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

Abstract

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.