Groundbreaking advancements in the treatment of acute leukemias and myeloproliferative/myelodysplastic neoplasms were presented at #ASH24. For our “Golden Globule” awards, we recognize standout oral abstracts that are clinically focused, globally relevant, and may have a significant impact on patient care in the near future. To select the winners, we have developed a patent-pending proprietary system that will remain forever undisclosed, allowing us, for the first time, to grant fractions of Golden Globules at our leisure. Here are the winners:
1. Choose your battles in lymphoblastic leukemia. Three studies emphasized the predictive power of measurable residual disease (MRD) and cytogenetic/molecular features in guiding clinical decisions between chemotherapy and allogeneic hematopoietic cell transplantation for adults with acute lymphocytic leukemia (ALL) — the PETHEMA LAL19 trial (Abstract 962) with “next-generation flow cytometry,” the GMALL Trial 08/2013 (Abstract 961) with polymerase chain reaction, and Abstract 727 with high-throughput sequencing. Together, these studies earned a well-deserved one-third of a Golden Globule for suggesting that patients achieving MRD negativity may avoid transplant, minimizing unnecessary treatment burdens.
2. All that glitters is not gold. The Alliance A041501 trial (Abstract 308) tried a combination of inotuzumab ozogamicin with the CALGB regimen in adolescents and young adult patients but halted enrollment due to increased toxicity in the experimental arm. Meanwhile, the control arm demonstrated favorable event-free and overall survival, reaffirming the strength of standard regimens and the importance of prioritizing safety during innovation. Negative trials deserve recognition, too. This study earns one Golden Globule.
3. More about “vitamin V” in acute myeloid leukemia (AML). Evidence supporting venetoclax-based therapy continues to grow. At #ASH24, two studies provided insights — a retrospective analysis (Abstract 450) and a randomized phase II trial (Abstract 971). Both studies compared the combination of venetoclax with hypomethylating agents (azacytidine and decitabine, respectively) to standard intensive chemotherapy. Notably, both approaches demonstrated comparable outcomes. Among younger individuals, Ven/Aza showed promising results in 28 patients treated with the regimen regardless of their fitness for intensive chemotherapy (Abstract 969). Each study earns 0.33 Golden Globules.
4. Battle of the FLT3 inhibitors. We award an entire Golden Globule to a rare head-to-head comparison of novel agents in hemato-oncology. The randomized phase II Precog 0905 study (Abstract 221) pitted midostaurin against gilteritinib plus 7+3. Interestingly, patients who received gilteritinib had increased rates of composite complete remission but not FLT3-negative responses after induction. Among post-induction FLT3-positive patients, the study revealed intriguing MRD post-consolidation dynamics, with gilteritinib showing higher rates of MRD negativity compared to midostaurin and more patients proceeding to transplant.
5. Phase III trials in pediatric AML. Even though we are adult hematologists, we recognize the importance of equity and therefore award a Golden Globule to two phase III trials exploring novel induction strategies. The Myechild 01 trial conducted a gemtuzumab ozogamicin dose-finding trial (Abstract 968), while the AAML1831 Children’s Oncology Group study (Abstract 967) used gemtuzumab ozogamicin and CPX-351 (a negative study). Each trial earns one-half of a Golden Globule.
6. Meddling with the natural history of myelofibrosis. The phase III BOREAS study (Abstract 1000) evaluated navtemadlin, an MDM2 inhibitor that “restores p53 function,” in myelofibrosis patients refractory to JAK inhibitors. Navtemadlin improved spleen volume reduction (≥35%) and total symptom score (≥50%) at week 24 compared to best available therapy and enhanced biomarkers of disease burden (Abstract 483). This study earns a macrocytic Golden Globule for combining a totally novel mechanism of action with demonstrated efficacy in a phase III trial.
7. When should we EPO in low-risk MDS? The phase III EPO-Pretar trial (Abstract 349) evaluated early versus delayed use of erythroid-stimulating agents, such as epoetin alfa (EPO), and found similar times to transfusion dependence, with no impact on survival or quality of life. This study earns one Golden Globule for reducing the need for injections in MDS patients.
8. Back to basics with ATRA in MDS. A randomized controlled trial (Abstract 663) showed that adding all-trans retinoic acid (ATRA) to decitabine improves response rates and progression-free survival in high-risk MDS. This finding highlights the value of inexpensive drug repurposing and earns a Golden Globule.
9. Teamwork makes the dream work in AML and MDS. A randomized trial (Abstract 117) showed that a collaborative palliative and oncology care model improved goals-of-care discussions, reduced end-of-life hospitalization, and enhanced quality of life. A Golden Globule goes to advancing the often-overlooked science of supportive care.
10. Honorable Mentions. While not immediately available, or clinically implementable at this time, menin inhibitors, novel agents targeting leukemic stem cells, bispecific antibodies in myeloid disorders, and even early phase data of chimeric antigen receptor T-cell therapy for ALL in first complete remission all captured our interest. Also, we foresee a bright future for myelofibrosis with the advent of new monoclonal antibodies, conjugated small interfering RNAs, anti-hemojuvelin antibodies, mixed JAK/ROCK inhibitors, and more.
Thus concludes the Golden Globule awards focused on the acute leukemia and myeloid disorders oral abstract sessions at #ASH24. Stay tuned for the lymphoma and myeloma awards in the wrap-up edition, coming to your inbox next week!
