In a UK phase III trial (UKALL 2011) reported in the Journal of Clinical Oncology, Kirkwood et al found that a shorter duration of induction dexamethasone did not reduce steroid-related toxicity and that high-dose methotrexate (HDM) did not reduce central nervous system (CNS) relapse among patients younger than age 25 with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma.
Study Details
This multicenter dual randomization scheme trial enrolled a total of 2,750 eligible patients between April 2012 and December 2018; 1,902 were randomly assigned to Randomization 1 and 1,570 to Randomization 2. Randomization 1 compared induction dexamethasone for 28 days (6 mg/m2; standard) vs 14 days (10 mg/m2; short). Randomization 2 was a factorial randomization resulting in four arms: high-dose methotrexate (HDM) with vincristine pulses, HDM without pulses, standard interim maintenance (SIM) with vincristine pulses (standard of care), and SIM without vincristine pulses.
Key Findings
No differences in steroid-related toxicity were observed between the short vs standard dexamethasone groups (23.8% vs 25.5%, P = .41). No difference in CNS relapse was observed between SIM and HDM (hazard ratio [HR] = 0.98, 95% confidence interval [CI] = 0.65–1.49, P = .94), with 5-year rates of 5.3% vs 5.5%, respectively.
Bone marrow relapse in the no pulses group was noninferior to that in the pulses group (HR = 1.19, 95% CI = 0.87–1.62, P =.27). Event-free survival in the no pulses group was inferior to that in the pulses group (HR = 1.34, 95% CI = 1.05–1.73, P = .021), with no significant difference in relapse risk observed (HR = 1.24, 95% CI = 0.96–1.62, P = .10).
The investigators concluded: “Shorter duration of induction dexamethasone does not reduce steroid-related toxicity, and HDM does not improve CNS relapse within a UKALL treatment backbone. Omission of pulses is noninferior for bone marrow relapse.”
Ajay Vora, MBBS, FRCPath, of Great Ormond Street Hospital, London, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by a grant from Blood Cancer UK. For full disclosures of the study authors, visit ascopubs.org.
