Phase II study of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) ± rituximab (R) + tafasitamab (tafa) in adults with newly diagnosed (ND) Philadelphia chromosome–negative (Ph-) B lymphoblastic leukemia (B-ALL).

Abstract

6535 Background: For adults with ND Ph- B-ALL, frontline regimens now often include the CD19/CD3 bispecific blinatumomab (blin). However, blin administration is challenging, particularly for less-experienced centers. DA-EPOCH ± R is safe and active in these patients (pts; Cassaday, et al, Leuk Lymphoma , 2023) and easier to deliver. Tafa is a CD19 monoclonal antibody active in B-cell lymphomas. We hypothesized that the addition of tafa to DA-EPOCH ± R will yield higher rates of measurable residual disease negativity (MRD-) without increasing toxicity or administration complexity. Methods: This is a phase II investigator-initiated study (NCT05453500) in adults (>18 years) with ND CD19+ Ph- B-ALL not eligible for a pediatric regimen. DA-EPOCH ± R was given as cited above; tafa 12 mg/kg was given IV on day (d) 1, 8, and 15 of each cycle (C). After blin consolidation was FDA approved, pts could receive this off-study. The primary endpoint was MRD- by multiparameter flow cytometry (MFC) per EuroFlow (~<10 -4 ) after C1 (~d 20); secondary endpoints included MRD- by MFC after C4 (~d 80); non-hematologic adverse events (AEs, CTCAE v5); and relapse-free (RFS) and overall survival (OS). Exploratory endpoints included high-throughput sequencing (HTS; <10 -6 ) by clonoSEQ in marrow and cerebrospinal fluid (CSF). If ³13 of 30 evaluable pts (³43%) are MRD- after C1, the primary endpoint is met (vs 28% with DA-EPOCH ± R alone; 80% power and one-sided α = 0.05). Results: From 3/2023 to 12/2025, 30 pts enrolled: 2 pts did not finish C1 due to grade (G) 4 AST elevation (related) and G5 C. perfringens sepsis (unrelated); 27 were evaluable for response and are the focus here. Median age was 67 (44-84), 70% male, 56% poor risk cytogenetics by NCCN, and 9 received R. Complete response (CR) rate was 85% (23/27); MRD- by MFC after C1 was 44% (12/27) and 80% (20/25) by C4 in pts with sufficient follow-up (f/u). In pts MRD- by MFC, 53% (8/15) were MRD- by HTS. Other G3+ AEs seen in >2 pts: infection (9); febrile neutropenia (8); low fibrinogen (6); hypotension (5); and syncope (4). Initial CSF MFC was positive in 3 pts; HTS was positive in these plus 4 more (7 total). With a median f/u among survivors of 10 mo (1-37), there were 3 relapses: 1 post-HCT and 1 after only 2 treatment cycles; all were CD19+, and 0 involved CNS. Only 2 pts got blin consolidation. 6 pts died: 4 non-relapse causes (3 post-HCT) and 2 from refractory ALL. No deaths were due to study treatment. 1-year RFS and OS were estimated to be 67% and 76%, respectively. Conclusions: DA-EPOCH ± R + tafa yields high rates of MRD-. Follow-up is immature, but early survival rates are comparable to more complex strategies. This study is on pace to reach its primary endpoint, with enrollment ending before the conference. HTS on CSF can identify CNS disease more frequently. Clinical trial information: NCT05453500 .