General AML

An Editorial on Acute Myeloid Leukemia: Evidence Weak for Maintenance in Adults in CR

Rashidi A. of the Washington University School of Medicine St. Louis and his colleagues published a systematic review in the journal Blood in August 2016 exploring evidence that exists for the benefits of low-intensity maintenance in patients who are in CR after consolidation with the 7+3 cytarabine-idarubicin regimen or allogeneic hematopoietic stem cell transplant (allo-HCT). Maintenance therapy has been of use in other types of cancers including Acute Promyelocytic Leukemia (APL), therefore it is of interest in AML where more therapeutic advances are needed.

The researchers identified two specific cases of patients that may benefit from maintenance therapy:

64 year old male, cytogenetically normal AML (no FLT3-ITD, NMP1 or CEBPA mutations), achieved morphologic CR after induction chemotherapy. Declined allo-HCT, undertaking 3 cycles of consolidation chemotherapy with high-dose cytarabine at 3 g/m2 for 6 doses per cycle.

41 year old female, AML with deleterious FLT3-ITD mutation, karyotype otherwise normal. Morphologic CR after 7+3 induction, consolidation with myeloablative T-replete allo-HCT. Cells were donated from her HLA-matched brother. Evidence of full donor chimerism after one month and no evidence of relapse or graft versus host disease (GVHD).

Out of 595 studies found by Rashidi A. and his colleagues, spanning 40 years of research, 13 randomized studies had groups similar regarding previous treatment of had adjusted data and 37 were allocated as “alternative-design trials” (studies with dissimilar populations between treatment groups or unadjusted data to account for between-group differences, and studies which used non-standard intensification and consolidation regimens).

Maintenance after consolidation

The researchers do not recommend maintenance therapy following adequate induction and consolidation except when using midostaurin during induction, consolidation and maintenance in FLT3 mutated cases of AML.

Maintenance after allo-HCT

Maintenance theoretically contributes to cure by maintaining disease burden until the immunologic effect of graft versus leukemia becomes dominant, resulting in eradication of any residual disease.

 No randomized controlled trials have yet been undertaken to explore maintenance after allo-HCT; in their absence the Rashidi A. et al. do not recommend maintenance after allo-HCT outside of well-designed clinical trials and encourage participation in trials of maintenance after allo-HCT.

Neil Osterweil, an author for Medpage ASCO (in the ASCO reading room) reported on these findings in September 2016 and Dr Amitkumar Mehta of the University of Alabama at Birmingham, provided a thought-provoking critique on the role and benefits of maintenance therapy in patients with AML who are in CR following therapy with curative intent.

Dr Mehta states that the role and relative benefits of maintenance therapy in AML based on this systematic review is unclear as the available data are not robust and are inconclusive. There is a need for more consistent clinical trial design, more expansive efficacy parameters and the greater inclusion of different patient types, especially for the use of maintenance therapy post-allo-HCT. Nonetheless, Mehta concludes this critique more optimistically by commenting on the potential benefits of novel agents such as small molecule inhibitors and immunotherapy.

Please read the full editorial and critique here

Please find the full journal article published in Blood here

References
  1. Rashidi A. et al. Maintenance therapy in acute myeloid leukemia: an evidence-based review of randomized trials. Blood 2016 Aug 11; 128(6):763–773. DOI: 10.1182/blood-2016-03-674127. Epub 2016 Jun 27.
  2. Osterweil N. & Mehta A. AML: Evidence weak in adults in CR. MedPage Today®http://www.medpagetoday.com/reading-room/asco/hematologic-malignancies/60495 [Accessed 12/10/16].
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