Experts Spotlight ASH 2025 Data Poised to Change Treatment Paradigms in AML, MZL, and Myeloma

Among the myriad of data presented during the 2025 ASH Annual Meeting and Exposition, several studies signaled a clear departure from long-standing treatment norms, according to experts. These presentations underscored meaningful shifts in the management of several hematologic malignancies, particularly with respect to the role of low-intensity regimens in acute myeloid leukemia (AML), expanded applications for CAR T-cell therapy in marginal zone lymphoma (MZL), and the potential for bispecific antibodies to redefine standards of care in multiple myeloma in both the relapsed/refractory and frontline settings.

During the meeting, OncLive® invited the following experts to identify the most practice-changing or -informing studies presented in their respective fields:

• David J. Andorsky, MD,a medical oncologist/hematologist at Rocky Mountain Cancer Centers in Englewood, Colorado, and an associate chair for US Oncology Hematology Research.
• Wei Ying Jen, MA (Oxon), BM BCh, M Med (Internal Medicine), MRCP (UK), FRCPath (UK, Haematology), an assistant professor in the Department of Leukemia, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston.
• Hannah Goulart, MD, a hematology oncology fellow at The University of Texas MD Anderson Cancer Center.
• Manali Kamdar, MD, an associate professor of medicine-hematology in the Division of Hematology at the University of Colorado and clinical director of Lymphoma Services at the UCHealth Blood Disorders and Cell Therapies Center—Anschutz Medical Campus and the University of Colorado Cancer Center in Aurora.
• Sankalp Arora, MBBS, a hematology oncology fellow at The University of Texas MD Anderson Cancer Center.
• Noa Biran, MD, an associate professor of medicine at Hackensack University School of Medicine and hematologist/oncologist in the Multiple Myeloma Division at John Theurer Cancer Center in New Jersey.
• Claudio Cerchione, MD, PhD an adjunct professor in the Department of Pharmacy and Biotechnology and Department of Pharmacy and Biotechnology at the University of Bologna in Italy.

Read on for their perspectives on why these studies are poised to influence practice.

Do data from the phase 2 PARADIGM study (NCT04801797) signal a change in the management of newly diagnosed AML?

Andorsky: The PARADIGM study evaluated venetoclax [Venclexta] and azacitidine vs more intensive chemotherapy. [Findings presented at ASH] suggested that for many patients, venetoclax plus azacitidine, which is the better tolerated therapy, may [also be more beneficial]. Those are 2 things that a lot of us have suspected in the field and have been hoping to see, so having [randomized] data demonstrating both those findings is really exciting, and is probably going to change practice going forward.

Jen: [This presentation shows that] it might be possible to use azacitidine and venetoclax outside of its [current indication for patients] older than 75 years. We do know that the median age of the patients who were enrolled in that study was still a bit older. It will be interesting to see how [these data] will inform our practice moving forward.

Arora: The PARADIGM trial is everywhere right now across all outlets, and obviously so; it represents a big change in the treatment [paradigm for AML]. Historically, we've always said that fit patients get 7+3 [chemotherapy], while older, unfit patients get hypomethylating agents [HMAs] and venetoclax. The PARADIGM trial clearly showed that for certain subtypes of AML, using HMAs/venetoclax, even in fit, newly diagnosed patients, actually leads to better outcomes. Clearly has the potential to change practice.

There are caveats. We have to focus on the inclusion criteria, as [the trial] excluded patients with TP53 mutations, NPM1 mutations, and core-binding factor AML. We have to make sure that the message we send out to the community is not that HMA/venetoclax [should now be used] for all fit patients with AML. However, with these important caveats in mind, this is a practice-changing study [showing] that HMA/venetoclax could be a useful option in fit patients with certain types of AML.

Goulart: This could potentially be paradigm-shifting for many patients who traditionally would have received intensive chemotherapy. After hearing the results of this study, there may be a shift towards more HMA-based regimens for these patients, especially if we can get them to transplant safely and without increased toxicity.

What findings from the phase 2 TRANSCEND FL trial (NCT042458839) support the recent FDA approval of lisocabtagene maraleucel (liso-cel; Breyanzi) for MZL?

Kamdar: Some of the data that [were presented] with liso-cel in MZL and in follicular lymphoma are very impressive. Long-term data were presented [after] 3 years of follow-up in the TRANSCEND FL trial with liso-cel, and the benefit that it is showing in patients with high tumor burden and early progressing disease is just spectacular. The patient-reported outcome data in patients who receive liso-cel in the MZL cohort [was also of interest].

[On December 4, 2025], the FDA approved liso-cel for relapsed/refractory MZL in the third-line setting. There's something now that patients can get for this lymphoma that is rare, but is very frequently relapsing. We need better outcomes there.

Should teclistamab-cqvy (Tecvayli) be considered a new standard of care in relapsed/refractory multiple myeloma based on data from the phase 3 MajesTEC-3 trial (NCT05083169)?

Cerchione: The most interesting data in relapsed/refractory multiple myeloma come from the phase 3 MajesTEC-3 trial, in which teclistamab, an anti-BCMA/anti-CD3[–directed] bispecific antibody has been combined with daratumumab [Darzalex] vs standard-of-care daratumumab plus dexamethasone and either pomalidomide [Pomalyst; DPd] or bortezomib [Velcade; DVd]. Those [data are] incredible in terms of the depth of response and progression-free survival. However, the most impressive [finding from this study] is that we can spare dexamethasone. It is used only in the first part of the treatment, so this correlates with the quality of life and also tolerability of our patients.

The regimen can be toxic in the first part of the treatment, in which we see a high rate of infections. However, this study was initiated in 2021 when we were not able to manage these [related toxicities] with adequate supplements of immunoglobulin and adequate prophylaxis with antibiotics and antivirals, [as per] the recommendations that we have today. If we repeat the treatment today, something should change in order to improve tolerability. However, this regimen could be considered a potential new SOC starting from early relapse, as [it has shown] a high [36-month OS rate]. Other data are needed to confirm this [benefit].

Do early data with linvoseltamab-gcpt (Lynozyfic) indicate a shift away from traditional lenalidomide (Revlimid) maintenance in first-line multiple myeloma?

Cerchione: Novel [regimens] are also arriving in frontline therapy, such as linvoseltamab, a newer-generation anti-BCMA/anti-CD3[–directed] bispecific antibody.In the phase 1/2 LINKER-MM4 trial [NCT05828511], linvoseltamab is being evaluated as monotherapy in both transplant-eligible and -ineligible patients [with newly diagnosed multiple myeloma], and continued to show high response rates.

Biran: We're seeing renewed focus on the post-transplant setting where we can really alter the natural course of the disease. One study that looked the BCMA T-cell engager linvoseltamab in the post-transplant consolidation setting was [the phase 1b LINKER-MM2 trial (NCT05137054).] [Data from this study] showed that 6 months of therapy with linvoseltamab achieved nearly a 100% minimal residual disease negativity rate in these patients. That's going to be a game-changer and lead to many more studies looking at immune therapy and T-cell engagers and even other trispecific antibodies in this setting.