Outcomes with lower intensity therapy in TP53-mutated AML.

Authors

null

Tapan M. Kadia

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

Organizations

The University of Texas MD Anderson Cancer Center, Department of Leukemia, Houston, TX, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, The University of Texas MD Anderson Cancer Center, Houston, TX, The University of Texas MD Anderson Cancer Center, Department of Hematopathology, Houston, TX

Research Funding

NIH

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– MutTP53– WT
N3398
Age75 (62-90)72 (61-91)
WBC3.2 (0.5-26.9)3 (0.2-77.8)
Platelet28 (4-321)36 (2-772)
BM Blasts39 (3-90)41 (8-88)
    Complex karyotype25 [76]10 [10]
    Diploid, -Y4 [12]42 [43]
    -5/5q- and/or -7/7q-23 [70]24 [24]
    Misc, Other Cyto8 [30]32 [33]
NTP53CRCRpCR/CRp (%)Median OS1yr-OS %
DAC5/AZA9MUT11222.110
25WT101445.527
DAC 1013MUT41387.318
26WT71317.929
CLAD/LDAC11MUT4036942
47WT3127016.471

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Track

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Sub Track

Acute Leukemia

Citation

J Clin Oncol 35, 2017 (suppl; abstr 7017)

DOI

10.1200/JCO.2017.35.15_suppl.7017

Abstract #

7017

Poster Bd #

217

Abstract Disclosures

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