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And the ASHcademy Award Goes to...: Rolling Out the Red Carpet for the Best of ASH Malignant Sessions

December 16, 2021

Rolling Out the Red Carpet for the Best of ASH Malignant Sessions 

Natasha Szuber, MSc, MD

Dr. Natasha Szuber (@NatashaSzuber) is a hematologist-oncologist at Maisonneuve-Rosemont Hospital, University of Montreal in Quebec, Canada, specializing in myeloid disorders, particularly myeloproliferative neoplasms, and has further interests in clonal hematopoiesis and iron metabolism. She received her MSc at McGill University in Montreal, her MD at University of Montreal, and did her Advanced Hematology Myeloid Fellowship at Mayo Clinic in Rochester, Minnesota. Dr. Szuber remarked that she was “born, raised, and currently still residing in Montreal…It's a beautiful, vibrant city if you can look past the orange construction cones and innumerable potholes!” 

While Dr. Szuber is “relatively new” to the ASH family, she is looking forward to collaborating further in coming years and was just selected to participate in the ASH Clinical Research Training Institute this year. Fun fact: Dr. Szuber enjoyed a “past life as an aspiring rock n' roll star, recorded three albums, and toured with my band across Canada before finally surrendering to the call to med school.” 

 

The lights dim. The uncomposed hovering of the orchestra pit violins tuning-up dreamily fades. You look to your left, then to your right — you’re surrounded by luminaries, ASH-lebrities as they would be (you know, the Meryl Streeps of hematology), and you are starstruck. Ladies and gentlemen, welcome to the roundup of the 63rd ASH Annual Meeting “Best of Malignant” Awards ceremony. Your hosts for the Tuesday afternoon premier event were none other than Drs. Benjamin Kile and Omar Abdel-Wahab, who reveled in what an exciting year it had been, and this, despite the global pandemic. Emerging themes, according to Dr. Abdel-Wahab (pictured), included “Practice-changing updates and developments in chimeric antigen receptor-T cell (CAR-T) therapy in B-cell malignancies, advances in understanding and targeting the immune microenvironment, advances in molecularly targeted therapeutics for genetically defined subsets of leukemias, and single-cell multi-omics analyses in myeloproliferative neoplasms (MPN).” We’ve rounded out their picks with a few of our (aka, ASH News Daily’s) People’s Choice Award winners, as we celebrate excellence in malignant hematology. So, get comfortable (as comfortable as you can in Louboutin  heels or a narrowly-tailored tux… or if joining virtually, avail yourself to the convenient plushness of your sweatpants), munch on the chips Jimmy Kimmel left under your seats, root for your favorites, and enjoy the show! 

And the winners are… 

From the “Lymphoma” category 

  • Greatest potential to shake-up frontline care” goes to the POLARIX study (LBA-1) from Dr. Hervé Tilly and colleagues, examining the combination of CD79b-targeting polatuzumab vedotin, with rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) versus the current standard of care (R-CHOP; vincristine [O]) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL). With pola-R-CHP outperforming the latter with a comparably safe toxicity profile, could this herald the dethroning of R-CHOP as standard frontline in DLBCL? Cue the impassioned debates…  
  • The Plenary Scientific Session introduced the “Most innovative biomarker application” laureate (abstract 6), spotlighting the use of circulating tumor DNA as a noninvasive, biopsy-free tool for disease detection and monitoring in patients with central nervous system lymphoma, filling a major unmet need and representing a potential breakthrough in diagnosis and management.  
  • Two studies received awards for “Outstanding achievements in CAR-T therapy.” ZUMA7 (abstract 2; back for an encore from the Plenary) and TRANSFORM (abstract 91) studied CD19-directed CAR-T, respectively axicabtagene ciloleucel and lisocabtagene maraleucel, versus standard-of-care in patients with relapsed/refractory (R/R) DLBCL. Dr. Abdel-Wahab explained, “These were both randomized, global, multicenter phase III studies… which rigorously demonstrated benefit of CAR-T over standard therapies.” These data “heralds a paradigm shift” as per Dr. Frederick Locke of ZUMA-7, begging the question, will CAR-T become the “new” transplant? 

From the “Multiple myeloma” (MM) category 

  • The theme of CAR-T therapy also prevailed on the MM scene. Awards for “Advancements of CAR-T therapy in multiple myeloma” were accorded to three studies. First, the update of CARTITUDE-1, a phase Ib/II study of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR-T, in heavily pre-treated patients with R/R MM (abstract 549), relayed deep and lasting responses after 18 months of follow-up. Second, LocoMMotion (abstract 550), serving as an indirect external control cohort for CARTITUDE-1 and representing the first prospective real-world study in this subset, disclosed superior outcomes with cilta-cel versus standard regimens, highlighting the potential of this agent. Finally, the update from the phase I CRB-402 study (abstract 548) assessing a BCMA-targeted CAR-T (bb21217) with added PI3K inhibitor in multi-treated R/R MM subjects, revealed promising results. Both efficacy and safety data were favorable, supporting the hypothesis that persistence, at least in terms of enriched memory-like T cells associated with bb21217, pays off.  

From the “Leukemia” category 

  • Top prospective game-changer in pediatric leukemia” was bestowed upon a phase II study from the Interfant Network (abstract 361), assessing the impact of adding blinatumomab to the Interfant06 backbone in infants with newly-diagnosed KMT2A-rearranged acute lymphoblastic leukemia (ALL). Dr. Abdel-Wahab enthused, “This is an international study which might change the paradigm of treatment of infants with KMT2A-rearranged ALL.” 
  • Outcomes from the QUAZAR AML-001 trial of oral azacitidine (AZA) maintenance in acute myeloid leukemia (AML; abstract 804) garnered the honor of Highest achievement in application of biomarkers, molecular markers and minimal residual disease (MRD),” demonstrating independent prognostic ramifications of oral AZA therapy, NPM1 and FLT3 mutations at diagnosis, and MRD status on overall survival. 
  • “Best special effects exploiting phagocytosis” went to the phase I/II study of AZA coupled with venetoclax (VEN) plus magrolimab (Magro), an anti-CD47 antibody that, as authors simplified, “blocks the ‘don’t eat me signal’ on macrophages,” in older/unfit or high-risk patients with AML. This commandeering of macrophages to eradicate AML cells yielded enhanced responses, even in TP53-mutated populations, and while still at an early phase of investigation, this is a combination to watch out for. 
  • Greatest performance by a targeted therapeutic agent in AML” was presented to the phase III AGILE trial (abstract 697), which broke ground using oral IDH1 inhibition (ivosidenib) coupled with AZA in subjects with de novo IDH1-mutated AML, with remarkable results. 

From the “Myeloproliferative Neoplasms (MPN) and Myelodysplastic Syndromes (MDS)” categories 

  • The “Breakthrough star in MDS” accolade went to the landmark molecular international prognosis scoring system (IPSS-M) for MDS (abstract 61). Leading to the restaging of nearly 50 percent of patients with MDS, this work illuminated the role of select mutations in MDS risk stratification, endeavoring to become the new standard for prognostic assessment.  
  • The winner for “Best targeted takedown of TP53” was the long-term follow-up and combined phase II results of eprenetapopt (APR-246) and AZA in patients with TP53-mutated myeloid malignancies (abstract 246). This multicenter, international study demonstrated favorable tolerability and high response rates, offering promise to a population with conventionally unfavorable outlook.  
  • The “Excellence and pioneering in MPN” award was graciously presented to Dr. Ayalew Tefferi and his collaborators for their novel “Triple AAA” risk model for essential thrombocythemia (ETabstract 238). While leukocytosis has long been recognized as prognostically deleterious in MPN, this work finally addressed the independent contribution of absolute lymphocyte count with ground-breaking conclusions, branding a novel, clinically applicable risk model for ET and introducing the concept of immune profiling as an additional predictive tool. Brava! 
  • The “Treatment-free remission (TFR) trailblazer” was attributed to the final analysis of the largest TFR trial, EURO-SKI (European Stop TKI), reporting 46 percent of patients still in molecular recurrence- and treatment-free survival after three years (abstract 633). 

From the “Crossover Myeloid/Lymphoid Rising Star” category 

A golden stASHtuette (forced ASH-meets-Oscar wordplay too irresistible to pass up) was granted to the phase II study of pemigatinib (FIGHT-203; INCB054828) in patients with fibroblast growth factor receptor 1 rearranged myeloid/lymphoid neoplasms (abstract 385). Dr. Abdel-Wahab lauded this work as “very interesting, as it is a clinical trial studying a highly effective targeted therapy for an extremely rare, molecularly defined entity, proper recognition of which is exceedingly important.”  

From the “Advances in Therapeutics for Chronic Graft-Versus-Host Disease (cGVHD)” category 

Dr. Abdel-Wahab commended the phase I/II trial of axatilimab (abstract 263), a CSF-1R humanized antibody, for its “impressive and promising” results, leading to best overall response rates of up to 70 percent in subjects with cGVHD following two or more lines of systemic therapy. Next to take the stage will be the global randomized AGAVE-201 trial, which has already started enrollment and whose results will be eagerly anticipated. 

From the “Cutting-Edge Technology” category 

Single-cell genomics was definitely the “it” kid at this year’s Awards, playing a starring role in numerous applications, from elucidating the landscape of TP53-mutant myeloid neoplasms (abstract 3), to defining the clonal architecture of leukemic transformation of MPN (abstract 56), to exploring BCMA-targeted CAR-T effects on tumor genomics in MM (abstracts 326). Take it all in, single-cell, it’s your time to shine!  

As the curtains close and the audience abuzz with gossip spills out into the hallways of the Convention Center (hardly distinguishable from the Dolby Theatre at this point), we take a moment to look past the glamor, the brio, the dazzle – and honor these members of ASH royalty for their hard work and fine achievements. And, yes, we congratulate the winners, but also are fortunate to belong to a community where all nominees — all contributors, everyone — from the stars to the set designers, sound editors, and gaffers, are all valued, appreciated, and applauded. So as awards season comes to a close here at ASH, we set our sights on next year, as we know… the show must go on! P.S.: Catch you at the Vanity Fair after-party? 

Dr. Szuber indicated no relevant conflicts of interest. 

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