Four Doses of Rituximab Plus Induction Therapy Does Not Improve EFS in Patients With ALL

Four doses of rituximab plus standard induction therapy did not significantly improve event-free survival (EFS) over standard of care induction alone for patients with de-novo acute lymphoblastic leukemia (ALL), according to UKALL14, a UK National Cancer Research Institute group study.

“Rituximab is beneficial in ALL but 4 doses during induction is likely to be insufficient. However, we found a possibly clinically beneficial 8% improvement in EFS at 3 years and a 15 month longer median EFS in the investigational group. The benefit we observed appears to result from a reduction in relapse rate, as opposed to a better early response,” wrote David Marks, PhD, United Bristol Healthcare Trust, UK, and co-investigators.

In UKALL14, 586 de novo B-precursor cell ALL patients from 65 UK National Health Service Centers were randomly assigned to standard of care or standard of care plus rituximab between April 19, 2012, and July 10, 2017. Patients with both BCR-ABL1-negative and -positive status could be included, depending on age. Almost two-thirds of both cohorts (60%, 59%) had high-risk cytogenetics.

Patients received standard-of-care induction therapy or standard-of-care induction therapy plus 4 doses of intravenous rituximab (375 mg/m² on days 3, 10, 17, and 24). The median follow-up was 53.7 months (IQR 40.3 – 70.4).

The 3-year EFS was 51.4% (45.4 – 57.1) in the treatment arm compared with 43.7% (95% CI, 37.8 – 49.5) for the standard of care group (HR 0.85; 95% CI, 0.69 – 1.06; P = .14).

In the treatment arm, the 3-year non-relapse mortality was 20.6% (16.2–25.9), but higher at 23.7% (95% CI 19–29.4) for those in the standard-of-care group (HR 0.88; 95% CI, 0.62 – 1.26; P = .49).

The frequency of fatal adverse events in the induction phases was about the same in both groups (5%, 4%).

Source:

Marks D, Kirkwood A, Rowntree C, et al. Addition of four doses of rituximab to standard induction chemotherapy in adult patients with precursor B-cell acute lymphoblastic leukaemia (UKALL14): a phase 3, multicentre, randomised controlled trial. Lancet Haematol. 2022 Apr;9(4):e262-e275.