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Bernie Marini

@Berninini

16 Dec

So #twitterx doesn't throw me in Twitter jail, here are 10 #ASH21 abstracts...as HARRY POTTER characters.

I couldn't decide if I should rank based on "impactful" or "practice changing", so these are some that I think everyone should *read carefully*, and I tried to make it fun!

1. POLARIX = Severus Snape ash.confex.com/ash/2021/webpr… Why? Because of how controversial this is, and also this is a well done study. Should we change practice based on a drug without an OS or QOL benefit? I argue no. Nagini, kill. #lymsm

2. GRAAPH-2014 Study = Dudley Dursley ash.confex.com/ash/2021/webpr… Removing HiDAC from chemo in Ph+ ALL worsened outcomes. A cautionary tale that we can’t get greedy and we need RCT data like this as we “de-intensify” regimens in ALL with novel therapies like blin, TKIs, etc. #leusm

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Bernie Marini

@Berninini

15 Oct 19

PART 3! If you’re not sold on moderately intensive chemo, outcomes with HMA +/- ven also rival outcomes with CPX-351 in sAML. One could argue the control group in the CPX-351 paper should have been hypomethylating agent-based regimens!

CR/CRi rates with 10-d decitabine are consistently >50%, irrespective of sAML, age, and cytogenetics. Median OS in Blum, PNAS 2010 ~13 months. pnas.org/content/107/16…

Whether venetoclax adds anything to this remains to be seen. In the phase I/II study of HMA+ven, CR/CRi in elderly sAML was 67%, median OS NR. Wait for the phase III before you make any conclusions #oncstewardship #anothertweetorial? ncbi.nlm.nih.gov/pubmed/30361262

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Bernie Marini

@Berninini

15 Oct 19

PART 2: Enter Vyxeos (CPX-351), a liposomal encapsulation of “7+3” in a 1:5 molar ratio. This ratio is “most” synergistic in vitro (PMID18676016). Liposomal form ensures high tissue distribution (esp. bone marrow). Fun Fact: It’s purple b/c dauno is red + copper gluconate blue!

CPX-351 (n=153) was compared to 7+3 (dauno 60 mg/m2, n=156) in patients 60-75 with untreated sAML (note, did not include AML-MRC by morphology). PMID: 30024784

CPX-351 had a higher CR/CRi rate (47.7% vs. 33.3%, p=0.016), median EFS (2.53 vs. 1.31 mo., p=0.021), and median OS (9.56 vs. 5.95 mo., p=0.003). So, ~48% CR/Cri, EFS benefit of ~1 month, OS benefit of ~3.5 months. Is that a #gamechanger? What are some flaws with this study?

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Bernie Marini

@Berninini

15 Oct 19

PART 1 - Background. Vyxeos is the “winner” of the first #oncstewardship #tweetorial! There are some serious flaws in the Vyxeos data. First let’s define Secondary AML (sAML)

sAML can be divided into AML that has evolved from an antecedent heme disorder (AHD), or therapy-related AML (tAML). Per WHO, AML with myelodysplasia-related changes (AML-MRC) also includes those with MDS-related cytogenetic abnormalities and those with multilineage dysplasia

Classic agents that lead to tAML are:
1⃣XRT/alkylating agents➡️longer time to AML development (5-7 yrs)➡️associated w/ MDS-like monosomal karyotypes (deletion 5 or 7)
2⃣Topo II inhibitors➡️shorter latency (1-3 yrs)➡️associated w/KMT2A rearrangements (MLL, 11q23)
#boardquestion

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