Abstract
Background: Mantle Cell Lymphoma (MCL) is an incurable subtype of non-Hodgkin lymphoma with a median age of 68 yrs at diagnosis. While clinical trials have historically divided patients with MCL by eligibility for autologous stem cell transplantation, this fails to capture the heterogeneity among elderly patients, particularly those > 75 years. This large retrospective cohort study, using data from the Flatiron Health analysis aims to describe patient characteristics, treatment patterns, and clinical outcomes (real-world overall survival [OS], time to next treatment [TTNT]) in elderly patients with MCL, and compare these with their younger counterparts.
Methods: This study utilized the Flatiron Health Research Database.We included patients with MCL diagnosed and treated from from 1/1/2011 to 2/21/25 (n = 6893). Patients <18 yrs and those with missing demographics or survival data were excluded (n=10). The remaining 6883 patients were divided into age groups - <65(younger), 65-75, and >75 yrs. Descriptive statistics were used to summarize patient and disease characteristics as well as treatment patterns. Time-to-event outcomes were estimated using the Kaplan-Meier method and presented with their respective two-sided 95% confidence intervals (CIs). Real-world time to next treatment (TTNT) and overall survival (OS) were estimated with Kaplan Meier curves and compared cross age groups using the log-rank test. Multivariate Cox Proportional-Hazards Models were fitted to adjust for potential cofounding variables such as sex, race and performance status (ECOG). Hazard ratios (HR), 95% confidence intervals and p-values were reported.
Results: Among the total cohort, mean age at diagnosis was 68 with 2287 (33.2%) diagnosed <65 years of age, 2681 (39%) between 65-75 and 1915 (27.8%) >75 years. Compared to patients <65, those >75 were more likely to be female (33.3% versus 26.1%) and have worse functional status (ECOG =>2) (13.1% versus 3.3%), while they were less likely to be Black/African American (2.9% versus 4.5%). Patients > 75 were less likely to be tested for TP53 mutation (86.3% not tested) and deletion (35.1% not tested). Elderly patients were noted to have lower albumin (p<0.001), higher creatinine (p<0.001) and lower BUN (p<0.001) at baseline. Median overall survival varied across age groups: for younger patients, the median OS was 139.3 months (123 months -NR), between 65-75 years, median OS 81.2 months (77.5-87 months) and elderly patients >75 yrs of age 40.3 months (36.8-43.9months). In a multivariate cox regression (MVA) within patients >75, we found that ECOG >=2 (HR 1.98[1.52-2.58]), and elevated white blood cell counts (HR 1.73[1.38-2.15]), LDH (HR 1.10[1.07-1.14]) creatinine (HR 1.25[1.04-1.51]) and calcium (HR 1.17[1.01-1.35]) levels were associated with worse survival. Conversely, African American race (HR 0.56 [0-35-0.90]) and higher albumin values (HR 0.57 [0.47-0.68]) were associated with improved survival.More elderly patients with MCL (10.9%, n=208) received anti-CD20 monotherapy in the first line setting, and younger patients received more chemotherapy with or without immunotherapy (71.5%,n =1636, p<0.001). OS significantly differed across age groups after first line of therapy, noting a median OS of 126.1m (116.2-141.2 months) for younger, 75.6 m(70.9-79.7m) for ages 65-75, and 36.7 months (33.3-39.3 m) for elderly patients. TTNT for these age groups was 23.7m (9.4-33.5m), 13.5m (10.2-23.8m) and 12.5 m (10.3-16.2m) respectively. 16.7% (n=320) of elderly patients did not receive any treatment in the frontline setting. In those receiving BTK (with or without chemotherapy), the median OS and TTNT for patients <65 was 122.7m(110.9-137.1m) and 23.7m (9.4-33.5m), compared to >75yrs with 38.9m (35.3-42.8m) and 12.5 m(10.3-16.2m) respectively. Patients >75 receiving chemotherapy alone (median OS 38.9m (35.3-42.8m) lived significantly longer than those in the BTK (with or without chemotherapy) group (median OS 25.2m (20.2-34.8m) and had a longer TTNT (median TTNT 20.3m (17.5-22.5m) versus 12.5m (10.4-16.2m) respectively).
Conclusions: In this large real-world analysis of elderly patients with MCL using the Flatiron Health database, we found poor outcomes for patients >75, particularly those treated with BTK inhibitors. We also identified key prognostic factors in a MVA among elderly patients, including race, ECOG, albumin, creatinine, LDH and WBC count.
