NPM1 mutation

According to WHO, this is AML with mutated NPM1 (unless history of chemo/radio). (@BrunettiLab)

If no hx of mds or mds/mpn, current WHO still classifies it as AML with NPM1 although the comutation pattern with BCOR and SF3B1 is admittedly rare. Not sure how this changes management. Also morph dysplasia wont help as NPM1 AML often shows it. (@drwenbin_xiao)

100% agree that we need more data on co-mutation. We don't know what's the impact of this mutational pattern in the context of NPM1-mutated AML. Regardless, if unfit for intensive treatment I would go with HMA+VEN. Thanks for sharing this interesting case! (@BrunettiLab)

Interesting retrospective analysis in @BloodAdvances of #AML pts who D/C Tx after 12 mos in CR of Ven combo. Although small #’s & selection bias, those who stopped Tx after 12 mos had excellent outcomes (predom. NPM1/IDH2mut) though most were MRD-. https://t.co/L0tKWbnd8N (@LeukDocJZ)

TFR in AML with HMA + venetoclax. Interesting data for select group of patients with NPM1 and/or IDH2 mutation. https://t.co/O1ICV4O6h6 @AML_Hub (@salmanf)

#ALFlive22 #leusm Armstrong: NPM1mut AML also has similar overexpr of HoxA9 (+ other Hox genes). Menin-MLL fxn reqd for dysregd gene expr in NPM1mut and NUP98-fusion mediated AML and these leukemias also susceptible to Menin inhibitor. (@hemedoc)

Amazing paper. It truly is a new concept in cancer biology. I wonder whether something similar happens in hematopoiesis/leukemia - e.g. KIT oncogenic mutations are much more common in CBF-AML, while FLT3 mutations cluster in leukemias w/ NPM1 or NUP98 fusions (@fabiopss)

How I diagnose and treat NPM1-mutated AML: https://t.co/0IAUqF3Y5D @BloodJournal @ASH_hematology #AML (@ELShematology)

AML with APL-like immunophenotype likely to be NPM1 mutated (@JKanerMD)

This manuscript published last year also shows that NPM1-mut AML can be classified into a primitive and a committed subtype, with the primitive subtype more often presenting with an immature phenotype - CD34+/CD38lo or CD34−/CD38lo. https://t.co/5hcDPyHYmI (@fabiopss)

NPM1-mutated AML is usually CD34-negative/CD7-negative and HLA-DR variable. However, a subset of cases NPM1-mutated AML have CD34+/CD7+/HLA-DR+ - these pts have a worse outcome (@fabiopss)

AML Question! 70 year old patient with no major medical co-morbidities presents with pancytopenia. Bone marrow biopsy reveals AML with a normal karyotype. Mutation analysis reveals NPM1+ and negative for FLT3 ITD/TKD. A TET2 mutation was also identified. You recommend... (@AaronGoodman33)

Interested in thoughts from investigators,regulatory agencies and drug development sponsors that MDS and AML is truely a spectrum where 11-30% blast patients especially with driver mutations like NPM1 and FLT3 behave very similarly in terms of biology ? #leusm #mdssm (@beatalleukemia)

Dr. Sangeetha Venugopal outlines the outcomes and characteristics of pts with R/R AML who have NPM1 mutations. (@TapKadia)

At an interesting AML oral abstract session! Newly diagnosed FLT3 ITD mutated/NPM1 negative, no TP53, normal karyotype patient who is fit for chemo but age 68. What do you recommend??? #ASH21 @Dr_AmerZeidan @LeukDocJZ @Daver_Leukemia (@AaronGoodman33)

Also worth mentioning that outcomes in older patients with NPM1 mutated AML may not be the same as that observed in younger patients treated with intensive induction https://t.co/6t0JpRwCa8 (@CLachowiez)

NPM1-mut AML in older pts is a worse actor than in younger pts — would not be as enthusiastic about intensive induction. https://t.co/JlDfMQtqn1 (@matthew_mei)

Your leukemia cases are unicorns, or we are missing some details. If no dysplasia in marrow, then genetics suggest this is not related to prior therapy. If NGS is comprehensive enough and NPM1 is the only mutation, then 7+3 ->cytarabine x1; MRD-based decision on HCT vs more Ara-C (@CanerSaygin)

Leukemia question! 70-75 year old received alkylating agents as adjuvant therapy for prior cancer that is in remission Now pancytopenic. BMBx with AML. Normal karyotype. NPM1 mutated FLT3 wildtype. KPS 100%. Normal organ function. Your recommendation? (@AaronGoodman33)

Yes. NPM1-mut should be AML defining. There are some nuances like clone size, VAF, etc. in rare cases but for the most part, yes AML-defining. (@sanamloghavi)

#LLMCongress2021 | @groboz @weillcornell AZA as maintenance significantly improved OS and RFS independent of NPM1 and FLT3 mutation status, without meaningful differences in QOL, and had a higher rate of MRD response and duration of MRD negativity #leusm (@AML_Hub)

uncertain benefit of gemtuzumab in npm1 mutated. German study did not meet end point but they used more intensive induction and I think included patient up to age of 70(so may be there is trend of benefit in younger).Still I only use it in only core binding factor leukemia,Apl (@abdallahtrek)

Yes tough decision. I’m a transplanter and leukemia doc and if I were FLT3 ITD < 0.5 NPM1 mutated and achieved CR I would not want to go to allogeneic transplant and would choose HiDAC plus midostaurin consolidation for myself. (@AaronGoodman33)

7+3 + GO (D1,3,5) improves EFS in Favorable risk AML. Final results show significant EFS adv. to 7+3+GO in NPM1 mut. Also, GO did improve MRD neg CR and lowered relapse in AMLSG. So benefit may be < CBF AML but totality of data suggest improvement in NPM1 mut. (@LeukDocJZ)

The NPM1 is what is driving the cup-like shape. You can see it in NPM1/FLT3 mutated AML but you don't really see it with FLT3 mutation alone. https://t.co/4pKbD8gWah (@path_brian)

Fantastic meeting - first ever 100% Virtual @SocietyofHemOnc meeting! Beautiful talk ➡️Professor Falini from Italy 🇮🇹 on #NPM1-mutated AML: a new entity in AML since 2017 WHO classification of myeloid neoplasms. @DrHKantarjian @Daver_Leukemia @TapKadia #leusm #SOHO21 #SOHO2021 (@doctorpemm)

Alternative: CD34- CD33+ = AML with NPM1 mutation (@Snow_WhiteX)

Is it AML (MRC)? Do you have karyotype & NGS results yet? Ven aza works magic in NPM1/IDH2/IDH1 mutatedAML. If TP53 with or complx CG then chemo might be a better option. Re: fitness, I’m a fan of frailty assessment and I use it religiously. AML composite index is a good tool :) (@dgkhalaf)

IC often requires longer hospitalization. Emerging data that Ven aza may be comparable to IC in NPM1 mutated AML. CBF AML was excluded from HMA ven trial. (@VijayaRBhatt1)

After spending time in obscurity NPM1 is back 😎💪 NPM1 non-exon 12 mutations and rearrangements in AML @BloodJournal IHC, NGS and/or FISH should be used to identify rare NPM1 mutations and rearrangements. https://t.co/DN3DrOMo9d (@nvpatkar)

Cup-shaped nuclei in NPM1-mutated and FLT3-ITD+ AML. Morphologic identification can expedite molecular testing for treatment and clinical trial enrollment. #hemepath @NU_Pathology @LurieCancer @jaltmanmd (@AmirBehdadMD)

This hits hard! I’m my heart breaks every time I make a synopsis report with this diagnosis 💔 although we’ve had one long-term survivor, post allo who of all things developed a de novo NPM1 mut AML, in remission last I know. (@sanamloghavi)

Emerging WT1 mut clones contribute to relapse in NPM1 mut AML patients #USCAP2021 #USCAP2021VNI (@feldstej)

This paper helps to clarify and provide somehow a new way to flow-MRD studies in NPM1 mutated AML,... which has always been way to tricky. All I can say is 👇👇👇 (@ecoladov)

AML with NPM1 and/or FLT3 mutation (@kitagawa_yukiko)

#TCTM21 #leusm DiNardo: Genotype helps predict outcome w Venetoclax based therapy. Best resp in those w IDH, NPM1 and/or SRSF2 muts. No durable CRs w TP53 muts/loss or complex cyto. Many HMA+Ven+Agent X studies coming which hopefully will achieve durable CR in more genotypes. (@hemedoc)

How I diagnose and treat NPM1-mutated AML https://t.co/H3gqBYTbnS #AML (@BloodJournal)

Npm1 mutated leukemia (@saada_vsaada)

#ASH20 #leusm Bhatnagar: Genetic profiling found lower incidence of NPM1, WT1 and higher IDH2 in black patients with AML. Black race remained independen adverse predictor when controlling for other factors, except OS worse amongst blacks in NPM1 mut AML, esp NPM1+/FLT3-/lo. (@hemedoc)

#ASH20 #leusm Herzig: NGS method detected all ITDs found by Sanger. 63% MRD neg after consol1, 87% after EOT. Co-occuring NPM1 mut assoc w early MRD clearance. With median fup 3.4yr, VAF >median at dx and <4.7log recuction @ EOT associated with relapse (but not OS, but small n). (@hemedoc)