Feasibility and preliminary efficacy of a Mediterranean diet and home-based exercise intervention during chemotherapy for lymphoma survivors: The life-l study

Abstract Introduction: Lymphoma patients undergoing chemotherapy often face toxicities that affect treatment completion and quality of life. While evidence from solid tumors suggests diet and exercise may ease chemotherapy-related symptoms and improve tolerance, these effects remain understudied in hematologic malignancies such as Hodgkin and non-Hodgkin lymphomas. Here, we report interim results from the Lifestyle Intervention of Food and Exercise for Lymphoma Survivors (LIFE-L) randomized clinical trial, focusing on patient-reported outcomes (PROs) and physical function measures during chemotherapy. Methods: The LIFE-L is an ongoing two-arm randomized waitlist-controlled trial (NCT05839210) evaluating the effects of a Mediterranean diet and a home-based strength and aerobic exercise intervention on chemotherapy relative dose intensity (RDI) in adults undergoing standard 6-cycle combination chemotherapy regimens for newly diagnosed Hodgkin or non-Hodgkin lymphomas. Participants are randomized 2:1 to the intervention or waitlist control group prior to treatment initiation. The intervention consists of individualized weekly remote coaching sessions with a dietitian and exercise physiologist throughout chemotherapy. Feasibility of the study was defined as at least 50% of eligible survivors agreeing to participate, retention as completion of at least 80% of intervention sessions, and satisfaction as 80% or more of participants reporting satisfaction during structured exit interviews. PROs were assessed using the PRO-CTCAE and PROMIS Global Health questionnaires and included fatigue, pain, shortness of breath, anxiety, depression, and constipation. Physical functioning was measured using handgrip strength and the Short Physical Performance Battery (SPPB). Study assessments were conducted during routine clinic visits at baseline, prior to chemotherapy cycles 3 and 6-, and four-weeks post-treatment. Descriptive statistics were used to summarize demographic characteristics and interim results for these outcomes. Results: In the current analytic sample of 72, 44 (61%) patients were in the intervention arm and 28 (39%) in the control. The median age was 54 years (range: 18–82), with 40% identifying as female and 75% as Hispanic White. The sample included 69% with non-Hodgkin lymphoma and 31% with Hodgkin lymphoma. Feasibility was demonstrated by a high enrollment rate of 81% of eligible patients enrolling in the study and intervention adherence, with attendance rates of 86% for diet sessions and 81% for exercise sessions. At the post intervention timepoint, participants in the intervention group reported lower rates of moderate to very severe symptoms compared to the control group, including anxiety (17% vs. 34%, p-value = 0.09), depression (46% vs. 67%, p-value = 0.08), pain (22% vs. 39%, p-value = 0.10), fatigue (46% vs. 67%, p-value = 0.08), and constipation (17% vs. 25%, p-value = 0.42). The proportion of participants reporting moderate to severe shortness of breath was similar between groups (14%, p-value = 0.96). Measures of physical function indicated that the intervention group had higher handgrip strength (30.2 kg vs. 23.2 kg, p-value = 0.02), higher SPPB scores (9.5 vs. 8.8, p-value = 0.23), with higher SPPB gait scores (3.5 vs 3.0, p-value = 0.04) compared to the control group, indicating overall better physical function. Results will be re-evaluated upon completion of the trial and final analyses will include primary outcomes of chemotherapy RDI and survival. Conclusion: Preliminary feasibility of the trial is supported by high enrollment and adherence rates among lymphoma survivors. Interim analyses indicate that participants receiving the intervention reported lower rates of moderate to severe symptoms and exhibited improved physical function compared to controls. These early findings underscore the potential of lifestyle interventions to mitigate symptom burden and enhance physical function outcomes during lymphoma treatment. Given the trial remains ongoing, additional data are needed to fully determine the intervention's efficacy.