Highlights From the 2025 American Society of Hematology (ASH) Annual Meeting

Amir Ali, PharmD, BCOP - Clinical Oncology Pharmacist, University of Southern California, Los Angeles, CA

The 67th Annual Meeting of the American Society of Hematology (​​ASH) took place in Orlando, Florida, from December 6-9, 2025. The conference featured several impactful studies with direct implications for hematology pharmacy practice. Advances presented in 2025 spanned cellular therapy toxicity management, multiple myeloma regimens, and evolving frontline strategies across hematologic malignancies.

I was able to attend the conference in person and have summarized selected abstracts of high relevance to oncology/hematology pharmacists ​​below.

Dexamethasone for Management of Cytokine Release Syndrome Associated with Talquetamab¹

A wonderful group of oncology pharmacists worked on ​a ​multicenter abstract evaluating the use of dexamethasone as first-line management for low-grade cytokine release syndrome (CRS) in patients receiving talquetamab, a GPRC5D-directed bispecific antibody approved for relapsed/refractory multiple ​​​​myeloma. This retrospective analysis was conducted by a multidisciplinary group​,​ including clinical pharmacists​,​ and assessed safety outcomes, escalation of care, and need for tocilizumab.

Most CRS events occurred during step-up dosing and were grade 1–2 in severity. Administration of dexamethasone resulted in symptom ​resolution ​in the majority of patients, with limited need for tocilizumab and no increase in intensive care unit admissions or permanent treatment discontinuation. Importantly, early steroid use did not appear to compromise treatment response or ​​durability. Best ORR was similar (86% vs 90%, p=0.74) between dexamethasone and tocilizumab groups and the overall population of 77%

These findings suggest that dexamethasone may be a reasonable initial strategy for selected patients with low-grade CRS receiving ​​talquetamab. Pharmacists can play a critical role in implementing this approach by recommending dexamethasone over tocilizumab based on availability and cost.

Azacitidine Plus Venetoclax Versus Intensive Chemotherapy in Newly Diagnosed ​​AML²

The PARADIGM trial, a randomized study presented at ASH 2025​,​ compared azacitidine plus venetoclax with standard intensive induction chemotherapy in fit adults with newly diagnosed acute myeloid leukemia (AML).

In the trial, adults with newly diagnosed, untreated, transplant-eligible AML who were fit for intensive therapy were randomized to azacitidine plus venetoclax versus standard intensive chemotherapy, excluding patients with core binding factor AML, FLT3 mutations, and most NPM1-mutated disease. Azacitidine plus venetoclax significantly improved event-free survival (median 14.5 vs 6.2 months) and response rates, enabled more patients to proceed to transplant, and was associated with fewer severe infections, bleeding events, and hospitalizations, while overall survival was numerically, but not statistically, longer than with intensive chemotherapy.

From a pharmacy perspective, these findings support continued expansion of azacitidine plus venetoclax into frontline AML treatment. Key considerations include tumor lysis syndrome prevention, antifungal and antibacterial prophylaxis, venetoclax dose adjustments with CYP3A inhibitors, and management of prolonged cytopenias.

Fixed-Duration Venetoclax-Based Therapy Versus Continuous BTK Inhibition in CLL (CLL17 ​​Trial)³

The CLL17 trial compared fixed-duration venetoclax-based therapy with continuous BTK inhibitor treatment in patients with previously untreated chronic lymphocytic leukemia (CLL). At a median follow-up of 34.2 months, 3-year PFS was 81.1% with venetoclax–obinutuzumab, 79.4% with venetoclax–ibrutinib, and 81.0% with continuous ibrutinib, meeting noninferiority criteria (HRs 0.87 and 0.84 vs ibrutinib), while 3-year overall survival was 91.5%, 96.0%, and 95.7% respectively; fixed-duration arms also had higher complete response and MRD-negative rates, supporting fixed-duration venetoclax-based therapy as an effective alternative to continuous ibrutinib in previously untreated CLL. Fixed-duration regimens achieved deep and durable remissions, including high rates of undetectable minimal residual disease.

​​​These results highlight the importance of pharmacist involvement in tumor lysis risk stratification, laboratory monitoring during venetoclax ramp-up, and patient counseling regarding treatment timelines and adherence.

Venetoclax Plus Hypomethylating Agents in High-Risk MDS and MPN Blast Phase​​⁴

Several abstracts at ASH 2025 evaluated venetoclax in combination with hypomethylating agents in patients with high-risk myelodysplastic syndromes (MDS) and myeloproliferative neoplasm– blast phase (MPN-BP).

In this phase II study, patients were treated with venetoclax plus decitabine, with inclusion based on confirmed MPN-BP and typical exclusions for uncontrolled infection or organ dysfunction. The combination showed clinically meaningful activity in this very high-risk population, achieving notable response rates with manageable toxicity, supporting venetoclax plus hypomethylating therapy as a reasonable treatment option for patients with MPN-BP who are often elderly and have limited therapeutic alternatives. Response rates were clinically meaningful in select populations, with some patients successfully bridged to allogeneic stem cell transplantation.

Pharmacists should be prepared to manage prolonged myelosuppression, transfusion requirements, and infection risk associated with these regimens, particularly in heavily pretreated or older patients.

Teclistamab Plus Daratumumab Versus Standard Triplets in Relapsed/Refractory Multiple Myeloma⁵

A late-breaking abstract presented at ASH 2025 reported results from a phase 3 randomized study of teclistamab plus daratumumab compared with standard-of-care triplet regimens [daratumumab–pomalidomide–dexamethasone (DPd) or daratumumab–bortezomib–dexamethasone(DVd)] in patients with relapsed/refractory multiple myeloma. The teclistamab-based regimen demonstrated best-in-class efficacy outcomes, with superior depth and durability of response compared with both DPd and DVd. The median follow-up was 34.5 months, and the median progression free survival (PFS) for Tec-Dara had not been reached vs 18.1 months in DPd/DVd. The 36-month PFS rates were higher in Tec-Dara than comparator arm, 83.4% vs 29.7%, respectively, and the overall survival (OS) rate was 83.3% vs 65.0%.

Notably, this regimen received a National Priority Review Voucher from the U.S. Food and Drug Administration, and regulatory review is anticipated in the near term. After completion of step-up dosing and initial cycles, teclistamab was administered as subcutaneous monthly dosing after cycle 6, offering a convenient long-term treatment ​​strategy.

This combination represents an off-the-shelf alternative to BCMA-directed CAR T-cell therapy, potentially expanding access to highly effective cellular therapy for patients who are not candidates for CAR-T cellular therapy or who require rapid treatment initiation. As with other BCMA-targeted therapies, infection risk remains a key concern, underscoring the importance of pharmacist-led strategies for antimicrobial prophylaxis, immunoglobulin replacement, vaccination review, and early infection recognition.

Conclusion

ASH 2025 reinforced the expanding role of pharmacists in hematologic malignancies, particularly in optimizing toxicity management for cellular therapies and supporting broader use of venetoclax-containing regimens. As these therapies continue to move earlier in treatment paradigms, pharmacist leadership in protocol development, safety monitoring, and interdisciplinary education remains essential.

References

1.Dexamethasone for management of cytokine release syndrome associated with talquetamab in patients with relapsed/refractory multiple myeloma. Blood. 2025;146(Suppl 1):720. Presented at the American Society of Hematology Annual Meeting; December 2025; San Diego, CA.

2.Azacitidine plus venetoclax versus intensive chemotherapy in fit patients with newly diagnosed acute myeloid leukemia. Presented at the American Society of Hematology Annual Meeting; December 2025; San Diego, CA.

3.CLL17: Fixed-duration venetoclax-based therapy versus continuous BTK inhibition in treatment-naïve chronic lymphocytic leukemia. Presented at the American Society of Hematology Annual Meeting; December 2025; San Diego, CA.

4.Venetoclax plus hypomethylating agents in high-risk myelodysplastic syndromes and myeloproliferative neoplasm–blast phase. Presented at the American Society of Hematology Annual Meeting; December 2025; San Diego, CA.

5.Phase 3 randomized study of teclistamab plus daratumumab versus standard-of-care regimens in relapsed/refractory multiple myeloma. Blood. 2025;146(Suppl 2): LBA-6. Presented at the American Society of Hematology Annual Meeting; December 2025; San Diego, CA.