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

Abstract

Summary 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.

Chronic lymphocytic leukaemia: the role of T cells in a B cell disease

“…In this study, there was a high rate of major infections requiring hospitalisation (49%), and this was associated with the delayed recovery of CD4 T cell counts (Martínez‐Calle et al , ). Neither fludarabine or bendamustine appear to affect natural killer (NK) cell numbers (Ysebaert et al , ; Martínez‐Calle et al , ).…”

“…Bendamustine is used as a chemotherapy alternative for CLL patients unsuitable for fludarabine combinations and is often used in combination with rituximab. Patients treated with this regimen for more than 36 months demonstrated similar effects on T cell counts to fludarabine‐based regimens, with CD4 T cells being disproportionately affected and slower to recover back to normal numbers (Martínez‐Calle et al , ). In this study, there was a high rate of major infections requiring hospitalisation (49%), and this was associated with the delayed recovery of CD4 T cell counts (Martínez‐Calle et al , ).…”

“…Patients treated with this regimen for more than 36 months demonstrated similar effects on T cell counts to fludarabine‐based regimens, with CD4 T cells being disproportionately affected and slower to recover back to normal numbers (Martínez‐Calle et al , ). In this study, there was a high rate of major infections requiring hospitalisation (49%), and this was associated with the delayed recovery of CD4 T cell counts (Martínez‐Calle et al , ). Neither fludarabine or bendamustine appear to affect natural killer (NK) cell numbers (Ysebaert et al , ; Martínez‐Calle et al , ).…”

Does rehabilitation pose a risk to patients suffering from haemato‐oncological diseases? Results of a monocentric, retrospective analysis in Germany

“…In patients who have been treated with immunochemotherapy or high-dose chemotherapy with autologous stem cell transplantation (HDC/autoSCT), an immune deficiency is expected for several months (Aksoy, Dizdar, Hayran, & Harputluoǧlu, 2009;Aksoy et al, 2007;Martínez-Calle et al, 2019;Steingrimsdottir, Gruber, Bjorkholm, Svensson, & Hansson, 2000).…”

Author reply

“…For younger patients, with an anticipated median PFS beyond 15 years after anti‐CD20 antibody‐bendamustine chemotherapy, we can anticipate for most patients any CD4 lymphopenia will have resolved at the time of any relapse . Martinez‐Calle reported a median time to lymphocyte count recovery (≥1 × 10 9 /L) following bendamustine of 26 months with rituximab maintenance associated with further delays in recovery . Saito observed recovery of lymphocyte and CD4‐positive T‐cell counts to those at baseline at 7–9 months after the completion of bendamustine .…”