Tafasitamab plus DA-EPOCH ± R in newly diagnosed Ph− B-ALL

A phase II trial (NCT05453500) is evaluating the addition of tafasitamab to dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) ± rituximab (R) in adults with newly diagnosed (ND) Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph− B-ALL) not eligible for pediatric-inspired regimens.¹ In the trial, patients with ND Ph− B-ALL receive DA-EPOCH (+ R if CD20+), with intrathecal chemotherapy given on Day 1–5 every 21 days for up to Cycle 8. Tafasitamab is given at 12 mg/kg IV on Days 1, 8, and 15 in each cycle. Initial results for 17 evaluable patients from this trial were presented by Noam Kopmar at the 2025 ASCO Annual Meeting. The primary endpoint was MRD-negativity (<0.01%) by multiparameter flow cytometry after Cycle 1; secondary endpoints included overall survival, event-free survival, and safety.¹

Key learnings 

MRD-negativity (≤0.01%) was achieved in 41% and 71% of patients at C1 and C4, respectively. The morphologic CR rate was 76%.

With a median follow-up of 9.2 months, the median OS was not reached, and the median EFS was 20.7 months.

The most common Grade ≥3 non-hematologic TRAEs were fibrinogen decrease (n = 5), infections (n = 5), febrile neutropenia (n = 4), hypotension (n = 3), and syncope (n = 2); Grade 4 AEs were sepsis and intracranial hemorrhage (n = 1 each).

The addition of tafasitamab improved early MRD response compared with historical data and met the C1 MRD-negativity target, supporting the continuation of this phase II trial.