Patterns of Chemotherapy/Immunotherapy and Survival in Mantle Cell Lymphoma: Evidence from SEER-Medicare
Authors: Griffiths Robert , Danese Mark , Gleeson Michelle , Knopf Kevin 
Published: April 2020

Abstract
Introduction: Mantle cell lymphoma (MCL) is a relatively rare form of non-Hodgkin’s lymphoma (NHL) comprising approximately 6% of all new NHL cases.
Methods: Using the National Cancer Institute’s SEER registry linked to Medicare claims, we identified 503 patients with MCL (histology code 9673) as their first malignancy between January 1, 1999 and December 31, 2002. Patients were followed until the development of a second primary cancer, transition to an HMO, the end of their claims history (December 31, 2005), or death. Medicare claims were used to identify and classify chemotherapy and/or immunotherapy (C/I) regimens as well as to identify radiation therapy. The initial C/I treatment approach (no treatment, chemotherapy only, and immunotherapy with or without chemotherapy) was based on the first 90 days after diagnosis. The specific regimen was identified using the 30 day period after the initial C/I administration. Multivariate Cox proportional hazards analyses were performed to identify patient socio-demographic and clinical factors associated both with time to treatment initiation and with survival. Potential risk factors in the models included age, gender, race, stage, comorbidity burden*, year of diagnosis, education, rural/urban status, poverty indicators, nodal involvement, anemia*, neutropenia*, and thrombocytopenia* (*=based on diagnosis codes).
Results: Median age was 76 years, 65% were male, 11% were non-white, and 57% were diagnosed with Stage IV disease. Overall, 81% (n=405) received C/I of whom 30% (n=123) received radiation at any time during follow up. The median time to first C/I was 51 (95% CI 46–56) days. Among patients receiving C/I, 138 received rituximab with or without CHOP or CVP, 101 received either CHOP or CVP alone, 96 could not be clearly classified into these groups, and 70 did not have identifiable C/I agents in the data (only administration codes were present). In multivariate analysis of time to initiating C/I, patients age ≥ 80 years were 46% less likely to initiate C/I (compared to age 66–70), those with advanced disease (Stage III or IV) were 41% (Stage III) or 59% (Stage IV) more likely to initiate C/I (compared to Stage I), and those with anemia were 49% more likely to initiate C/I (p&lt;0.05 for all). Unadjusted median survival for the cohort was 29 (95% CI 26–31) months. Unadjusted median survival was 20 (95% CI 12–30) months in patients untreated with either chemo- or immunotherapy, 28 (95% CI 24–31) months in patients treated with chemotherapy only, and 33 (95% CI 28–39) months in patients treated with immunotherapy (with or without chemotherapy). In multivariate survival analysis, compared to no C/I treatment, immunotherapy with or without chemotherapy was associated with 44% lower risk of death (95% CI 23% to 60%), while chemotherapy alone was not significantly different. Other factors significantly associated with mortality included increasing age, increasing stage, and diagnosis of anemia.
Conclusion: Findings indicate the majority of patients in this elderly population received C/I within the first 2 months following diagnosis. Immunotherapy, but not chemotherapy alone, was associated with improved survival. However, because these are observational data, even with extensive adjustment, the possibility of residual confounding should be kept in mind.