Ibrutinib as first-line therapy for mantle cell lymphoma: a multicenter, real-world UK study.

ABSTRACT: During the COVID-19 pandemic, ibrutinib with or without rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. Because limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib with or without rituximab for untreated MCL were evaluated for treatment toxicity, response, and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 ≥ 30%). A total of 149 patients from 43 participating centers were enrolled: 74.1% male, median age 75 years, 75.2% Eastern Cooperative Oncology Group status of 0 to 1, 36.2% high-risk, and 8.9% autologous transplant candidates. All patients received ≥1 cycle ibrutinib (median, 8 cycles), 39.0% with rituximab. Grade ≥3 toxicity occurred in 20.3%, and 33.8% required dose reductions/delays. At 15.6-month median follow-up, 41.6% discontinued ibrutinib, 8.1% due to toxicity. Of 104 response-assessed patients, overall (ORR) and complete response (CR) rates were 71.2% and 20.2%, respectively. ORR was 77.3% (low risk) vs 59.0% (high risk) (P = .05) and 78.7% (ibrutinib-rituximab) vs 64.9% (ibrutinib; P = .13). Median progression-free survival (PFS) was 26.0 months (all patients); 13.7 months (high risk) vs not reached (NR) (low risk; hazard ratio [HR], 2.19; P = .004). Median overall survival was NR (all); 14.8 months (high risk) vs NR (low risk; HR, 2.36; P = .005). Median post-ibrutinib survival was 1.4 months, longer in 41.9% patients receiving subsequent treatment (median, 8.6 vs 0.6 months; HR, 0.36; P = .002). Ibrutinib with or without rituximab was effective and well tolerated as first-line treatment of MCL, including older and transplant-ineligible patients. PFS and OS were significantly inferior in one-third of patients with high-risk disease and those unsuitable for post-ibrutinib treatment, highlighting the need for novel approaches in these groups.

Kinetics of T-cell subset reconstitution following treatment with bendamustine and rituximab for low-grade lymphoproliferative disease: a population-based analysis.

Delayed lymphocyte and T-cell immune reconstitution following bendamustine-rituximab (BR) for indolent non-Hodgkin lymphoma (iNHL) has been described, but no information is available for chronic lymphocytic leukaemia (CLL). We present a population-based retrospective analysis of immune reconstitution and risk of infection following BR. Outcomes included timing/correlates of CD4+ recovery and risk of ≥grade 3 infections. Consecutively treated patients (1 April 2014 to 31 January 2017) were included (n = 295),with a median age of 65 years (range 33-92); 57% were 1st line treatments. Median cumulative bendamustine dose was 1080 mg/m2 (range 140-1440 mg/m2 ). CD4/CD8/CD19/NK subsets were available for 148 patients. Median follow-up was 24 months. Median times to lymphocyte count (ALC) recovery (≥1 × 109 /l) and CD4+ recovery (≥0·2 × 109 /l) were 26 and 24 months, respectively. Bendamustine total dose >1080 mg/m2 (hazard ratio [HR] 0·4; 95% confidence interval [CI]: 0·2-0·8), end-of-treatment ALC ≤0·4 × 109 /l (HR 0·53; 95% CI: 0·3-0·9) and CD4+ <0·1 × 109 /l 1-year post-BR (HR 0·03; 95% CI: 0·008-0·15) were covariables for delayed CD4+ recovery. ALC-recovery ≥1 × 109 /l was an unreliable predictor of CD4+ recovery (negative predictive vale 74%, positive predictive value 86%, likelihood ratio 3·3). CD4+ lymphopenia >3 years was a significant risk factor for ≥grade 3 infections (Odds ratio 3·4; 95% CI: 1·4-6·9). CD4+ recovery after BR is unexpectedly delayed and late recovery is associated with risk of serious infections. Monitoring CD4+ following BR could identify patients at high risk of delayed infections.