Final analysis of Australasian Leukaemia & Lymphoma Group NHL29: A phase II study of ibrutinib, rituximab and mini‐CHOP in very elderly patients with newly diagnosed DLBCL

Abstract

Introduction: The optimal treatment for very elderly patients (pts) with newly diagnosed Diffuse Large B Cell Lymphoma (DLBCL) remains controversial. R-mini-CHOP is an established standard of care in elderly patients with DLBCL, with a 2 yr OS of 59% and PFS of 47% (Peyrade et al., Lancet Oncol 2011). We present our final data from this prospective Phase II study of ibrutinib, rituximab and mini-CHOP in pts ≥75 yrs with newly diagnosed DLBCL. Methods: Pts received six 21-day cycles of ibrutinib 560 mg daily and R-mini-CHOP (Rituximab 375 mg/m2, cyclophosphamide 400 mg/m2, doxorubicin 25 mg/m2, vincristine 1 mg on day 1 & prednisone 40 mg/m2 or 100 mg/d × 5) followed by an additional two 21 day cycles of rituximab + ibrutinib (or high dose methotrexate for CNS prophylaxis). Primary endpoints were deliverability and 2 year overall survival (OS). Sample size calculations were made using a one-sample two-sided approach to detect a 15% improvement on the fixed Peyrade reference OS (59%) and PFS (47%) rates. Results: Eighty pts were recruited from Nov 2015 to Nov 2018. One died prior to receiving treatment and is not included in the analysis. Median age was 82 yrs (75–95); 81% stage III/IV; 54% age adjusted IPI 2–3. With a median follow-up of 35.5 months (m) (0.2, 71.7) (data cut 6 September 2022), there was a non-significant trend towards improvement in 2-year OS of 68% (55.6%, 77.4%) compared to the reference Peyrade cohort of 59% (p = 0.11). Median OS was 72 m (95% CI 35 m to not reached (NR)). Median 2-year PFS of 60.0% (47.7%, 70.3%) was significantly improved compared to the reference cohort of 47% (p = 0.03), with a median PFS of 40 m (95% CI 20.41, NR). Overall response assessment assessed by investigators at the end of treatment was 76% (61/80 pts), with a complete response rate of 70% (56/80 pts). All 6 cycles of R-mini-CHOP were completed in 63/79 pts (80%) and 57/79 pts (71%) completed all 8 cycles of therapy. The median Average Relative Total Dose and Average Relative Dose Intensity for the entire regimen was 97% (IQR 82, 100; 88, 100). 34/79 pts (43%) have died, 17 due to progressive disease and 5 were treatment-related. 67% pts experienced an SAE. Most common AEs were infections and diarrhoea (majority grade 1–2). In the EORTC QLQ-C30 there was an improvement in functional and symptom scales and on the EQ-5D-5L survey, there was a significant improvement in the median health state classification score and median visual analogue scale thermometer score over time. Encore Abstract - previously submitted to EHA 2023 The research was funded by: Janssen-Cilag Pty Ltd. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies Conflicts of interests pertinent to the abstract. E. Verner Research funding: Janssen-Cilag Pty Ltd. E. Hawkes Consultant or advisory role: Janssen-Cilag Pty Ltd. T. Cochrane Consultant or advisory role: Janssen Cilag Pty Ltd. C. Y. Cheah Consultant or advisory role: Janssen-Cilag Pty Ltd. Honoraria: Janssen-Cilag Pty Ltd. M. K. Gandhi Research funding: Janssen-Cilag Pty Ltd. B. E. Butcher Other remuneration: Janssen Cilag Pty Ltd. J. Trotman Research funding: Janssen-Cilag Pty Ltd.