In this episode, we dive deep into ASH 2025 updates on myeloid malignancies with Dr. Curtis Lachowiez. From the plenary halls of ASH 2025 to long-term follow-up of Aza/Ven/Gilteritinib, we unpack what the latest evidence means for the future of AML management.

1. PARADIGM Trial (Plenary Session, Abstract 6)

Fathi A, Perl A, Fell G, et al. Results from PARADIGM – a phase 2 randomized multi-center study comparing azacitidine and venetoclax to conventional induction chemotherapy for newly diagnosed fit adults with acute myeloid leukemia. Blood 2025;146(Suppl 1):6.

https://doi.org/10.1182/blood-2025-6

ClinicalTrials.gov: NCT04801797

2. VICEROY Study – Aza/Ven/Gilteritinib Triplet (Abstract 654)

Venetoclax (VEN) and azacitidine (AZA) with gilteritinib (GILT) in patients with newly diagnosed FLT3mut+ AML ineligible for intensive induction chemotherapy: Interim results from the phase 1/2 VICEROY study. Blood 2025;146(Suppl 1):654.

ClinicalTrials.gov: NCT05520567

3. Long-Term Follow-Up of Aza/Ven/Gilteritinib in FLT3-Mutated AML (Abstract 45)

Azevedo RS, et al. Long-term follow-up of azacitidine, venetoclax, and gilteritinib in patients with newly diagnosed FLT3-mutated acute myeloid leukemia. Blood 2025;146(Suppl 1):45.

Original publication: Short NJ, Daver N, DiNardo CD, et al. J Clin Oncol 2024;42:1499–1508. https://doi.org/10.1200/JCO.23.01911

ClinicalTrials.gov: NCT04140487

4. PRISM-AML Score (Abstract 453)

Lachowiez CA, et al. Prognostic risk integration for survival modeling (PRISM) in newly diagnosed acute myeloid leukemia treated with venetoclax: A multinational retrospective cohort study. Blood 2025;146(Suppl 1):453.

Interactive Calculator: https://prism-aml.com

5. Additional Studies Referenced in Discussion

• VIALE-A Trial: DiNardo CD, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med 2020;383:617–629. (NCT02993523)

• VERONA Trial: Randomized study of Aza-Ven vs. Aza vs. placebo in MDS (discussed as a negative study)

• 4-Gene Classifier (mPRS): Bataller A, et al. Prognostic risk signature in patients with AML treated with HMA and venetoclax. Blood Adv 2024;8(4):927–935. https://doi.org/10.1182/bloodadvances.2023011757

• LACEWING Trial: Azacitidine plus gilteritinib vs. azacitidine plus placebo in FLT3-mutated AML (discussed as a negative study)

BloodCancerTalks: ASH 2025 Lymphoma Roundup

Guest: Dr. Carla Casulo, Associate Professor, Wilmot Cancer Centre, University of Rochester

Abstracts Discussed

Follicular Lymphoma

EPCORE-FL1 (Falchi) - Epcoritamab plus lenalidomide-rituximab (R2) in relapsed/refractory FL

Theme: Bispecific antibody combinations in R/R FL; comparing to other approaches

Diffuse Large B-Cell Lymphoma (DLBCL) - Elderly/Unfit Patients

MorningSun (Sharman) - Mosunetuzumab monotherapy in patients ≥80 years or chemo-ineligible

EPCOR-DLBCL-3 (Vitolo) - Epcoritamab monotherapy in elderly patients

R-Pola-Glo - Rituximab-polatuzumab-glofitamab combination in older/frail patients

Theme: Single-agent and combination bispecific strategies for elderly and frail DLBCL patients

DLBCL - First-Line Treatment

SMART STOP (Westin) - Chemotherapy-free approach using lenalidomide, tafasitamab, rituximab, acalabrutinib (ULTRA regimen)

FrontMIND - Tafasitamab-lenalidomide added to R-CHOP

Theme: Chemotherapy-sparing and chemo-intensification strategies in newly diagnosed DLBCL

DLBCL - Relapsed/Refractory

DALY 2-EU (Borchmann) - Dual CD19/CD20 CAR-T (zamto-cel) versus R-GemOx in transplant-ineligible patients

Theme: Expanding CAR-T eligibility; treatment selection in transplant-ineligible R/R DLBCL

Hodgkin Lymphoma

SWOG 1826 - 3-year update: Nivolumab-AVD versus brentuximab-AVD

HD21 - 5-year update: PET-adapted BrECADD versus BEACOPP

Theme: Long-term outcomes and treatment selection in newly diagnosed Hodgkin lymphoma

Burkitt Lymphoma

ZUMA-25 (Van Dorp) - Brexucabtagene autoleucel (Brexu-cel) in relapsed/refractory Burkitt

Theme: CAR-T therapy for the challenging population of R/R Burkitt lymphoma

Mantle Cell Lymphoma - First-Line

TrAVeRse - Acalabrutinib, venetoclax, rituximab

GLOVe - Glofitamab, lenalidomide, venetoclax (high-risk MCL)

BOVen - Zanubrutinib, obinutuzumab, venetoclax (older patients)

MAVO - Acalabrutinib, venetoclax, obinutuzumab

Window-3 - Acalabrutinib-rituximab followed by brexu-cel (high-risk MCL)

Theme: Chemotherapy-free combinations in newly diagnosed mantle cell lymphoma

Join hosts Raj, Ashwin, and Eddie in this episode of Blood Cancer Talks as they welcome Dr. Luciano Costa, the first author of the NEJM manuscript on the MajesTEC-3 RCT, which was presented at ASH 2025. This episode dives deep into the trial's topline findings, capturing the nuances of the patient population, efficacy and safety data, and the future implications for treatment. The episode also examines the comparative efficacy of bispecific T-cell engagers versus CAR-T therapies, along with spirited discussion on the potential for fixed-duration treatment in myeloma care.

Episode Highlights

Main Topics Covered

1. MajesTEC-3 Trial: Teclistamab-Daratumumab vs. Standard of Care
   • Trial design and patient population
   • Primary endpoint: Progression-free survival (PFS)
   • MRD negativity rates and depth of response
   • Overall survival and safety profile
   • Clinical implications for treatment selection
2. Treatment Selection in Early Relapse
   • Comparing MajesTEC-3 and CARTITUDE-4 patient populations
   • Framework for choosing between bispecific antibodies vs. CAR T-cell therapy
   • Managing anti-CD38 exposed patients

Link to the NEJM paper: https://www.nejm.org/doi/abs/10.1056/NEJMoa2514663