Brentuximab vedotin and dose attenuated chemoimmunotherapy for patients 75 years and older with diffuse large B-cell lymphoma with analysis of outcomes by frailty.

INTRODUCTION: Dose attenuated rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-miniCHOP) is a curative-intent regimen that balances safety and efficacy in older patients with diffuse large B-cell lymphoma (DLBCL). Incorporation of targeted agents into this backbone and the use of geriatric assessments (GA) are research priorities. Brentuximab vedotin (BV) is an anti-CD30 antibody drug conjugate that is active in DLBCL and has been safely combined with chemoimmunotherapy in younger patients. We conducted a feasibility study of BV in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-miniCHP), integrating GA and frailty assessment to describe the physiologic health of the cohort.

MATERIALS AND METHODS: Patients aged 75 years and older with DLBCL were treated with six cycles of BV and R-miniCHP. All patients underwent GA at screening, following prephase and at the end of treatment. Frailty was determined using the Deficit Accumulation Frailty Index (DAFI) using clinical and GA variables. The primary feasibility endpoint was the treatment completion rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and complete response (CR). Exploratory endpoints included PFS, OS, ORR, and CR by CD30 status, and PFS and OS by DAFI score.

RESULTS: We enrolled 22 patients with a median age of 77.5 years (range 75-91). Seventeen patients (77.3%) completed six cycles of BV-R-miniCHP. The ORR was 85.7% (71.4% CR). With a median follow up of 4.3 years, the median PFS was not reached and the two-year PFS was 63.6% (90% CI = 44.3%, 77.8%). There was no difference in response, or survival by CD30 status. All 22 patients completed components of the baseline GA. There was no difference in two-year PFS (non-frail 50.0% (90% CI =23.0%, 72.1%) vs prefrail/frail 75.0% (90% CI = 47.4%, 89.5%), p = 0.49) or OS (non-frail 50.0% (90% CI = 23.0%, 72.1%) vs prefrail/frail 83.3% (90% CI =55.7%, 94.5%), p = 0.22) based on frailty as measured by DAFI score. Hematologic toxicities and infections were the most common grade ≥ 3 adverse events. Ten patients (45%) reported a total of 16 serious adverse events. There were two deaths during treatment.

DISCUSSION: Incorporation of GA and BV R-miniCHP is feasible in untreated, older adults with DLBCL.