High proportions of long-term survivors of non-Hodgkin lymphoma (NHL) experience severe fatigue, though this fatigue did not appear to correlate with initial treatment or receipt of rituximab, according to results from the Lymphoma Study Association’s SIMONAL cross-sectional study (ClinicalTrials.gov Identifier: NCT02849912) published in Cancer. Severe fatigue was, however, correlated with age, obesity, and the presence of other comorbidities.

Long-term survivors of NHL deal with treatment toxicity and complications in addition to late toxicities. These late toxicities should be considered when assessing the risk-to-benefit ratio of rituximab.

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In this study, 1671 patients (906 men and 765 women) with a median age of 64 years (range: 24-95) completed 2 self-administered questionnaires, the 20-item Multidimensional Fatigue Inventory (MFI-20) and a Life Situation Questionnaire.

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Participants were identified from 12 consecutive clinical trials conducted by the Lymphoma Study Association between 1993 and 2010. MFI-20 scores of at least 60 on dimension scales that were scored from 0 to 100 defined severe fatigue.

Over one-third of patients (37%; 95% CI, 35%-40%) experienced severe fatigue. Higher levels of fatigue were correlated with obesity, increased age, and the presence of comorbidities (P <.001 for each). Female patients more frequently reported severe fatigue compared with male patients, including reduced motivation (14% vs 8%; P <.001), physical fatigue (26% vs 18%; P =.001), and general fatigue (32% vs 23%; P <.001).

Severe fatigue was not correlated with initial treatment, rituximab exposure, histologic type, relapse, or receipt of autologous stem cell transplant (ASCT). Initial therapy included upfront ASCT (342 patients); cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)-like chemotherapy (811 patients); and high-dose CHOP (518 patients). A total of 829 patients also received rituximab.

Survivors of NHL were more likely to experience higher levels of fatigue compared with the general population across all dimensions except reduced activity (P <.001). Approximately two-thirds (66%) of patients reported 1 or more late health disorders.

“In conclusion, the current study can be considered as a real-life picture of the health status of NHL survivors that can be used in decision making. The findings confirm that fatigue represents a major concern in long-term survivors of NHL,” wrote the authors. However, they cautioned, “Before various tertiary prevention interventions to manage or prevent the development of long-term fatigue are undertaken, the biologic origin of persistent fatigue should be questioned.”


1. Mounier N, Anthony S, Busson R, et al. Long-term fatigue in survivors of non-Hodgkin lymphoma: the Lymphoma Study Association SIMONAL cross-sectional study [published online March 22, 2019]. Cancer. doi:10.1002/cncr.32040