Beyond MRD: The importance of weight recovery in adults with ALL

Abstract Background: The treatment of acute lymphoblastic leukemia (ALL) in adults has improved with pediatric-inspired regimens such as mCALGB 10403. However, the use of high-dose steroids and L-asparaginase significantly affects patients' weight during therapy. In children, both obesity and significant weight loss have been associated with worse outcomes, but these effects are poorly characterized in adults. Methods: A retrospective, observational study was conducted on 123 adult patients (18–52 years) with ALL treated with mCALGB 10403 between February 2017 and June 2025. Only those with at least one post-induction weight measurement were included. Patients treated with different regimens were excluded. Results: Ninety-nine patients had adequate follow-up. Median age was 27.5 years (IQR 21–36); 59% were males. At diagnosis, 58.2% had overweight/obesity and 9.4% had diabetes. Median weight before beginning chemotherapy was 70 kg (IQR 60–79.75). During induction, patients experienced significant weight loss (median 6 kg, equivalent to 9.9% of baseline weight). Weight loss >8% was associated with increased risk of grade 3–4 hepatotoxicity (64.2% vs. 37.8%; OR 2.94, 95% CI: 1.23–7.02; p = 0.018). At the start of maintenance (POMP6), 75% of patients regained weight (median +8 kg; +14%). Regaining >5% of baseline weight was associated with a lower relapse rate (19% vs. 50%, p = 0.027). Two-year overall survival (OS) was significantly higher in those who regained ≥5% at POMP6 (85% vs 35.8%, p=0.001), which is independent of post-induction measurable residual disease (MRD): Weight gain ≥5%: HR 0.195 (95% CI: 0.063–0.605; p=0.005) MRD >0.1%: HR 3.697 (95% CI: 1.210–11.86; p=0.022). Patients that developed diabetes after consolidation were older (35 vs 26 years, p=0.044) and more likely to be overweight at diagnosis (90% vs 42.6%, p<0.001). Conclusion: Significant weight loss during treatment is associated with increased toxicity and worse survival outcomes. On the other hand, increasing ≥5% of weight by maintenance correlates with better prognosis, regardless of MRD. Failure to regain weight may reflect aggressive disease or prolonged toxicity, possibly linked to sarcopenia rather than appropriate metabolic state. Weight may be useful as a simple and meaningful marker of recovery and prognosis in adult ALL.