Practice Patterns and Predictors of Severe Toxicity Among Older Adults with Diffuse Large B Cell Lymphoma Treated with Frontline Chemoimmunotherapy

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.1435-1435
• Main Authors: Ye, Star, Narkhede, Mayur, Bliven, Sean Patrick, Goyal, Gaurav, Mehta, Amitkumar, Harmon, Christian, Clark, Deanna, Ubersax, Clare, Rangarajan, Sunil, Williams, Grant R, Giri, Smith
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-151211

Introduction: Chemoimmunotherapy with R-CHOP is the standard of care for newly diagnosed diffuse large B cell lymphoma (DLBCL) leading to high cure rates although treatment-related toxicities are significant among older adults. Reduced dose R-CHOP has been proposed to balance efficacy and safety, but there is considerable ambiguity in “whom” and “by how much” with the best available data on those >80y [Peyrade et al 2011]. In this study, we sought to document the variability in chemotherapy dosing among unselected older adults with DLBCL treated with R-CHOP at a large, urban academic center in the Deep South. In addition, we sought to determine how baseline clinical features impacted tolerance of treatment. Methods: We conducted a single-institution retrospective review of all adults with newly diagnosed DLBCL initiating chemoimmunotherapy, predominantly R-CHOP, between 1/2015 and 2/2021 at the University of Alabama at Birmingham. For the current analysis, the cohort was limited to patients >70y. We extracted information on baseline clinico-demographic variables (age, sex, race, albumin, ECOG performance status [ECOG PS], Charlson comorbidity index [CCI], cancer type, stage, Revised International Prognostic Index score) and treatment intensity (type and dose of chemotherapy at 1 st cycle). Dose reduction was defined as any pre-planned reduction in cyclophosphamide, vincristine, or doxorubicin from standard CHOP dosing for cycle 1 of treatment. The primary outcome of interest was ≥grade 3 treatment-related toxicity (using CTCAE v5.0) occurring up to 30 days from the last dose of R-CHOP; secondary outcomes included dose modifications (dose delays >7d, dose reductions and treatment discontinuation) and health care utilization (unplanned emergency department visits and hospitalizations). Given high missingness for ECOG PS, we performed multiple imputation with chained equations producing 10 imputed datasets. Finally, we built a multivariate logistic regression model to identify baseline characteristics associated with severe toxicity; putative risk factors included age, sex, ECOG PS, CCI, albumin and treatment intensity. We pooled regression coefficients across imputed datasets using Rubin's rules. All hypothesis testing were two-sided, and the level of significance was chosen as 0.05. Results: Of 287 patients with DLBCL initiating R-CHOP during the study period, 101 (35%) patients were included in our cohort. The median age was 76y (IQR 73-79), with 55% males