Maintenance treatment is a controversial option for patients with acute myeloid leukemia (AML) in complete remission (CR). It is assumed that this approach minimizes residual disease and to prolong the duration of remission. The aim of this study was to examine the efficacy of prolonged maintenance chemotherapy versus intensified consolidation therapy for patients with AML. Years Disease free survival AML-2000 AML-2007 Risk of relapse Years AML-2000 AML-2007 Fig 3. Cumulative risk of relapse according to the treatment protocol Parameters AML-2000 (N=97) AML-2007 (N=101) Total (N=198) Median (range) age, years 45.61 (5.4-63.8) 39.4 (15.5-62.5) 43.9 (15.4-63.8) Sex male 47 (48.5%) 56 (55.4%) 103 (52.0%) WBC ≥ 30000/μl 27 (27.8%) 41 (40.6%) 68 (34.3%) CNS+ 5 (5.2%) 13 (12.9%) 18 (9.1%) Splenomegaly (palpable) 20 (20.6%) 33 (32.7%) 53 (26.8%) CD34 ≥ 10% 36 (92.3%) 47 (83.9%) 83 (87.4%) Median of LDH 521 426 512 U/l Type of AML Primary 91 (93.8%) 90 (89.1%) 181 (91.4%) With features of MDS 9 (8.9%) 14 (7.1%) Secondary 1 (1.1%) 2 (2.0%) 3 (1.5%) Cytogenetic group (N=44)* Good 5 (31.2%) 5 (17.9%) 10 (22.7%) Intermediate 9 (56.3%) 21 (75.0%) 30 (68.2%) Poor 2 (12.5%) 2 (7.1%) 4 (9.1%) Table 4. Prognostic value of several biological and laboratory features on the probability of CR Parameters HR (95% CI) P= AML-2000 vs AML-2007 1.15 (0.65-2.01) 0.6 Age ≥ 46 years 0.46 (0.26-0.82) 0.008 Male sex 0.79 (0.45-1.40) 0.4 WBC ≥ 50.000/μl 0.61 (0.32-1.19) 0.2 LDH ≥ 700 U/l 0.80 (0.31-2.07) 0.7 CNS+ 1.20 (0.45-3.24) Splenomegaly 0.52 (0.28-0.98) 0.043 BM blasts ≥ 30% 0.88 (0.24-3.22) 0.9 Secondary AML 0.64 (0.24-1.74) CD34+ ≥ 20% 0.21 (0.05-0.99) 0.048 Intermediate plus poor cytogenetic groups 0.71 (0.36-0.84) 0.044 PATIENTS AND METHODS A total of 198 patients with median age 43.9 years (range, 15-64) with de novo AML (non M3) which did not receive allogeneic bone marrow transplantation were enrolled in this report. TRIAL AML-2000: Of these, 97 patients during 2000-2009 were assigned to receive 2 cycles of induction “3+7” (daunorubicin 45 mg/m2 on days 1-3; cytarabine 100 mg/m2 every 12 hours [q12h] on days 1-7) and consolidation of 3 cycles “1+5” following by maintenance chemotherapy also cycles for 2 years. TRIAL AML-2007: Other 101 patients during 2007-2012 were treated 2 cycles of induction “3+7” or “3+7” plus HAM (cytarabine 3 g/m2 per q12h on days 1-3; mitoxantrone 10 mg/m2 on days 3-5) if the complete response (CR) was not documented after the first cycle. Then there were 4 cycles of consolidation HiDAC (3 g/m2 per q12h on days 1-3) without following maintenance. Fig 1. Disease free survival (DFS) AML-2000: n=57, events 29, 5-years DFS 39.6 ± 7.3% AML-2007: n=56, events 24, 5-years DFS 49.6 ± 7.3% Table 3. Adverse events III/IV degree, that were documented in the consolidation phase AE III/IV AML-2000 (N=47) AML-2007 (N=56) P= Anemia 36 (76.6%) 52 (92.9%) 0.020 Neutropenia 31 (66.0%) 56 (100%) < 0.001 Thrombocytopenia 29 (61.7%) Non-hematological toxicity Infection 38 (80.9%) 54 (96.4%) 0.012 ALT/AST 2 (4.3%) 6 (10.7%) 0.2 Nausea / vomiting 0 (0%) 3 (5.4%) Enteropathy 4 (8.5%) 14 (25.0%) 0.025 Thrombosis / hypercoagulability 1 (2.1%) 0.4 Hemorrhagic syndrome 17 (14.9%) 13 (23.2%) Overall survival Years AML-2000 AML-2007 5-year OS rate had a negative effect of age ≥ 46 years (P=0.004), WBC ≥ 50 000/μl (P=0.035) and the secondary AML (P=0.020). *Good – inv(16) or t(16;16), t(8;21), t(15;17); Intermediate – normal, +8, t(9;11), other; Poor – complex aberration ≥ 3, -5, 5q-, -7, 7q-, 11q23 – non t(9;11), inv(3), t(3;3), t(6;9), t(9;22) Table 2. Results of therapy RESULTS Conclusion Parameters AML-2000 (N=97) AML-2007 (N=101) Total (N=198) Early death 27 (27.8%) 32 (31.6%) 59 (29.8%) Refractory 13 (13.4%) 13 (12.9%) 26 (13.1%) CR 57 (58.8%) 56 (55.4%) 113 (57.1%) Relapses Early 11 (11.3%) 24 (12.1%) Later 19 (19.6%) 11 (10.9%)* 30 (15.2%) Death in CR 8 (8.2%) 6 (5.9%) 14 (7.1%) Lost follow-up 1 (1.1%) 4 (3.9%) 5 (2.5%) Alive in first CR 18 (18.6%) 22 (21.8%) 40 (20.2%) Both the concept of post-remission therapy for adults with AML which did not receive allogeneic bone marrow transplantation were demonstrated an equivalent efficacy. Maintenance treatment is an effective option for adults with AML that prolongs of DFS. In total, 57.1% of patients achieved CR. The 5-year overall survival (OS) rate was 22.3 ± 3.3%, and the disease-free survival (DFS) rate for the 113 patients who achieved CR was 36.3 ± 5.0%. No statistical difference was observed either in the 5-year OS rate (21.5 ± 4.8% vs. 23.1 ± 4.8%; P = 0.5) or in the 5-year DFS rate (39.6 ± 7.3% vs. 49.6 ± 7.3%; P=0.9) between the two trials. However, the incidence of late recurrence was higher for trial AML-2000 (19.6% vs. 10.9%; P=0.047). The median length of follow-up of surviving patients was 3.3 and 9.9 years respectively. Fig 2. Overall survival (OS) AML-2000: n=97, alive 20, 5-years OS 21.5 ± 4.8% AML-2007: n=101, alive 27, 5-years OS 23.1 ± 4.8% Intensive consolidation compared with low-intensity concolidation was accompanied by a higher frequency of adverse events III/IV degree, including neutropenia (100% vs. 68.9%; P<0.001), thrombocytopenia (100% vs. 55.2%; P=0.012) and enteropathy (29.4% vs. 0%; P=0.001). Contacts Presenting author: Semochkin Sergey 117/2, Leninsky prospekt, Moscow, Russia, 117997 Email: s.semochkin@gmail.com *P<0.05