What are your top takeaways from ASH 2023?

Gene therapy for sickle cell disease and beta thalassemia.

This was the first approval of CRISPR/Cas-based therapy in humans. Ex-vivo engineering of isologous hematopoietic stem cells followed by their reinfusion after myeloablative conditioning led to induction of 40-50% fetal hemoglobin in patients with sickle cell disease and very high concentrations of fetal hemoglobin in transfusion-dependent beta thalassemia with a functional cure of these diseases after up to 5 years of follow up.

1. IsKia study: Best MRD negativity rates of any front-line study especially for high risk myeloma.
   
   
2. PEGASUS study: Randomized Phase 3 study confirms findings from GRIFFIN study showing superiority of 4-drug vs 3-drug combo prior to transplant.
   
   
3. Talquetamab + pomalidomide in myeloma: first trial to report on combo IV bispecific with IMID.

MDS and AML

1. Abstract 319: Efficacy and Safety of Venetoclax in Combination with Azacitidine for the Treatment of Patients with Treatment-Naive, Higher-Risk Myelodysplastic Syndromes.

Using the recommended phase 2 dose schedule (regimen including 14 days of venetoclax in each 28-day cycle), upfront treatment of high-risk MDS with a combination of azacitidine and venetoclax achieved an objective response in over 80% of patients. This included complete responses and hematologic improvement. Intere...

1. The best presentation was the IRON REVOLUTION (Auerbach, DeLoughery, Powers): Lots of new, clarifying, and dispelled errors of the past.
2. The most inciteful presentation was the siRNA based therapeutics targeting VWD mutated genes as a new therapeutic, by Jeroen Eikenboom. This was in Denise Sabatino's Scientific Subcommittee session!
3. And, although not my area, I thought Dr. Rezvani's E. Donnall Thomas lecture on her novel approach to BM transplantation was amazing!

1. Phase 3 Randomized Study of Daratumumab (DARA) + Bortezomib, Lenalidomide, and Dexamethasone (VRd) Versus Vrd Alone in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) Who Are Eligible for Autologous Stem Cell Transplantation (ASCT): Primary Results of the PERSEUS Trial

The results of the PERSEUS trial were eagerly awaited by the myeloma community and so this would be an easy choice for a top ASH abstract. This study essentially validates the gradual change in practice that has take...

1. MANIFEST-2
   
   One of the largest trials ever done in this disease, MANIFEST-2 enrolled 431 patients with JAK inhibitor-naïve, DIPSS intermediate-1 (60%), intermediate-2 (30%), or high risk (10%) myelofibrosis. Patients were randomly assigned (1:1) to receive ruxolitinib and pelabresib (BET inhibitor) or ruxolitinib and placebo. Pelabresib or placebo was administered orally on days 1-14 of a 3-week cycle. The starting dose of ruxolitinib was one dose level lower than what would be indicated by the ...

1. Abstract 970 - A Phase IIb trial investigating intensive chemotherapy in comparison to hypomethylating agent + venetoclax in younger adults with newly diagnosed AML. The primary endpoint of CR/CRi was higher in the HMA + Venetoclax cohort which stimulates further discussion about which patients benefit most from intensive chemotherapy versus an HMA + Venetoclax strategy.
   
   
2. Abstract 833 - A Phase II study of an all-oral regimen for AML comprising of ASTX727 (oral decitabine + cedazuridine) + venet...