The addition of tafasitamab-cxix (Monjuvi) to dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) with or without rituximab (Rituxan) led to measurable residual disease (MRD) negativity following cycle 1 in nearly half of evaluable patients with newly diagnosed Philadelphia chromosome (Ph)–negative B-cell acute lymphoblastic leukemia (B-ALL), meeting the primary end point of an investigator-initiated phase 2 study (NCT05453500).1
Data presented at the
At a median follow-up of 10.8 months (range, 0.7–36.9), the 1-year event-free survival (EFS) rate was 72.8% (95% CI, 50.4%–86.4%), the 1-year relapse-free survival (RFS) rate was 71.0% (95% CI, 47.6%–85.5%), and 1-year overall survival (OS) rate was 80.2% (95% CI, 54.6%–92.3%).
Four relapses occurred, including 2 patients who were post–hematopoietic stem cell transplant (HSCT). All 4 patients were CD19-positive, and none involved the central nervous system (CNS). Six patients died, including 4 from non-relapse causes (3 post-HSCT) and 2 from refractory B-ALL; no deaths were attributed to study treatment.
“DA-EPOCH with or without rituximab plus tafasitamab yields higher rates of MRD negativity than historical controls,” lead study author Ryan D. Cassaday, MD, of Fred Hutch Cancer Center and University of Washington Medicine in Seattle, and colleagues wrote in a poster presentation of the data.
Investigators enrolled patients 18 years of age or older with CD19-positive, Ph-negative B-cell ALL.1,2 Patients with Burkitt lymphoma/leukemia were excluded.2 No prior systemic therapy for ALL was permitted, except to control acute symptoms and/or hyperleukocytosis. Patients were not allowed to have isolated extramedullary or known parenchymal central nervous system (CNS) disease.
Enrolled patients received DA-EPOCH with or without rituximab, plus tafasitamab at 12 mg/kg intravenously, on days 1, 8, and 15 of each 21-day cycle for up to 8 cycles.
The primary end point was MRD negativity after cycle 1 by MFC at a 10⁻⁴ sensitivity. The study required at least 13 of 30 evaluable patients (43%) to be MRD-negative after cycle 1, compared with a historical rate of 28% with DA-EPOCH with or without rituximab alone, with 80% power and a one-sided alpha of 0.05.
Patient demographics among 30 evaluable participants included a median age of 67 years (range, 44–84), with 50% of patients 70 years of age or older. Poor-risk cytogenetics per National Comprehensive Cancer Network criteria were present in 57% of patients, and 43% had received prior chemotherapy or radiation. Eleven patients (37%) received rituximab as part of the DA-EPOCH backbone.
Infusion reactions were the most notable toxicity, occurring in 73% of evaluable patients. Of 28 total infusion reactions, 89% occurred during cycle 1, and 96% occurred on day 1 of the infusion. Most reactions required a temporary interruption (79%) or no action (21%). Clinical manifestations were reversible and included vital sign changes, flushing, chills, rash, and nausea.
Grade 3 or higher non-hematologic adverse effects (AEs) observed in more than 2 evaluable patients included febrile neutropenia (n = 12), infections (n = 9), hypotension (n = 9), low fibrinogen (n = 6), hypoxia (n = 4), syncope (n = 4), and atrial fibrillation (n = 3). Infections included bacterial pneumonia, skin and soft tissue infections, and infectious enterocolitis (each in multiple patients), as well as a brain abscess in 1 patient.
CNS disease was detected in 7 patients overall. Initial CSF assessment by MFC identified 3 patients with CNS involvement, while HTS of CSF identified 4 additional patients not detected by conventional MFC. All 7 cases resolved with intrathecal therapy.
