Scientific programme

OS01  Oral Session

04-May-2017 15:00 16:30

Hematologic responses with injectable HMAs may lack durability. Treatment options are limited following HMA failure. CC-486 was evaluated in 3 phase 1/2 studies that allowed patients who had received prior HMA treatment. We investigated CC-486 in patients with MDS, CMML, or AML who had received ≥2 prior injectable HMA cycles within 1 year, or 1 cycle with tolerability failure within 4 months, of starting CC-486 treatment.

CC-486 regimens were: 120-600mg x7 days (d) following one SC azacitidine cycle (75mg/m2/dx7d), or 300mg QD or 200mg BID x14d or 21d (no initial SC azacitidine), per 28d cycle.

Overall, 35 patients had failed prior-HMA treatments: MDS n=22, CMML n=2, AML n=11. For MDS/CMML and AML patients, median ages were 74.5 (range 55–84) and 71 (62–93) years, respectively. Before receiving CC-486, 11 patients (31%) had failed >1 HMA regimen, and 20 (57%) had received >4 prior-HMA cycles. Five AML patients received HMAs for antecedent MDS. Patients received a median of 5 CC-486 cycles (range 1–60). Overall response rate (ORR) was 38% (Figure 1). Of 25 patients with known prior-HMA outcomes, 4/11 refractory patients (36%) responded, including 1 CR, and 5/14 patients in relapse during/after prior HMA use responded with CC-486. ORR with CC-486 was 33% (6/18) for patients with ≥6 prior-HMA cycles. Among 13 patients who failed prior injectable-HMA regimens of ≥3 cycles within 4 months before receiving CC-486, 3 responded and 5 received ≥10 CC-486 cycles (Figure 2). Most common grade 3-4 treatment-emergent adverse events were anemia (34%), thrombocytopenia (23%), neutropenia (17%), and pneumonia (14%).

Nearly 40% of patients relapsed/refractory to prior injectable HMAs responded with CC-486, indicating HMA failure does not preclude future response with CC-486. Inadequate treatment duration was not likely the cause of prior-HMA failure; ORR with CC-486 in patients who received ≥6 prior injectable-HMA cycles was similar to ORR overall. Hypomethylating effects of injectable HMAs are transient; CC-486 can be administered for >7d/cycle to sustain hypomethylating activity and may increase azacitidine exposure to cycling malignant cells, to induce responses in patients who failed prior injectable HMAs.

G. Garcia-Manero 1, M.R. Savona 2,3, S.D. Gore 4, B.L. Scott 5, C.R. Cogle 6, T. Boyd 7, P. Conkling 8, J. Hetzer 9, Q. Dong 9, K. Kumar 10, S.M. Ukrainskyj 10, B.S. Skikne 10
1MD Anderson Cancer Center, Department of Leukemia, Houston, USA
2Vanderbilt University Medical Center, Department of Hematology/Oncology, Nashville, USA
3Vanderbilt-Ingram Cancer Center, Department of Hematology/Oncology, Nashville, USA
4Yale Cancer Center, Department of Hematology, New Haven, USA
5Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, USA
6University of Florida, Medicine/Hematology & Oncology, Gainesville, USA
7Willamette Valley Cancer Institute, Department of Hematology, Eugene, USA
8Virginia Oncology Associates, Department of Hematology/Oncology, Norfolk, USA
9Celgene Corporation, Department of Biostatistics, Summit, USA
10Celgene Corporation, Department of Hematology/Oncology, Summit, USA