The addition of 4 doses of rituximab to standard induction chemotherapy did not show significant improvement in the event-free survival (EFS) compared with standard of care (SOC) in adult patients with precursor B-cell acute lymphoblastic leukemia (ALL), results of phase 3 UKALL14 study showed.
“Rituximab is beneficial in [ALL] but four doses during induction is likely to be insufficient,” the researchers wrote in their report, published in The Lancet Haematology.
Despite the lack of improvement in EFS, rituximab was found to be safe for all ages of patients without additional toxicity, even among those in whom allogeneic hematopoietic stem-cell transplantation was a subsequent therapy.
UKALL14 was an investigator-initiated, phase 3 trial (ClinicalTrials.gov Identifier: NCT01085617) that was conducted at 65 National Health Service Centers in the UK to investigate whether adding rituximab to SOC would be beneficial for treating patients with de novo B-precursor ALL.
Between April 19, 2012, and July 10, 2017, the study enrolled 586 patients who were randomly assigned 1:1 to receive SOC induction therapy (n=292) or SOC induction therapy plus 4 doses of intravenous rituximab (375 mg/m² on days 3, 10, 17, and 24) (n=294). In the final analysis, 4 patients in the SOC arm and 5 patients in the SOC plus rituximab arm were excluded due to misdiagnosis.
In the SOC arm, the median age of the patients was 45 years (interquartile range [IQR], 22-65); 55% were men, and 59% had high-risk cytogenetics. In the SOC plus rituximab arm, the median age was 46 years (IQR, 23-65); 55% were men, and 60% had high-risk cytogenetics.
After a median follow-up of 53.7 months (IQR, 40.3-70.4), the median EFS was 23.2 months in the SOC arm and 38.8 months in the SOC plus rituximab arm.
Researchers reported larger treatment effects on EFS for patients with BCR-ABL-positive than BCR-ABL-negative disease, with a significant difference for bone marrow relapses.
The team did not observe a statistically significant difference in the 3-year EFS between the SOC arm (43.7%) and the SOC plus rituximab arm (51·4%) (hazard ratio [HR], 0.85; 95% CI, 0.69-1.06; P =.14).
Likewise, there was no significant difference in the overall survival rate between the 2 treatment arms (HR, 0.88; 95% CI, 0.70-1.11; P =.29).
Adding rituximab to SOC also did not seem to affect non-relapse mortality. The 3-year non-relapse mortality rate was similar between the SOC arm (23.7%) and the SOC plus rituximab arm (20.6%), with no statistically significant difference (HR, 0.88; 95% CI, 0.62-1.26; P =.49).
At the end of both phases of induction, no significant difference was observed between the 2 treatment arms in the proportion of patients who achieved complete remission or those in molecular remission.
Regarding safety, the most common adverse events (AEs) included infections and cytopenias, with no difference in the rates of AEs between the 2 study arms. Grade 5 AEs occurred in 4% of the patients in induction phases 1 and 2 in the SOC arm and 5% of the patients in the SOC plus rituximab arm.
In conclusion, the researchers stated, “The full benefit of rituximab in patients with [ALL] is likely to require more prolonged administration of rituximab, as demonstrated by the GRAALL [randomized] controlled trial.”
Disclosure: This research was supported by Cancer Research UK and Blood Cancer UK.
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. Published online April 1, 2022. doi: 10.1016/S2352-3026(22)00038-2