INDEPENDENCE, Type II JAK Inhibitor Data Highlight Key MPN and AML Data Arriving at EHA 2026

With the 2026 EHA Congress inching closer, attention is turned to the myeloproliferative neoplasm (MPN) field, where experts are expecting key data across different portions of clinical trials that could help refine clinical approaches and highlight novel agents coming down the pike.

To help preview some of the key MPN and acute myeloid leukemia (AML) data expected at EHA 2026, we gathered insights from:

• Aaron Gerds, MD, MS, a physician in the Department of Hematology and Medical Oncology at Cleveland Clinic, as well as an assistant professor in the Department of Medicine of the School of Medicine, deputy associate director for Clinical Research, and member of the Developmental Therapeutics Program at Case Comprehensive Cancer Center of Case Western Reserve University, in Ohio
• Anthony M. Hunter, MD, an associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine, medical director of the Immediate Care Center, and leader of the Myeloproliferative Neoplasm Program at Emory Winship Cancer Institute in Atlanta, Georgia
• Lore Gruenbaum, PhD, chief scientific officer and senior vice president of Research at Blood Cancer United

MPNs

Efficacy and safety of luspatercept in patients with myelofibrosis on Janus kinase inhibitors who require red blood cell transfusions: primary analysis of the phase 3 INDEPENDENCE trial

Gerds: If we think about the MPN landscape right now and the data that we're all eagerly awaiting...first and foremost, are the results of the [phase 3] INDEPDENCE study [NCT04717414]. The INDEPENDENCE trial is a prospective, randomized phase 3 trial looking at luspatercept [Reblozyl], a drug that's designed to support anemia when it's related to myelofibrosis vs placebo. Now, there was a press release that came out nearly a year ago, noting that [the study] missed its primary end point, and through lots of discussions, we know that it missed its primary end point by a very slim margin. It hit a lot of key secondary end points, but the idea of this trial was that it was going to [support potential] label expansion for luspatercept.

Luspatercept is already FDA approved to treat anemia as a result of myelodysplastic syndromes and beta thalassemia, but this would be a huge win for the myelofibrosis field, because anemia is incredibly common, it's prognostic, it's difficult to treat, and having a label indication would be helpful in order to gain access to this medication for patients. It's already in the [National Comprehensive Cancer Network] Guidelines, we use it off-label, but a label indication goes a long way again to increasing access for patients. Hearing that this phase 3 trial was negative was certainly a blow, but getting the data in hand, looking at the subsets, and looking at why the trial potentially fell short [will be important]. Is it more of trial design, is it efficacy? We really want to understand a little bit more detail on how this drug can be beneficial for patients. This is going to be hugely important because even if it doesn't get a label expansion, we still use [luspatercept] off-label quite regularly for patients, and our clinical sense is that it's still a valuable therapy. We're all eagerly awaiting these results, particularly because there was a fair amount of rumble in the field when the press release came out again a year ago, noting that it was negative for his primary end point, but by a slim margin. We want the details, we want to understand if this failed because of us. Did this fail because we had poor trial design and patient selection? Or is this more of an issue where we need to learn more on how well this drug can work in certain populations? That's a huge one that we're waiting for and hope to see this abstract season.

Hunter: It will be nice to see—for the first time presented—the initial data from the phase 3 INDEPENDENCE study. [We saw] the initial press release for it [that showed the study] did not quite meet its primary end point statistically, but we look forward to digging into more of the data there. It's an important one for us.

Results of AJX-101, a phase 1 clinical trial of the type II JAK2 inhibitor AJ1-11095, in patients with myelofibrosis who have been failed by a type I JAK2 inhibitor

Hunter: An interesting one and really some of the first data we've seen for a type II JAK inhibitor from the phase 1 AJX-101 trial [NCT06343805]. [We'll see] phase 1 data there that John Mascarenhas, MD, [of Mount Sinai,] will be presenting. [That's some potential] key information that we'll see for a first-in-class drug, and we'll see some initial data for it here.

Gerds: Another big thing is going to be the results from the phase 1 trial for the Ajax Therapeutics type II JAK inhibitor [AJ1-11095]. Why are we interested in this? Well, this is a type II JAK inhibitor. The other four JAK inhibitors that are FDA approved to treat myelofibrosis are type I JAK numbers, meaning they inhibit the active form of wild-type JAK2. Now, this is a type II JAK inhibitor, meaning it inhibits the inactive form of that molecule. There's a whole question of potency, if we can inhibit the inactivated version, can we really dial in that potency to a much greater degree relative to the toxicity profile of the drug? That's really where this is going, and we've been eagerly awaiting even just a glimpse of how well [type II JAK inhibitors] are going to work. There are concerns that it might work, but is it going to be overly myelosuppressive? Where is that line going to fall between efficacy and toxicity? However, with all this anticipation over the last couple of years, waiting for some results from the phase 1 trial—it will be scant because it's phase 1, [likely a small number of] patients, but there was a big fanfare in the field because Ajax [was acquired] by a larger pharmaceutical company, and that says in our mind that maybe the data that hasn't been yet presented are quite impressive. [The acquisition] heightened the anticipation, not that it wasn't already high, but it certainly augmented our excitement for seeing these results. We are excited to see those results being put forth to the public for review.

Mutant calreticulin–specific monoclonal antibody, INCA033989, is well tolerated and achieves robust spleen, anemia, and molecular responses in patients (pts) with myelofibrosis (MF)

Hunter: We've seen a couple recent meetings with some of the initial data from the CALR-directed monoclonal antibodies. Claire Harrison, MD, [of Guy's and St. Thomas at NHS,] will be presenting some of the myelofibrosis data there. That is another study we really look forward to see some more key data on.

Gerds: We're going to want to see more results from the monoclonal antibody study for [INCA033989]. The trial is ongoing, and we're unlikely to see huge swings in efficacy or toxicity as this trial continues to enroll patients. We're looking forward to the phase 3 trial with this drug. We kind of know what to expect from the monoclonal antibody at this point within the context of that phase 1 trials that are ongoing.

AML

Ziftomenib combined with intensive induction (7+3) for newly diagnosed NPM1‑m or KMT2A-r acute myeloid leukemia (AML): long-term results from the KOMET-007 trial

Gruenbaum: One [ongoing] theme in the AML world is menin inhibitors, and we'll get an update on one of those studies, with [long-term data from] the phase 1 KOMET-007 trial [NCT05735184]. This is a phase one trial with ziftomenib [Komzifti] and intensive induction therapy in the NPM1-mutated and KMT2A-rearranged AML setting. What we're all watching in this space is how quickly can these menin inhibitors, as novel agents, move into frontline [care]. Do we see not just higher response rates, but do we also see improved survival? Then there are other combinations [and approaches] that are of interest [with menin inhibitors], such as a menin inhibitors after transplant for maintenance. We have these early approvals for these agents. But, how do we use them best? Where is the best space and for which patients?

Reference

1. Bristol Myers Squibb announces topline results from phase 3 INDEPENDENCE trial for Reblozyl (luspatercept-aamt) in adult patients with myelofibrosis-associated anemia. News release. Bristol Myers Squibb. July 18, 2025. Accessed June 5, 2025. https://news.bms.com/news/details/2025/Bristol-Myers-Squibb-Announces-Topline-Results-from-Phase-3-INDEPENDENCE-Trial-for-Reblozyl-luspatercept-aamt-in-Adult-Patients-with-Myelofibrosis-Associated-Anemia/default.aspx