Page 23 - 2021_10-Haematologica-web

Dose intensity for induction in AML
Figure 1. Selection of initial therapy for acute myeloid leukemia. *PS: Performance Status; HMA: hypomethylating agent; XRT: radiation; Ven: venetoclax; LDAC: low- dose ara-C; AML-MRC: acute myeloid leukemia with myelodysplasia-related changes; GO: gemtuzumab ozogamicin.
While looking hopefully to the future, our practice as of now (summarized in Figure 1) is to pursue IC with 7+3 in patients less than 70 years old with no criteria for exclu- sion from induction. We add GO to 7+3 for all patients with CBF-AML, as long as their liver function is adequate, and FLT3 inhibitors to 7+3 from day 8-21 for all FLT3- mutated patients. For patients over 70 years old we prefer azacitidine/venetoclax as induction unless they have high- ly proliferative disease (i.e., extreme hyperleukocytosis) or have cytogenetics or mutations suggestive of chemore- sponsiveness (CBF or NPM1). We suspect that a potential third practice-changing triplet could come in the form of venetoclax, cytarabine, and an anthracycline, which has shown early success in NPM1-mutated AML. For patients younger than 70 years old, we would consider azaciti- dine/venetoclax if they have secondary AML, adverse-risk AML including monosomal karyotype, complex kary- otype or MDS-defining cytogenetics. For TP53-mutated
AML patients we recommend a clinical trial if available until the next practice-changing treatment is approved. As leukemia physicians we are fortunate to be working in an era of remarkable progress. First and foremost, we know that the future will yield even more dramatic changes to the treatment of AML than we have been fortunate to wit- ness in the past few years.
Disclosures
SML has received research support for her institution from Onconova, Kura, Hoffman La Roche, Ariad, and Biosight; and honoraria from Abbvie, Syrox, Jazz, Daiichi-Sankyo, Pfizer, Bristol-Myers Squibb, Acceleron, Agios, and Loxo Oncology. SRM has received research support from Gilead and Aprea.
Contributions
SML and SRM performed the literature review, evaluated the data, and wrote the manuscript.
References
1. Yates JW, Wallace HJ Jr, Ellison RR, Holland JF. Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep. 1973;57(4):485-488.
2. Bolanos-Meade J, Karp JE, Guo C, et al. Timed sequential therapy of acute myeloge- nous leukemia in adults: a phase II study of retinoids in combination with the sequential administration of cytosine arabinoside, idarubicin and etoposide. Leuk Res. 2003;27 (4):313-321.
3. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J
Med. 2020;383(7):617-629.
4. Juliusson G, Swedish AML Group. Most 70-
to 79-year-old patients with acute myeloid leukemia do benefit from intensive treat- ment. Blood. 2011;117(12):3473-3474.
5.Juliusson G, Billstrom R, Gruber A, et al. Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival. Leukemia. 2006;20(1):42-47.
6. Lowenberg B, Zittoun R, Kerkhofs H, et al. On the value of intensive remission-induc- tion chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a ran- domized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol.
1989;7(9):1268-1274.
7. Lang K, Earle CC, Foster T, Dixon D, Van
Gool R, Menzin J. Trends in the treatment of acute myeloid leukaemia in the elderly. Drugs Aging. 2005;22(11):943-955.
8.Medeiros BC, Satram-Hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94(7):1127-1138.
9. Baz R, Rodriguez C, Fu AZ, et al. Impact of remission induction chemotherapy on sur- vival in older adults with acute myeloid leukemia. Cancer. 2007;110(8):1752-1759.
10.Puts MT, Costa-Lima B, Monette J, et al. Medication problems in older, newly diag-
haematologica | 2021; 106(10)
2551