Dr Richard Stone Weighs the Future of 7+3 in AML Treatment

For decades, the “7+3” strategy—comprising 7 days of continuous infusion cytarabine combined with 3 days of an anthracycline such as daunorubicin—has served as the backbone of intensive induction therapy for newly diagnosed acute myeloid leukemia (AML), rapidly inducing remission in patients.¹ Although historically administered as a standalone regimen, the 7+3 backbone is increasingly being combined with other agents based on a patient’s specific disease characteristics. In some cases, it is also being substituted altogether in favor of a less intensive regimen.

At the Baptist Health Miami Cancer Institute’s 7^th Annual Immunotherapies Summit for Hematologic Malignancies, Richard Stone, MD, of Dana-Farber Cancer Institute and Harvard Medical School, examined where 7+3 currently stands in the evolving AML treatment paradigm. His presentation placed the regimen in the context of emerging data evaluating newer combinations and lower-intensity therapeutic strategies.

In an interview with Targeted Oncology ahead of the meeting, Stone outlined key considerations surrounding the ongoing debate about whether 7+3 should remain the standard approach for patients with AML as treatment options continue to expand.

Targeted Oncology: Could you provide a brief overview of your upcoming talk?

Richard Stone, MD: The topic of my talk is, “Is 7+3 still the standard of care in AML?” That's still very much an open question in today's therapeutic landscape. One issue that came up that is on everybody's mind is whether it might be possible to substitute a less intensive therapy for 7+3 and get the same results. That's based on the success of a regimen called azacitidine [Vidaza] and venetoclax [Venclexta] in older adults with AML, and there [have] been some uncontrolled data in younger adults with AML [indicating] that it might be useful. And now there's finally a presentation of data from a randomized, prospective phase 2 trial [PARADIGM; NCT04801797] comparing 7+3 [with] azacitidine and venetoclax in previously untreated adults with AML who do not have favorable-risk disease.

[These] data [were] presented by Dr Amir Fathi, a colleague of mine from Boston, at the plenary session of the American Society of Hematology meeting in December of 2025. That study seemed to show that those who were randomized to azacitidine and venetoclax enjoyed a superior event-free survival than those who were randomized to 7+3.² The overall survival data seem to be equivalent in the 2 arms. So, the study brings up some interesting questions about the utility of 7+3.

I should say that…the toxicity of the azacitidine and venetoclax regimen was clearly less than the toxicity of the 7+3 regimen, but there are still some outstanding issues. We haven't seen the full data. We haven't seen much data according to subgroups, and so it still remains to be seen what the long-term outcome will be. But my talk will discuss that trial and also discuss other subgroups of AML who are clearly still treated with 7+3 or similar, along with adjunctive agents such as gemtuzumab ozogamicin [Mylotarg] or FLT3 inhibitors.

What factors determine whether a patient is still a good candidate for intensive induction therapy with the 7+3 regimen?

It's a combination of host and disease factors. When I say host factors, I mean, can the patient tolerate 7+3 based on their age and comorbid disease? If the answer is yes, then it's an open question about whether they should get it. Then we devolve into discussing whether they should get it based on disease factors, namely cytogenetic and genetic analysis, which leads to different subgroups that might benefit from a specific targeted therapy, or whether their risk justifies using intensive chemotherapy or not.

In the near future, do you think we’ll still be asking the same question—whether 7+3 is the standard—as more less-intensive and targeted treatment strategies emerge?

[Currently,] I would say it's a minority, maybe a sizable minority, of patients who receive 7+3 alone, or something similar to that alone. Many are getting FLT3 inhibitors or gemtuzumab. Others are getting substitution of liposomal encapsulated daunorubicin and cytarabine or CPX351, so there's very few that are getting 7+3 alone. And in the future, I think they'll be even fewer. Maybe no one will get 7+3 alone anymore. They'll get 7+3 plus something if they have chemo-responsive disease; maybe that'll be venetoclax. And many patients will get azacitidine or another hypomethylating agent like decitabine plus venetoclax, with or without additional therapies as well.

For example, in the FLT3 field, people might be getting only nonintensive therapy, maybe only all-oral therapy. I can see a day where a patient with a FLT3 mutation might receive a hypomethylating agent, venetoclax, and a FLT3 inhibitor. And that might be enough to get them into remission and maybe go right to a stem cell transplant, or possibly even obviate the need for stem cell transplant. I'm optimistic that we'll be able to subject patients to less toxic therapy in the future, in the vast majority of cases.

Which of these emerging treatment strategies are you particularly excited about?

Using FLT3 inhibitors plus either high-dose or low-dose chemotherapy is almost passe right now. The new kid on the block is clearly menin inhibitors, which have been approved already as single agents in relapsed/refractory disease. The subtypes in which they've been approved are KMT2A rearrangement disease, which is fairly unusual in older adults, more common in pediatric patients; and NPM1-mutant disease, which is not unusual in adults, although it's chemo-responsive—sometimes patients relapse and/or need help. My guess is that menin inhibitors will be used along with either intensive or nonintensive chemotherapy routinely in the upfront setting to treat patients with one of those 2 genetic lesions, and maybe even other genetic lesions too.

REFERENCES

1. Rowe JM. The "7+3" regimen in acute myeloid leukemia. Haematologica. 2022;107(1):3. Published 2022 Jan 1. doi:10.3324/haematol.2021.280161

2. 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(Supplement 1):6-6. doi: 10.1182/blood-2025-6