Weight Change Trends and Impact of Body Mass Index (BMI) on Outcomes in Patients with Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma, a Retrospective Analysis from the Lymphoma Innovations Orien Network (LION) Consortium

Introduction. Several studies have examined the impact of BMI on outcomes in B-cell non-Hodgkin lymphoma (B-NHL) but most focused on the impact of pretreatment BMI on outcomes in newly diagnosed patients. In addition, data on weight change patterns during treatment in B-NHL are limited. Herein, we report weight change patterns during sequential lines of treatment and the impact of BMI on outcomes in patients with r/r aggressive large B-cell lymphoma (LBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL).

Methods. Patients with r/r LBCL, FL or MCL were identified through LION, a consortium of 7 US academic institutions that prospectively collects molecular and clinical data on adult patients with r/r B-NHL. Patients with available weight data at time of initiation of the 2^nd (Wt-2) and/or 3^rd (Wt-3) line of treatment were included. Changes in weight were categorized into no change (-5% to 5%), decrease (≥-5%), or increase (≥5%) from prior line of therapy. Outcomes were evaluated for the 1^st three lines of treatment, with the corresponding event-free survival (EFS) for each line of treatment calculated from treatment initiation until progression, new treatment, or death due to any cause; lymphoma-specific survival (LSS) from treatment initiation until death due to lymphoma; and overall survival (OS) from treatment initiation until death from any cause.

Results. Of 614 patients, 413 (67.2%) had available Wt-2 (n=354) and/or Wt-3 (n=245) and were included. LBCL was the most common lymphoma subtype (n=193, 46.7%) followed by FL (n=146, 35.3%) and MCL (n=74, 17.9%) (Table). The baseline characteristics at diagnosis for the overall cohort were: median age 60 years (range 17-86), male 60%, White 89% (available n=400), Black 9%, stage III/IV 85% (available n=377), elevated LDH 48% (available n=179), B symptoms present 30% (available n=339), weight loss as a B symptom 11% (available n=413), and performance status ≥2 10% (available n=219). Most patients (n=327, 80%) received chemoimmunotherapy as their first-line treatment (available n=412) and 43% relapsed within 1 year of first treatment.

At time of initiation of 1^st, 2^nd and 3^rd lines of treatment, most patients were either overweight (BMI=25-29.9) (37%, 31%, and 36% respectively) or obese (BMI ≥30) (37%, 42%, and 37%, respectively). Weight changes between sequential lines of treatment were common: between 1^st and 2^nd line treatments (available n=214): 49 patients (23%) had weight decrease, 104 (49%) no change, and 61 (29%) increase; between 2^nd and 3^rd line treatments (available n=186): 43 patients (23%) had weight decrease, 113 (61%) no change, and 30 (16%) increase. Higher BMI prior to initiation of 3^rd line treatment was associated with LSS with overweight and obese patients having superior LSS compared with patients with normal BMI (hazard ratio (HR): 0.27 (95% confidence interval (CI), 0.08-0.89), p=.031 and HR=0.32 (95%CI 0.11-0.95), p=.04, respectively) (Figure). BMI prior to initiation of 1^st, 2^nd, or 3^rd lines of treatment was not significantly associated with outcomes otherwise. Weight changes between sequential lines of treatment were not significantly associated with EFS, LSS, or OS.

Conclusions. Obesity is common among patients with r/r B-NHL. Weight changes during sequential lines of treatment are also common in patients with r/r B-NHL with approximately 40-50% of patients losing or gaining ≥5% of their pretreatment body weight. However, these weight changes were not associated with outcomes in our study. Finally, patients with higher BMI (overweight or obese) prior to initiation of third-line treatment had a significantly lower risk of death from lymphoma compared with patients with normal BMI.

Sawalha:Celgene/BMS: Research Funding; BeiGene: Research Funding; Epizyme: Consultancy; TG Therapeutics: Research Funding. Churchman:M2Gen: Current Employment. Stephens:AbbVie: Consultancy; Newave: Research Funding; AstraZeneca: Consultancy; CSL Behring: Consultancy; Beigene: Consultancy; Epizyme: Consultancy; Celgene: Consultancy; Genentech: Consultancy; Lilly: Consultancy; TG Therapeutics: Consultancy; Novartis: Research Funding; Mingsight: Research Funding; Karyopharm: Research Funding; JUNO: Research Funding; Arqule: Research Funding; Acerta: Research Funding. Pinilla Ibarz:SecuraBio: Research Funding; AstraZeneca: Consultancy; AbbVie: Consultancy; Pharmacyclics: Consultancy; Janssen Pharmaceuticals: Consultancy. Maddocks:Acerta: Consultancy; Celgene: Consultancy; Lilly: Consultancy; Incyte: Consultancy; Morphosys: Consultancy; Genentech: Consultancy; ADC Therapeutics: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy; Janssen: Consultancy; Genmab: Consultancy; Beigene: Consultancy; Kite: Consultancy; Abbvie: Consultancy; BMS: Consultancy, Research Funding; Pfizer: Research Funding; Pharmacyclics: Consultancy, Research Funding. Link:Novartis: Research Funding; MEI: Consultancy; Jannsen: Research Funding; Bristol-Myers Squibb: Research Funding; Genentech / Roche: Consultancy, Research Funding. Cohen:Genentech: Research Funding; Astrazeneca: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Janssen: Consultancy; Novartis: Research Funding; Lilly Oncology/Eli Lilly: Consultancy, Research Funding; HutchMed: Consultancy, Research Funding; Takeda: Research Funding; Aptitude Health: Consultancy; BMS/Celgene: Research Funding; Kite Pharma/Gilead: Consultancy.