Key Leukemia and Myelofibrosis Presentations at EHA 2026

EHA 2026 Leukemia and Myelofibrosis Presentations

Eunice Wang, MD, of Roswell Park Comprehensive Cancer Center, joined Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, on the Oncology Brothers podcast to discuss three key presentations from the 31st European Hematology Association Annual Congress (EHA 2026). Together, the doctors reviewed data from the OPTI-AML and KOMET-007 trials in leukemia, and the SENTRY trial in myelofibrosis. 

OPTI-AML: Reduced Duration Schedule for Azacitidine-Venetoclax in AML

The prospective randomized phase 2 OPTI-AML trial compared a 14-day schedule of azacitidine and venetoclax with the conventional 28-day schedule in patients aged 60 years or higher with newly diagnosed AML. Patients were randomized to receive azacitidine on days 1 to 7 plus venetoclax on either days 1 to 28 (AV28) or 1 to 14 (AV14) for 2 cycles. Complete remission (CR) was assessed on days 21 to 28 of each cycle, and the primary end point was CR rate across both cycles for each group. 

After 2 cycles, the overall CR rate was 49% in the AV28 arm and 43% in the AV14 arm (95% CI, -8% to 21%). The CR rate after cycle 1 was 26% for both arms. Patients with NPM1 and IDH1/2 mutations showed higher CR rates with AV28 (61% vs 42%), but CR rates were comparable between arms (44%) for remaining molecular subgroups. The CR, CR with partial hematologic recovery, or CR with incomplete count recovery composite (CRc) rate was 81% with AV28 and 69% with AV14. Minimal residual disease (MRD) clearance and toxicity outcomes were comparable between arms. 

While the study’s small sample size and short intervention duration limit interpretation and long-term conclusions, the data may support AV14 as an option for patients with AML as long as they do not carry NPM1 or IDH1/2 mutations, said Dr. Wang.

KOMET-007: Combining Ziftomenib With Standard Chemotherapy for AML

Ziftomenib is a selective oral menin inhibitor approved as monotherapy for patients with relapsed or refractory NPM1–mutated AML. The phase 1a/b KOMET-007 trial evaluated ziftomenib plus standard intensive 7+3 induction chemotherapy for patients with NPM1–mutated or KMT2A–rearranged AML. 

At the time of presentation, the median follow-up was 14.9 months for NPM1–mutated patients and 9.3 months for KMT2A–rearranged patients. The most common grade 3 or higher treatment-emergent adverse events (AEs) were febrile neutropenia (64%), thrombocytopenia (57%), anemia (36%), neutropenia (28%), and leukopenia (27%), with comparable rates between the two subgroups. Ziftomenib–related grade 3 or higher AEs occurred in 54% of patients, most commonly thrombocytopenia (21%), anemia (15%), neutropenia (13%), febrile neutropenia (13%), and pruritus (10%). Grade 3 differentiation syndrome related to ziftomenib occurred in 3 KMT2A–rearranged patients. Grade 3 QTc prolongation occurred in 1 NPM1–mutated and 3 KMT2A–rearranged patients, with 1 case deemed ziftomenib–related.

The CRc rates were 96% for NPM1–mutated patients and 90% for KMT2A–rearranged patients, with respective local MRD negativity rates of 83% and 82%. Median CRc duration was not reached for NPM1–mutated patients and 11.2 months for KMT2A–rearranged patients. Median overall survival (OS) was not reached for either group with 1-year OS rates of 94% and 70% for NPM1–mutated and KMT2A–rearranged patients, respectively. 

Overall, the data suggest ziftomenib is an “extremely promising and well tolerated addition to intensive chemotherapy” for fit patients with NPM1–mutated or KMT2A–rearranged AML, said Dr. Wang. Moving forward, the field will need to determine if different menin inhibitors carry different toxicity risks in these triplet induction regimens for AML.

SENTRY: Frontline Selinexor Plus Ruxolitinib in Newly Diagnosed Myelofibrosis

The phase 3 SENTRY study investigated the addition of selinexor to standard frontline ruxolitinib therapy in patients with Janus kinase inhibitor–naïve myelofibrosis. The primary end points were spleen volume reduction of 35% or greater (SVR35) and absolute mean change in total symptom score (TSS; excluding fatigue) at week 24. 

The SENTRY trial randomized 235 patients to selinexor plus ruxolitinib and 118 patients to placebo plus ruxolitinib. Overall, 49.8% of patients in the selinexor arm versus 28% in the placebo arm achieved SVR35 by week 24 (OR, 2.58; 95% CI, 1.16-4.17; P < .0001). The 12-week, 36-week, and any-time SVR rates for selinexor versus placebo were 49.4% versus 20.3%, 46.9% versus 23%, and 67.7% versus 44.9%, respectively. Median change in spleen volume at week 24 was -40% with selinexor versus -26.7% with placebo. The mean absolute change in TSS at week 24 was -9.9 (95% CI, -11.2 to -8.6) with selinexor and -10.9 (95% CI, -12.6 to -9.1) with placebo (adjusted mean difference, 0.97; 95% CI, -1.07 to 3.02; P = .825).

After median follow-ups of 11.6 months in the selinexor arm and 12.6 months in the placebo arm, 95.3% and 89.8% of patients were alive, respectively. OS outcomes favored selinexor plus ruxolitinib (HR, 0.43; 95% CI, 0.19-1; nominal P = .022). Achievement of SVR35 predicted improved OS in a 24-week landmark analysis, mirroring data from the previous phase 1 study. 

While the addition of selinexor significantly improved SVR35 rate, it did not provide a commensurate benefit for TSS reduction compared with ruxolitinib alone. As such, whether this doublet will become the new standard of care for all newly diagnosed patients with myelofibrosis is unclear at this time, said Dr. Wang.