Lymphoma Treatment Alterations in the Context of Autoimmune Disease
Authors: McGue Shannon , Sitlinger Andrea , Chang Sophia , Wang Annie , Thomas Samantha , Wang Jie 
Published: December 2023

Background: Autoimmune disease (AD) confers an increased risk for lymphoma. Several studies have shown that pre-existing AD portends a worse prognosis for lymphoma patients, but the reasons for this are unknown. 1,2,3 We hypothesize that one reason may be poor treatment tolerance in AD patients due to concurrent risk for cytopenias, infections, and immune-related adverse events.

Methods: We conducted a retrospective cohort study to understand whether AD is associated with higher risk for treatment alterations, hospitalizations, and transfusions among lymphoma patients. The study population consisted of adult patients (aged 18-74 at lymphoma diagnosis) who underwent lymphoma treatment at one tertiary care center from 2017-2022. Patients who developed AD after or within the 12 months before lymphoma diagnosis were excluded to avoid including patients whose AD was paraneoplastic or a treatment side effect. Subjects were found by using cohort builder in electronic medical record then reviewing records for eligibility. The primary exposure of interest was pre-existing diagnosis of AD and the primary outcome was treatment alteration, such as dose reduction, delay, or discontinuation. The secondary outcomes were hospitalization, and transfusion. Outcomes were compared between groups with non-parametric tests. Logistic regression was used to estimate the association of AD with any treatment alteration.

Results: We reviewed 357 records, with 30 eligible for inclusion in AD cohort and 65 eligible for non-AD cohort. There were 17 different lymphoma types with diffuse large B cell lymphoma as the most common (10 in AD cohort, 20 in non-AD). In the AD cohort, there were 12 distinct autoimmune diagnoses and rheumatoid arthritis was the most common (n=11). Baseline patient characteristics did not differ between the AD and non-AD cohorts in age, sex, diagnosis, stage, renal function, hemoglobin or type of treatment received. However, patients in the AD cohort were more likely to be Black or Asian compared to the non-AD cohort (Table 1). There were no differences in frequency of treatment alterations, unplanned hospitalizations, or incidence of transfusion between the AD and non-AD groups. Logistic regression showed no association of study group with incidence of any treatment alteration, even after controlling for baseline characteristics.

Discussion: This study examines whether autoimmune disease impacts treatment tolerance among lymphoma patients. In a Swedish retrospective study of lymphoma, worse outcomes were seen among patients with AD due to increased non-lymphoma risk of death, suggesting that AD patients may have more frequent serious and life-threatening complications from lymphoma therapy. 1 In our study, there were no differences in treatment tolerance between the AD and non-AD groups. However, sample size is a limitation, and chart review is ongoing. Notably, treatment alterations were common in both groups, and no increase in unplanned hospitalizations was seen in the AD group. Clinical decisions to dose reduce, delay or discontinue therapy may mitigate against hospitalization from serious treatment related complications even in lymphoma patients with concurrent AD. Future directions include examining interactions between treatment alterations, autoimmune disease, and prognosis in specific lymphoma subtypes.

1. Simard JF, Baecklund F, Chang ET, Baecklund E, Hjalgrim H, et al. Lifestyle factors, autoimmune disease and family history in prognosis of non-hodgkin lymphoma overall and subtypes. Int J Cancer. 2013 Jun 1;132(11):2659-66. doi: 10.1002/ijc.27944. Epub 2012 Dec 3. PMID: 23160780.

2. Jachiet V, Mekinian A, Carrat F, Grignano E, Retbi A, Boffa JJ, et al. Autoimmune manifestations associated with lymphoma: Characteristics and outcome in a multicenter retrospective cohort study. Leuk. Lymphoma. 2018;59:1399-1405

3. Kleinstern G, Averbuch M, Abu Seir R, Perlman R, Ben Yehuda D, Paltiel O. Presence of autoimmune disease affects not only risk but also survival in patients with B-cell non-Hodgkin lymphoma. Hematol. Oncol. 2018;36:457-462.