The University of Texas MD Anderson Cancer Center, Department of Leukemia, Houston, TX
Tapan M. Kadia , Prajwal C. Boddu , Farhad Ravandi , Guillermo Garcia-Manero , Gautam Borthakur , Michael Andreeff , Elias Jabbour , Courtney Denton Dinardo , Marina Konopleva , Naval Guastad Daver , Koichi Takahashi , Keyur Patel , Rashmi Kanagal-Shamanna , Jorge E. Cortes , Hagop M. Kantarjian
Background: TP53 mutations confer an adverse prognosis in patients (pts) with AML treated with standard chemotherapy. A recent study reported high response rates using a 10-day regimen of decitabine (DAC10) in pts with TP53-mutated (TP53-MUT) AML. The question remains whether this benefit is unique to DAC10 or whether the same benefit among TP53-MUT AML applies to other low intensity therapy (Rx). Methods: We reviewed our own experience of pts treated with low intensity Rx from 2012 - 2016. Mutation testing was performed using a whole-exome sequencing panel. We reviewed the clinico-pathologic characteristics of these pts, and compared their outcomes based on the presence/absence of a TP53mutation and by the type of Rx they received. Results: There were 131 pts in our cohort of which 33 (25%) had TP53-MUT. Pt characteristics are outlined in Table 1A. All pts were treated with low intensity Rx and were divided into the following groups: DAC10 [n=34, 26%]; 5-day decitabine, or 7-day azacytidine (DAC5) [n=39, 30%]; or cladribine+low dose araC (CLAD/LDAC) [n=58, 44%]. Response rates and OS by Rx and TP53-MUT status are summarized in Table 1B. While there was no significant difference in response rates or OS by TP53-MUT status within any of the treatment approaches, there was a trend for inferior response rates and OS among pts with TP53-MUT who received either DAC-5 or CLAD/LDAC ; this was not seen in pts receiving DAC10. Conclusions: The presence of a TP53-MUT was associated with a nonsignificant trend towards inferior outcomes among pts receiving DAC5 or CLAD/LDAC, but not among those receiving DAC10. Comparing across groups, the CLAD/LDAC combination was associated with the longest OS, and DAC10 was associated with superior outcomes compared to DAC5, in TP53-MUT cohort.
Charac. Median (range) or N, [%] | TP53– Mut | TP53– WT |
---|---|---|
N | 33 | 98 |
Age | 75 (62-90) | 72 (61-91) |
WBC | 3.2 (0.5-26.9) | 3 (0.2-77.8) |
Platelet | 28 (4-321) | 36 (2-772) |
BM Blasts | 39 (3-90) | 41 (8-88) |
Complex karyotype | 25 [76] | 10 [10] |
Diploid, -Y | 4 [12] | 42 [43] |
-5/5q- and/or -7/7q- | 23 [70] | 24 [24] |
Misc, Other Cyto | 8 [30] | 32 [33] |
N | TP53 | CR | CRp | CR/CRp (%) | Median OS | 1yr-OS % | |
---|---|---|---|---|---|---|---|
DAC5/AZA | 9 | MUT | 1 | 1 | 22 | 2.1 | 10 |
25 | WT | 10 | 1 | 44 | 5.5 | 27 | |
DAC 10 | 13 | MUT | 4 | 1 | 38 | 7.3 | 18 |
26 | WT | 7 | 1 | 31 | 7.9 | 29 | |
CLAD/LDAC | 11 | MUT | 4 | 0 | 36 | 9 | 42 |
47 | WT | 31 | 2 | 70 | 16.4 | 71 |
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