Exploring the potential cost-effectiveness of precision medicine treatment strategies for diffuse large B-cell lymphoma

Abstract

Activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) is associated with worse survival after standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) chemoimmunotherapy compared to germinal center B-cell-like (GCB) subtype. Preliminary evidence suggests that benefits from novel agents may vary by subtype. Hypothesizing that treatment stratified by DLBCL subtype could be potentially cost-effective, we developed micro-simulation models to compare three first-line treatment strategies: (1) standard RCHOP for all patients (2) subtype testing followed by RCHOP for GCB and novel treatment for ABC DLBCL, and (3) novel treatment for all patients. Based on phase 2 evidence, we used lenalidomide + RCHOP as a surrogate novel treatment. The subtype-based approach showed a favorable incremental cost-effectiveness ratio of $15,015/quality-adjusted life year compared with RCHOP. Although our exploratory analyses demonstrated a wide range of conditions where subtype-based treatment remained cost-effective, data from phase 3 trials are needed to validate our models' findings and draw definitive conclusions.

Keywords: ABC DLBCL; Lymphoma; cost-effectiveness; diffuse large B-cell lymphoma; subtype testing.

Figure 1. Subtype-based treatment strategy allows misclassification of germinal center B-cell-like (GCB)/activated B-cell-like (ABC) subtype due to imperfect testing by immunohistochemistry

Treatment selection is guided by the subtype identified by the test, whereas survival is determined by the true subtype for a given treatment.

Figure 2. Cost-effectiveness acceptability curves at various survival benefit levels for germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes

Subtype-based treatment is based on gene expression profiling (GEP) assay. (A) Minimal survival improvement for both subtypes by novel treatment, (B) modest survival improvement only for ABC subtype by novel treatment, (C) modest survival improvement for both subtypes by novel treatment.