Tafasitamab (MONJUVI/MINJUVI) is an Fc-enhanced anti-CD19 monoclonal antibody developed by MorphoSys and Incyte and approved in combination with lenalidomide for certain patients with diffuse large B-cell lymphoma. Given the broad expression of CD19 across B-cell malignancies, investigators have explored its potential role in acute lymphoblastic leukemia, particularly as a more accessible immunotherapy option compared with continuous-infusion bispecific antibodies.

This Phase II investigator-initiated trial evaluated the addition of tafasitamab to DA-EPOCH ± rituximab in adults with newly diagnosed CD19-positive Ph-negative B-ALL who were not candidates for pediatric-inspired treatment regimens. The study was designed to determine whether the incorporation of tafasitamab could improve early MRD clearance without compromising feasibility or safety. Between March 2023 and January 2026, 31 patients were enrolled, with 29 evaluable for efficacy.

CNS Disease Assessment:

• Initial CSF flow cytometry positivity was observed in 3 patients.

• High-throughput sequencing (HTS) identified these 3 patients plus an additional 4 patients with detectable disease in CSF.

• A total of 7 patients had CSF disease detected by HTS.

Safety Outcomes-

• Other Grade 3+ AEs seen in >2 patients included febrile neutropenia (10); infection (9); hypotension (8); low fibrinogen (6); hypoxia (4); atrial fibrillation (3); and syncope (3). 

• 6 patients died: 4 non-relapse causes (3 post-HCT), 2 refractory ALL, and 0 from study treatment.

KOL Insights-

“The incorporation of CD19-directed monoclonal antibody therapy into DA-EPOCH appears feasible and resulted in encouraging MRD-negativity rates in a population not eligible for pediatric-inspired regimens.”– Expert Opinion

“The observation that HTS detected additional CSF disease beyond standard flow cytometry warrants further investigation into its role in CNS disease assessment.”– Expert Opinion

Conclusion-

Philadelphia chromosome-negative B-cell ALL represents the majority of adult ALL cases. While treatment outcomes have improved substantially through the incorporation of immunotherapies and MRD-guided treatment strategies, many patients remain ineligible for intensive pediatric-inspired regimens, creating a need for effective and practical frontline alternatives.

This Phase II study demonstrated that adding tafasitamab to DA-EPOCH ± rituximab achieved high rates of MRD negativity and met its predefined primary endpoint in newly diagnosed adults with Ph-negative B-ALL. Early survival outcomes were encouraging, and no new safety concerns emerged. Although follow-up remains immature, these findings support continued evaluation of CD19-directed antibody-based approaches as potentially accessible frontline immunotherapy strategies in adult ALL.