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
3. GMALL 08/2013 = Hermoine Granger ash.confex.com/ash/2021/webpr… What's not to love? ❤️Risk-adapted strategy to incorporate novel tx ALL in highest risk pts, dose-adjusted PEG for risk factors. Smart, great looking trial design has to be my favorite character!
4. Time spent at home with HMA + ven therapy = Dobby, the house elf ash.confex.com/ash/2021/webpr… Small, but mighty, Dobby (like this abstract) is all about caring. I want to see more research like this on outcomes important to patients and on the patient experience. #leusm
5. HD MTX international retrospective study of 2300 high-risk DLBCL patients = Bellatrix Lestrange ash.confex.com/ash/2021/webpr… She's crazy, and it's crazy it took so long to figure out HD MTX prophy doesn't work for these pts. Hopefully we end this practice like Molly Weasley did her
6. SEQUOIA - Zanubrutinib vs. BR in newly diagnosed CLL = Neville Longbottom ash.confex.com/ash/2021/webpr… Good they compared to BR instead of like chlorambucil or something, I guess. Meh. Ok. No OS benefit, but more BTKi data upfront! Woo. Basically how I feel about Neville.
7,8,9. All 3 CAR-T trials (Belinda, Transform, Zuma) = The 3 Deathly Hallows Brothers. Why? Because we will learn much from the lessons/tale in analyzing these data - they could make us powerful...or destroy us. Can we solve the riddle? Should we move CAR-T to 2L? Much to digest!
10. Aza vs. Aza + Gilteritinib = Gilderoy Lockhart ash.confex.com/ash/2021/webpr… Lots of hype, stylish looks, ultimately does nothing helpful. Just use HMA+ven in these patients. Triplets? Not sure yet, need RCT data! #leusm
For those of you who come across the few CPX-351 (Vyxeos) #ASCO2020 abstracts still trying to spin that data positively 🙄, let me save you some time - See our 3 part #tweetorial on why you shouldn’t use this drug 🚮: #oncstewardship
cc: @AnthonyPerissi2 @Lydialbc
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
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?
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