We asked, and you answered! Here are the responses from this month’s “You Make the Call” question on treatment options for acute myeloid leukemia with persistent NPM1 mutation post-transplant.
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I would continue to watch and wait with gilteritinib maintenance.
Udit Verma, MD
Lubbock, Texas
I would prefer a watch-and-wait approach because I know (from clinical experience since literature is scarce on the subject) that NPM1 low-level MRD can persist after transplant and often does not preclude overt AML relapse.
I would perform a bone marrow NPM1 MRD test as follow-up at three and six months, and in the meantime, leave her on gilteritinib (making sure she is on the highest recommended dose).
Only in case of clear MRD molecular relapse (>0.1%) during the wait-and-watch period would I discuss donor lymphocyte infusion if she has not developed GVHD in the meantime and would also discuss switching gilteritinib for a combination of azacitidine and venetoclax.
Sarah Morin, MD, PhD
Geneva, Switzerland
I think it’s better to continue to watch and wait with gilteritinib maintenance.
Laura Dezza, MD
Vizzolo Predabissi, Italy
This case is a challenge, but there are a few options.
FLT3-positive AML before HCT has a high risk of relapse, so I suggest maintenance with gilteritinib after HCT. With the mixed chimerism (CD3+ 90%) plus MRD positivity after HCT, I would use donor lymphocyte infusion plus a hypomethylating agent to avoid morphologic relapse. It’s possible to use venetoclax, but this drug, when used with gilteritinib, can be very toxic, especially in terms of neutropenia and infections.
Hegta Rodrigues Figueiroa, MD
São Paulo, Brazil
My course of action for MRD positivity post-allogenic transplant is to start the patient on azacitidine +/- venetoclax +/- gilteritinib for a few months and then reassess the MRD; if still positive, then I’ll add donor lymphocyte infusion.
Bassam Francis Matti, MD
Baghdad, Iraq
I would opt for gilteritinib maintenance given the low level of NPM1 positivity, the absence of morphologic disease or FLT3-ITD post-HCT, and previous response to a FLT3-based regimen. I’m unsure if the outcome would change if azacitidine plus venetoclax were added.
Sudeepthi Bandikatla, MBBS
Lutz, Florida
The patient is still having a mixed T-cell lymphocyte chimerism (90%), while her myeloid chimerism is 100%. In any relapse post-HCT, if there is mixed chimerism, an effort should be made to convert it into a full donor chimerism. With gilteritinib, the synergistic effect of FLT3-ITD with NPM1 is blocked, theoretically leaving only an NPM1-driven oncogene.
In such a situation, I prefer to continue with gilteritinib, with monthly azacitidine, and dose-escalating donor lymphocyte infusions until the patient achieves a full donor T-cell lymphocyte chimerism or develops any clinical GVHD.
Tien Gen Wong, MBBS, MRCP
Ampang, Malaysia
