Toxicity and Response Among Octogenarians and Nonagenarians with Diffuse Large B Cell Lymphoma Treated with Rituximab-CHOP Therapy

Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of lymphoma diagnosed in the United States. Majority of patients diagnosed with DLBCL are in their seventh decade at the time of presentation. Previous studies demonstrate that relative dose intensity (RDI) is an important prognostic factor for survival in patients with DLBCL. Elderly patients who receive chemotherapy intensity comparable to younger patients demonstrate similar outcomes. In our experience, elderly patients appear to receive lower doses of anthracycline based chemotherapy secondary to significant toxicity, poor performance status, or comorbid conditions. We present our experience of RCHOP chemotherapy in the treatment of DLBCL among octogenarians and nonagenarians.

The study population was selected using the Vanderbilt electronic medical record database. After obtaining IRB approval, 102 patients undergoing RCHOP therapy at a single institution between January 2000 and January 2010 were included in our analysis. Patients who were treated with RCHOP elsewhere were excluded from the study. Pre-treatment co-morbidities were identified and scored using the Cumulative Illness Rating Scale (CIRS). All data was compiled using Research Electronic Data Capture (REDCap). Descriptive statistics and multivariate logistic regression modeling were performed using SPSS software.

Of the 102 identified patients, 37 (36%) were aged 70 years or greater with a median age of 79 years (range 70–90). The median age of patients <70 years was 59 years (range 20–70). The majority had a diagnosis of DLBCL while eight (7.8%) patients had follicular grade 3b lymphoma. Differences in baseline BMI and body surface area (BSA) were statistically significant between age groups (70 years or greater: less than 70 years). All baseline laboratory data including absolute neutrophil count, absolute lymphocyte count, hemoglobin, blood albumin level, and LDH level were similar between groups. In addition, disease stage, International Prognostic Index (IPI), and age-adjusted IPI were not statistically different between the two age groups. Baseline comorbidities quantified with CIRS scoring showed that pts >70 had a higher average CIRS score (7.5 vs. 5.8, p <0.005), and a greater proportion had severe or not optimally controlled chronic baseline conditions (43% vs. 23 %, OR 2.5, p< 0.03). The two groups had a similar average number of chemotherapy cycles (5.8 vs. 5.7). The average chemotherapy dose intensity was lower in pts> 70 and experienced a greater frequency of dose reductions during treatment (73% vs. 18%, OR 12, p<0.001). The average relative dose intensity however remained greater than 70% of reference standard intensity in 32 of 37 aged patients (86%). Furthermore, only 4 of the aged patients (11%) received doxorubicin at an RDI < 10mg/m²/week. A complete response was observed in 92% of the patients and a difference was not observed between the two age groups (95% vs 91%). Frequency of neutropenia (grade 3–4) and febrile neutropenia was similar between age groups (43% vs. 45% for neutropenia, 22% vs. 17% febrile neutropenia). Prophylactic colony stimulating factors from the onset of RCHOP was more commonly administered among the elderly (92% vs. 28%, OR 29, p<0.001). Despite the use of early growth factors and dose reductions, the frequency of at least one hospitalization during chemotherapy was significantly higher among the octogenarians and nonagenarians (54% vs. 32%, OR 2.5, p<0.03). Multivariate logistic regression analysis was performed to identify age, BSA and comorbidity scoring as statistically significant predictors of any dose reduction after controlling for sex, LDH level, disease stage, performance status, and prophylactic G-CSF use.

Our study identifies age as a predictor of dose reduction in RCHOP used to treat patients with aggressive lymphoma. The RDI of anthracycline among the vast majority of patients was maintained at greater than 10mg/m²/week and may help explain the high frequency of complete response observed in both age groups. We conclude that patients over the age of 70 years can receive an attenuated dose of chemotherapy without compromising the response rates while experiencing similar toxicities. Additional studies with expanded population size and extended outcome data could help identify target RCHOP intensity for elderly patients with DLBCL.

No relevant conflicts of interest to declare.