ESMO East 2024: Leukemia Updates with Dr Liat Dagan

Presenter:

Liat Nadav Dagan, MD PhD, Lynn Cancer Institute

Conference:

2024 ESMO East

At the 2024 ESMO East Conference, Dr Liat Dagan from Lynn Cancer Institute highlighted a series of abstracts focused on leukemia from this year’s annual European Society for Medical Oncology (ESMO) Congress, with an emphasis on optimizing outcomes, emerging treatment options and novel therapeutic strategies. 

1. Flumatinib Plus Chemotherapy in Philadelphia-Positive ALL (Abstract 829P)

This single-center, retrospective study evaluated the use of flumatinib, a tyrosine kinase inhibitor (TKI) approved in China, in combination with multi-agent chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

• Study Population and Methods:
  The study included adult patients treated between 2020 and 2023. Outcomes such as complete remission (CR) and minimal residual disease (MRD) negativity were assessed over a median follow-up of 41.1 months.

• Key Findings:

• The 3-month and 6-month CR rates were 100% and 93.3%, respectively.

• MRD negativity rates improved progressively, reaching 90% at 6 months.

• Achieving MRD negativity or CR significantly enhanced overall survival (OS).

• The 3-year OS was 70.8%, with significantly improved outcomes observed in patients who underwent allogeneic stem cell transplantation (94.1% vs. 54.8%, P=0.0057).

• Achieving a major molecular response (MMR) or complete molecular response (CMR), however, showed no additional OS benefit.

• Conclusion:
  Flumatinib, combined with chemotherapy, was a highly effective treatment for newly diagnosed Ph+ ALL, with MRD negative status serving as a key predictor of survival.

2. Hospital Volume and Survival in AML Patients Treated with Intensive Chemotherapy

This Netherlands-based study explored the relationship between hospital case volume and survival in acute myeloid leukemia (AML) patients receiving intensive induction chemotherapy.

• Study Design:
  The cohort included 1,761 patients treated between 2014 and 2018 at 24 qualified hospitals. Patient demographics, disease characteristics, and socioeconomic factors were adjusted in statistical analyses.

• Key Results:

• Higher hospital volume correlated with better survival. Each additional 10 patients treated per year was associated with an 8% reduction in mortality risk (hazard ratio [HR] = 0.92, P=0.01).

• Hospital volume did not affect 30-day overall survival (OS) but significantly influenced 100-day OS (HR = 0.91, P=0.05).

• Survival variability decreased as hospital volume increased, highlighting a potential centralization benefit.

• Conclusion:
  High hospital volume was associated with improved longer-term survival in AML patients, supporting the centralization of intensive chemotherapy at experienced centers.

3. Rovadicitinib Versus Hydroxyurea in Myelofibrosis

This phase 2, double-blind trial compared the efficacy and safety of rovadicitinib, a novel JAK-ROCK inhibitor type therapy, to hydroxyurea in patients with intermediate- to high-risk myelofibrosis (MF).

• Study Design and Population:
  Patient who had not previously been treated with a JAK inhibitor (JAK inhibitor-naïve) were randomized to receive rovadicitinib or hydroxyurea. Primary and secondary endpoints included spleen volume reduction (SVR) ≥35% and symptom improvement at 24 weeks.

• Key Findings:

• Rovatiditinib significantly improved SVR rates (58% vs. 22% with hydroxyurea).

• Symptom improvement ≥50% was observed in 61% of rovadicitinib-treated patients compared to 45% of patients in the hydroxyurea group.

• Adverse events included cytopenias (e.g., anemia, thrombocytopenia) but were generally manageable.

• Conclusion:
  Rovatiditinib demonstrated superior efficacy over hydroxyurea in spleen volume reduction and symptom control, offering a promising first-line option for patients with high-risk MF.

4. FLT3-ITD Induces Immune Escape in AML via CD47 Upregulation (Abstract 824P)

FLT3-ITD mutations, which are seen in about 30% of acute myeloid leukemia (AML) cases, are associated with poor prognosis. This preclinical study investigated the immune-evasion mechanisms driven by FLT3-ITD and evaluated potential therapeutic strategies.

• Mechanistic Insights:

• FLT3-ITD mutations led to elevated CD47 expression, mediating a "don’t eat me" signal that reduced macrophage phagocytosis of AML cells.

• Transcription factor HOXB5 was identified as a key regulator of CD47 overexpression.

• Therapeutic Findings:

• Combining FLT3 inhibitor quizartinib with a CD47-targeting antibody enhanced macrophage phagocytosis in vitro and reduced leukemia burden in mouse models.

• Conclusion:
  Targeting FLT3-ITD and CD47 pathways synergistically improves antitumor immunity, providing a rationale for combinatorial therapies in FLT3-ITD AML.

5. Timdarpacept Plus Azacitidine for Chronic Myelomonocytic Leukemia (CMML)

Timdarpacept, a bispecific antibody targeting CD47 and activating macrophages, was combined with azacitidine in this phase 2 trial to treat high-risk CMML.

• Study Design:
  High-risk, non-transplant-eligible patients received timdarpacept plus azacitidine, with response rates and safety as primary endpoints.

• Key Results:

• The overall response rate at six months was 84%, with 46% achieving complete remission.

• Blast reductions were observed in the majority of patients, accompanied by durable treatment responses (median 15 months).

• Grade 3–4 adverse events were mainly hematologic but were comparable to azacitidine monotherapy.

• Conclusion:
  Timdarpacept showed high efficacy and acceptable safety in CMML, supporting its further investigation as a therapeutic option for high-risk patients.

Summary

The abstracts from this year’s ESMO, as selected by Dr Dagan, highlight the range of new advances in leukemia and related hematologic malignancies such as MF. Targeted therapies like flumatinib and rovadicitinib, as well as innovative immune-based approaches focused on CD47 may provide promising new options and overall treatment strategies for patients.  In addition, findings on hospital volume provide insight on the importance of hospital experience and centralizing care, to optimize outcomes and improve survival for AML patients.

Speaker Disclosure Information: Dr Dagan reported no relevant disclosures for this presentation.