ASH 2025: The Top 10 Takeaways for Hematologic Oncology Care

In a 30-year retrospective analysis on outcomes associated with intensive chemotherapy among patients with acute myeloid leukemia across 10 ECOG-ACRIN phase 2 or 3 trials from 1984 to 2019, patients who were Black experienced a 31.3% greater risk of disease recurrence or death and a 21.2% higher risk of death compared with White populations.

The 2025 American Society of Hematology (ASH) Annual Meeting and Exposition has come and gone. In its wake, promising data across several oral presentations, poster sessions, late-breaking abstracts, and other panels hold much potential for redefining therapeutic standards in hematologic malignancy management. Researchers shared critical updates in the fields of multiple myeloma, leukemia, lymphoma, and other blood cancers, highlighting novel therapeutic agents and strategies that may bolster outcomes for patients.

CancerNetwork® reported on the hottest findings to come out of this year’s meeting. Here are the top 10 articles from the 2025 ASH Meeting on data that may shift the hematologic oncology paradigm:

#1: Poorer Outcomes Observed for Black Patients Undergoing Chemotherapy for AML

In a 30-year retrospective analysis on outcomes associated with intensive chemotherapy among patients with acute myeloid leukemia (AML) across 10 ECOG-ACRIN phase 2 or 3 trials from 1984 to 2019, patients who were Black experienced a 31.3% greater risk of disease recurrence or death and a 21.2% higher risk of death compared with White populations.1 When comparing outcomes for Black vs White populations, the HR for overall survival (OS) was 1.212 (95% CI, 1.01-1.453; P = .0383), and the HR for disease-free survival (DFS) was 1.313 (95% CI, 1.05-1.641).

“There is a need for analysis of large representative AML data sets with integration of ancestry, social factors, and comprehensive genomic profiling of AML in order to elucidate the interaction between race and outcome disparities in AML,” study investigator Shella Saint Fleur-Lominy, MD, PhD, a physician at The University of Maryland School of Medicine’s Marlene and Stewart Greenebaum Comprehensive Cancer Center in Baltimore, Maryland, stated in her presentation of the data.

#2: Epcoritamab Combo Significantly Improves Efficacy in 2L R/R Follicular Lymphoma

Data from the phase 3 EPCORE FL-1 trial (NCT05409066) showed that a fixed-duration regimen of epcoritamab-bysp (Epkinly) plus rituximab (Rituxan) and lenalidomide (Revlimid; R2) significantly improved progression-free survival (PFS) and responses vs R2 alone among those with relapsed/refractory follicular lymphoma.2 In the epcoritamab plus R2 arm and R2 alone arm, respectively, the median PFS was not estimable (NE; 95% CI, NE-NE) vs 11.7 months (95% CI, 11.1-15.1; HR, 0.21; 95% CI, 0.14-0.31; P <.0001), and the objective response rates (ORRs) were 95% vs 79%.

According to presenting study investigator Lorenzo Falchi, MD, of the Lymphoma Service at Memorial Sloan Kettering Cancer Center in New York, NY, data from the EPCORE FL-1 trial set “a new benchmark” for the epcoritamab combination as “standard of care for second-line [and beyond] follicular lymphoma.”

In November 2025, the FDA approved epcoritamab plus R2 for patients with relapsed/refractory follicular lymphoma based on data from EPCORE FL-1.3

#3: Blinatumomab/Ponatinib Provides Chemo-Free Option in Ph+ ALL

A head-to-head comparison of findings in the phase 3 GIMEMA ALL2820 trial (NCT04722848) favored blinatumomab (Blincyto) plus ponatinib (Iclusig) vs imatinib (Gleevec) plus chemotherapy in the treatment of patients with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL).4 Of note, a complete hematologic response occurred in 94.3% of the blinatumomab arm vs 79.4% of the imatinib arm (P = .004).

These data support “a significant advantage of a chemotherapy-free, targeted immunotherapeutic-based approach over a tyrosine kinase inhibitor and chemotherapy strategy” in this ALL population, according to study investigator Sabina Chiaretti, MD, PhD, from the Sapienza University of Rome in Italy.

#4: Survival Benefit Seen With Cilta-Cel in Earlier Lines of Myeloma Treatment

In a correlative analysis, which included data from the phase 1b/2 CARTITUDE-1 (NCT03548207) and phase 3 CARTITUDE-4 (NCT04181827) trials, earlier intervention with ciltacabtagene autoleucel (cilta-cel; Carvykti) correlated with improved survival outcomes among patients with relapsed/refractory multiple myeloma.5 For example, patients with 1 prior line of treatment experienced the highest survival rates compared with those who received 2, 3, or 4 or more prior lines.

“Our data support treating patients with relapsed/refractory myeloma with cilta-cel in earlier lines of therapy,” according to presenting study investigator Samir Parekh, MBBS, professor of Medicine (Hematology and Medical Oncology) and Oncological Sciences at the Icahn School of Medicine at Mount Sinai.

#5: Talquetamab Combo Yields Responses in Multiple Myeloma With True EMD

Deep, durable responses were reported among patients with triple-class-exposed relapsed/refractory multiple myeloma and true extramedullary disease (EMD) who received talquetamab-tgvs (Talvey) in combination with teclistamab-cqyv (Tecvayli) as part of the phase 2 RedirecTT-1 trial (NCT04586426). This was noted by presenting study investigator Saad Z. Usmani, MD, MBA, FACP, FASCO, myeloma specialist and cellular therapist, and chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center.6

Data showed an ORR of 79% (95% CI, 69%-87%), a median time to first response of 2.6 months (range, 1.0-5.8), a median duration of response (DOR) that was not reached (NR; 95% 11.5-NE), and a 12-month DOR rate of 62.1% (95% CI, 49.0%-72.7%). Responses were typically higher among patients with lower baseline volumes of EMD, although responses among those with higher volumes were comparable to reports in the overall population.

#6: Real-World Elranatamab Maintains Responses in Elderly, Frail R/R Multiple Myeloma

One presentation showed that the real-world use of elranatamab-bcmm (Elrexfio) produced numerically shorter PFS but improved response rates vs teclistamab among patients with relapsed/refractory multiple myeloma.7 Of note, higher lactate dehydrogenase correlated with worse PFS (HR, 1.3) and OS (HR, 1.4), while prior exposure to BCMA-directed agents was associated with a lower complete response (CR) or better rate (adjusted OR, 0.32; P = .037).

“Despite its limitations, elranatamab is an important addition to our therapeutic armamentarium. Our data reinforce its effectiveness beyond the clinical trial population and highlight areas where supportive care may improve outcomes,” study investigator Andrew J. Portuguese, MD, an assistant professor in the Clinical Research Division and a physician at Fred Hutch, and an assistant professor in the Division of Hematology and Oncology at the University of Washington School of Medicine, noted in his presentation of the data.

#7: Linvoseltamab Yields High Response in Newly Diagnosed Multiple Myeloma

The use of linvoseltamab (Lynozyfic) generated high response rates among patients with newly diagnosed multiple myeloma enrolled on the phase 1/2 LINKER-MM4 trial (NCT05828511).8 Among 43 patients who were evaluable for response, 56% achieved a very good partial response (VGPR) or better, 26% had a CR or better, and 82% of those with a CR responded within 6 months of beginning treatment.

According to presenting study author Robert Orlowski, MD, PhD, chairman, ad interim, director of Myeloma, and professor of Medicine in the Departments of Lymphoma/Myeloma and Experimental Therapeutics of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, the data “support a positive benefit-to-risk profile” for linvoseltamab in this population.

#8: Azacitidine Plus Venetoclax Improves EFS in Acute Myeloid Leukemia

Combining venetoclax (Venclexta) with azacitidine (Vidaza) prolonged event-free survival (EFS) vs intensive induction chemotherapy among patients with AML in the phase 2 PARADIGM trial (NCT04801797).9 Findings revealed a median EFS of 14.6 months in the venetoclax arm and 6.2 months in the chemotherapy arm, with 1-year rates of 53% and 39% in each arm.

“[T]hese data support the use of azacitidine and venetoclax in functionally fit patients eligible for transplant with intermediate or adverse risk, FLT3 wild-type AML,” study investigator Amir Fathi, MD, program director of the Center for Leukemia at the Massachusetts General Hospital Cancer Center, concluded in his presentation on the trial.

#9: Fixed-Duration Venetoclax Combos Show Noninferior PFS to Ibrutinib in CLL

Compared with continuous single-agent ibrutinib, fixed-duration therapy with venetoclax plus obinutuzumab (Gazyva) or ibrutinib showed noninferior PFS outcomes among patients with previously untreated chronic lymphocytic leukemia (CLL) in the phase 3 CLL17 trial (NCT04608318).10 The HR was 0.87 (type-I-error adjusted 98.3% CI, 0.54-1.41) for venetoclax/obinutuzumab vs ibrutinib and 0.84 (type-I-error adjusted 98.0% CI, 0.53-1.32) for venetoclax/ibrutinib vs ibrutinib.

Data from this study affirm that “most patients with previously untreated CLL should be considered for a fixed-duration treatment” to enable treatment-free intervals, according to presenting study investigator Othman Al-Sawaf, MD, hematologist and medical oncologist in the Department of Hematology and Oncology of the University Hospital of Cologne in Cologne, Germany.

#10: Gintemetostat Has Single-Agent Activity in Pretreated R/R Multiple Myeloma

Preliminary single-agent activity with gintemetostat (KTX-1001) was reported among patients with heavily pretreated relapsed/refractory multiple myeloma in a phase 1 study (NCT05651932).11 Of note, investigators observed 1 VGPR, 1 PR, 2 minimal responses, and 12 instances of stable disease among 40 evaluable patients.

“In the dose-escalation phase, gintemetostat monotherapy showed a favorable safety and tolerability profile and demonstrated disease control and efficacy,” Saad Usmani stated in a presentation on these results.

References

1. Saint Fleur-Lominy S, Chen L, Sun Z, et al. Inferior survival in black AML patients treated with intensive chemotherapy in ECOG-ACRIN clinical trials is independent of cytogenetic profiles. Blood. 2025;146(suppl 1):290.
2. Falchi L, Nijland M, Huang H, et al. Primary phase 3 results from the EPCORE- FL-1 trial of epcoritamab with rituximab and lenalidomide (R2) versus R2 for relapsed or refractory follicular lymphoma. Blood. 2025;146(supplement 1):466. doi:10.1182/blood-2025-466
3. FDA approves epcoritamab-bysp for follicular lymphoma indications. News release. FDA. November 18, 2025. Accessed December 10, 2025. https://tinyurl.com/4utb74x3
4. Chiaretti S, Di Trani M, Skert C, et al. First results of the Phase III GIMEMA ALL2820 trial comparing ponatinib plus blinatumomab to imatinib and chemotherapy for newly diagnosed adult Ph+ acute lymphoblastic leukemia patients. Blood. 2025;146(suppl 1):439. doi.10.1182/blood-2025-439
5. Parekh S, Li K, van de Donk NWCJ, et al. Earlier use of ciltacabtagene autoleucel (cilta-cel) is associated with better immune fitness and stronger immune effects as shown by correlative analysis of peripheral blood and the bone marrow tumor microenvironment (TME) from the CARTITUDE-4 study. Blood. 2025;146(suppl 1):92. doi:10.1182/blood-2025-92
6. Usmani S, Kumar S, Mateos MV, et al. Efficacy and safety of talquetamab + teclistamab in patients with Relapsed/Refractory multiple myeloma and extramedullary disease: Updated Phase 2 results from the redirectt-1 study with extended follow-up. Blood. 2025;146(supp 1):698. doi:10.1182/blood-2025-698
7. Portuguese AJ, Davis J, Raza S, et al. Real-world outcomes with elranatamab in multiple myeloma: A multi-center analysis from the United States multiple myeloma immunotherapy consortium. Blood. 2025;146(supp_1):136. doi:10.1182/blood-2025-136
8. Orlowski R, Shah M, Chakraborty R, et al. Safety and efficacy of linvoseltamab as a simplified monotherapy first-line regimen in NDMM: Initial Results from the window of opportunity phase 1/2 LINKER-MM4 trial. Blood. 2025;146(suppl 1):697. doi:10.1182/blood-2025-697
9. 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. doi:10.1182/blood-2025-6
10. Al-Sawaf O, Stumpf J, Zhang C, et al. Fixed-duration versus continuous targeted treatment for previously untreated chronic lymphocytic leukemia: Results from the randomized CLL17 trial. Blood. 2025;146(supplement 1):1. doi:10.1182/blood-2025-1
11. Usmani S, Bories P, Gasparetto C, et al. Phase 1 study of ktx-1001, a first-in-class oral MMSET/NSD2 inhibitor, demonstrates clinical activity in relapsed/refractory multiple myeloma. Blood. 2025;146(suppl 1): 250. doi:10.1182/blood-2025-250