Abstract
Background - Increased patient obesity rates have brought into question the need for dose adjustments in chemotherapy. Strategies for dose adjustments include using adjusted body weight (adjBW) versus total body weight (TBW) (Fair, 2017). Incorrect dosing of chemotherapy can result in significant complications. Underdosing has the potential to lead to treatment failure, whereas overdosing can result in increased toxicity. Currently, there is a lack of data regarding appropriate dose adjustments for conditioning chemotherapy regimens in patients with lymphoma who undergo autologous hematopoietic stem cell transplantation (AHCT) (Fair, 2017; Bubalo, 2014).
Objective - The primary objective of this study is to evaluate the effect of obesity on overall survival (OS) in lymphoma patients who have undergone AHCT. The secondary objectives are to evaluate progression-free survival (PFS), as well as safety and toxicity (particularly gastrointestinal, renal and liver toxicities, and infections).
Methods - Patients with lymphoma who received an AHCT were identified from our institutional database. Baseline patient characteristics and dose adjustments to conditioning chemotherapy regimens made in the setting of obesity were collected. Obesity was defined as actual body weight that is ≥ 125% Ideal Body Weight (IBW) as per Memorial Sloan Kettering Cancer Center allogeneic/autologous hematopoietic cell transplantation chemotherapy guidelines. Transplant outcomes (OS and PFS) and toxicities were compared between non-obese and obese patients. Sub-group analysis of the obese patient population compared those who received conditioning regimens based on adjBW versus TBW. Survival outcomes were estimated using the Kaplan-Meier method with differences assessed using a log-rank test. Differences in toxicity rates were assessed using a chi-square or fisher's exact test as appropriate.
Results - The 239 patients transplanted between January 2014 and August 2016 had a median age of 55.3 (range 19.1 - 77.1) and 44.8% were female. Their median Body Mass Index was 27.3 kg/m2 (range 16.8 - 53.2). Baseline characteristics of patients are summarized in Table 1, and the subset of obese patient characteristics are summarized in Table 2. Of the obese patients (N=110, 46.0%), 29.1% received chemotherapy based on adjBW. PFS and OS did not differ significantly between the non-obese group and the obese group (3-year PFS - 69.8% vs. 74.3%, P=0.25; 3-year OS - 85.7% vs. 89.7%, P=0.42). The median follow-up of surviving patients was 36.1 months. Within the obese group, PFS and OS were significantly longer in the group that received conditioning chemotherapy dosed on TBW than adjBW (3-year PFS - 84.3% vs. 49.9%, P<0.001; 3-year OS - 97.0% vs. 71.9%, P<0.001). Toxicities were graded according to the NCI Common Technology Criteria for Adverse Effects v4.0 (CTCAE). Most toxicity outcomes were similar between the non-obese and obese groups. The rate of grade 3 or 4 liver toxicity was significantly higher in the non-obese group than the obese group (5.4% vs. 0%, P=0.02). In the obese group, there were no reported grade 3 or 4 renal toxicities. No significant differences were observed between the TBW and adjBW groups for grade 3 or 4 infections (89.7% vs. 78.1%, P=0.13) or gastrointestinal toxicities (56.4% vs. 34.4%, P=0.06), potentially related to sample size. Multivariate analyses controlling for significant between-group differences in baseline characteristics are pending.
Conclusion - Among obese adults with lymphoma undergoing an AHCT, conditioning chemotherapy dosed on TBW was associated with longer overall survival and progression-free survival than chemotherapy dosed on adjBW, without increased rates of toxicities.
No relevant conflicts of interest to declare.
