An intervention involving caloric and nutrient restriction was able to reduce fat gain in overweight and obese young patients with B-cell acute lymphoblastic leukaemia (B-ALL) undergoing induction chemotherapy, and reduced minimal residual disease (MRD) after induction therapy, according to a new study.
The negative impact of obesity on outcomes in B-ALL is now well described. “Prolonged glucocorticoid chemotherapy and sedentary behaviour during the first month of therapy (induction) further compound this problem by causing rapid gains in fat,” wrote study authors led by Dr Etan Orgel, of the Cancer and Blood Disease Institute at the Children’s Hospital Los Angeles, in Blood Advances.
Other research has also shown that being obese during therapy for B-ALL can increase the risk for relapse by 50%, decreasing survival in both children and adults. However, observations made previously in mice have suggested that an intervention targeting obesity may reverse some of its negative effects.
The new IDEAL trial tested an intervention designed to induce a caloric deficit of at least 20%, using both reduced caloric intake and increased exercise. It included a total of 40 patients aged 10 to 21 years old undergoing induction therapy for B-ALL; they compared these to a recent historical control group of 80 patients.
Overall, the intervention did not significantly reduce the median change in fat mass from baseline, at +5.1% compared with +10.7% in the control group (p = .13). However, the intervention did provide benefit in patients who were overweight or obese, with a fat mass change of +1.5% compared with +9.7% (p = .02).
The intervention was feasible, with better than 75% adherence to the overall diet with more than 80% of patients completing all trial visits.
The intervention also increased circulating adiponectin, and reduced insulin resistance in patients. And importantly, it significantly reduced the risk of MRD after induction therapy, with an odds ratio of 0.30 (95% CI, 0.09-0.92; p = .02).
This was the first prospective trial to test a caloric restriction and exercise intervention as a way to improve chemotherapy efficacy in a haematologic malignancy. Though the trial was not designed to test the intervention’s effect on long-term outcome, the reduction in MRD risk is clearly important, the authors wrote, as it remains the strongest patient-level predictor of poor outcome.
“The IDEAL trial provides proof of principle for the feasibility and biologic plausibility of breaking the link between overweight physiology and tumor biology to improve chemotherapy efficacy, disease response, and survival in ALL: all without added morbidity or mortality,” the authors concluded.