AUDIO JOURNAL OF ONCOLOGY—Options Identified for Chemotherapy Intensity Reduction in Acute Lymphoblastic Leukemia Audio Journal of Oncology Podcast

Audio Journal of Oncology, February 14 2023, Reporting from the American Society of Hematology Annual Meeting (ASH), December 2022
An interview with Amy A. Kirkwood MSc, Senior Statistician at the Cancer Research UK & UCL Cancer Trials Centre, University College, London, UK
Interviewer: Peter M Goodwin
TITLE: Options Identified for in Acute Lymphoblastic Leukemia
NEW ORLEANS, USA—A big study conducted over an extended period of time has shown that there is scope for reducing the intensity of chemotherapy for patients with acute lymphoblastic leukema (ALL) and (the rarer) lymphoblastic lymphoma (LBL). Modifications to standard protocols offer scope for sparing many children the potential toxicity of full-does standard regimens without compromising cure rates.
Amy Kirkwood, Chief Statistician from University College, London tells the Audio Journal of Oncology (AJO) about her group’s findings from the randomized phase three UKALL 2011 study, reported (at the American Society of Hematology (ASH) 2022 Annual Meeting), showing that adjustments to current multi-agent chemotherapy regimens brought changes in outcome. She concludes that more gentle treatments may be possible for many patients while maintaining or improving efficacy for those at high risk.
https://ashpublications.org/blood/article/140/Supplement%201/516/488151/High-Dose-Methotrexate-Does-Not-Reduce-the-Risk-of
The treatment of ALL had improved hugely in the last 50 years, first author Amy A. Kirkwood MSc, Senior Statistician at the Cancer Research UK & UCL Cancer Trials Centre, University College, London, UK, told the AJO after giving her report at ASH. “We now have about 95 percent survival. About 15 percent of children will relapse. But we know that 50 years ago we were curing about 50 per cent of people with half the treatment. So, we know that we are overtreating large numbers of children,” she said.
So, trials were now looking at treatment reductions, and at trying to identify high-risk patients to design new ways of improving efficacy for that group only, she said. “We want to try and decrease treatment for the majority who will do well,” Kirkwood noted.
Specifically, the trial found that using high-dose methotrexate (HDM) did not improve central nervous system (CNS) relapse—contrary to some expectations. According to the UKALL 2011 study findings, it may have improved bone marrow relapse for some sub-groups of patients with B-lineage disease, however.
The trial also found that with some chemotherapy regimens the addition of monthly “pulses” of vincristine and dexamethasone (in the maintenance phase of treatment) had been un-necessary. They proved to be “non-inferior” for bone marrow relapse—compared with the standard practice of including such pulses. This suggested that pulse-free treatment could potentially be an option for some patients.
Study details
The UKALL 2011 study allocated patients to study arms in accordance with their risks, as stratified by National Cancer Institute (NCI) risk, cytogenetics and “end of induction minimum residual disease” (MRD). The aim was to assess whether elements of treatment could potentially be de-escalated without loss of efficacy. Randomizations were allocated within the several different standard “blocks” of chemotherapy.
Firstly, in the “induction” block of chemotherapy (aiming to get rid of most of the disease) there was a randomization between two different dose schedules of dexamethasone. A short (higher) dose schedule was compared with standard dexamethasone dosing. The aim had been to look at whether steroid dose could influence the incidence of side effects. This was followed by the “consolidation” block all in which all patients were treated the same.
Kirkwood said they saw no difference from steroid dosing schedule changes. “We were hoping to see a difference in steroid-related mo