IBRUTINIB AND RITUXIMAB AS FIRST LINE THERAPY FOR MANTLE CELL LYMPHOMA: UPDATED OUTCOMES FROM A MULTICENTRE, REAL-WORLD UK STUDY.
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All Authors
Shotton, R.
Tivey, A.
Eyre, T.
Lewis, D.
Allchin, R.
Walter, H.
Miall, F.
Zhao, R.
Santarsieri, A.
Mcculloch, R.
LTHT Author
Reeve, Miriam
LTHT Department
Medicines Management & Pharmacy Services
Contributor Profession (Non Medical)
Pharmacist
Publication Date
2023
Item Type
Conference Abstract
Language
Subject
Subject Headings
Abstract
Background: Ibrutinib (IBR) is an oral covalent Bruton's kinase inhibitor licensed for treatment of patients (pts) with relapsed/refractory mantle cell lymphoma (MCL). During the Covid-19 pandemic, IBR +/-rituximab (R) was approved by NHS England for 1st line treatment of MCL as a potentially safer alternative to immunochemotherapy. Limited data are available on the outcomes of ibrutinib-treated pts in the 1st-line setting. Aim(s): We previously reported outcomes for 66 pts treated under this scheme (EHA 2022, P1141). Here we report data for a larger cohort (n=149) with longer follow-up. Method(s): Adults commencing IBR +/-R for untreated MCL under interim Covid-19 arrangements were identified from 43 participating NHS centres in England; data were extracted from hospital records. High-risk disease features were defined as >=1 of TP53 mutation/deletion, blastoid/pleomorphic variant MCL, or Ki67%/MiB-1 >=30%. Overall and complete radiological response rates (ORR/CR) were assessed per local investigator according to the Lugano classification using CT and/or PET-CT. Survival analysis was performed using the Kaplan Meier method. Result(s): 149 pts were enrolled; 74.1% male, median age 75 years (41-94; 10.9% <65), 65.7% stage 4, 34.9% high-risk. 7.8% were considered fit for autologous stem cell transplant (ASCT). Simplified MCL International Prognostic Index (sMIPI) was 0-3 in 13.3%, 4-5 in 36.3% and >=6 in 50.4%. At median follow-up 15.6 months (m), pts received median 8 (1-33) 28-day IBR cycles. IBR was given with R in 55/141 (39.0%) pts. Starting dose was 560mg in 92.0%. Dose reductions/delays were noted in 33.8%. of 104 pts who underwent assessment of best response, ORR and CR was 71.2% and 20.2% respectively at a median of 4.9m. for pts with/without high-risk features, ORR was 60.5% vs 77.3% (p=0.069) and CR was 21.1% vs 19.7%. for pts with sMIPI >=6 vs 0-5, ORR was 66.7% vs 75.0% and CR was 23.5% vs 17.3%. for IBR given with/without R, ORR was 78.7% vs 64.9% and CR was 27.7% vs 14.0% (p=0.085). Median PFS for the whole cohort was 26.0m (18.8-33.2). Median OS was not reached (NR). Median PFS and OS were significantly lower in pts with high-risk features; PFS 9.7m (2.2 - 17.2) vs not reached (NR), p=0.002; OS 14.4m (10.2-18.6) vs NR, p=0.001 (Fig 1). Grade >=3 any-cause toxicity was reported in 27/133 pts (20.3%), including infection in 7.4%, myelosuppression and bleeding in 4.0% each, and 2 cases of stroke. New onset atrial fibrillation (AF) occurred in 9/126 pts (6.6%; median age 80 (58-94), of which 6 had a history of hypertension or coronary artery stenosis. 62/149 pts (41.6%) discontinued IBR due to progressive disease (PD) (53.2%), toxicity (19.4%), death (12.9%), patient choice (1.6%) and other/unknown reasons (12.9%). 44/149 pts (29.5%) died, due to MCL (n=31, 70.5%), infection (n=6, 13.6%), cardio/cerebrovascular disease (n=5, 11.4%), suicide and unknown cause (both n=1, 2.3%). 26 pts (19.7%) received second-line therapy; ORR and CR were 41.2% and 35.3% respectively. No pts underwent ASCT. Summary/Conclusion: In this real-world study of mostly transplant ineligible MCL pts, first line IBR +/-R was well tolerated and effective, especially in pts with low risk disease. ORR/CR were lower than reported in recent phase II studies (Gine et al 2022, Jain et al 2022), mainly due to inferior outcomes in pts with high-risk disease and impaired performance status, low use of R during the Covid-19 pandemic, and common use of CT for response assessment. Inferior outcomes noted in high-risk pts suggests that novel approaches should be considered in those with aggressive MCL biology.
Journal
HemaSphere