key: cord-1003643-caximg9r
authors: Yamasaki, Satoshi; Matsushima, Takumi; Minami, Mariko; Kadowaki, Masanori; Takase, Ken; Iwasaki, Hiromi
title: Clinical impact of bendamustine exposure on lymphopenia risk after bendamustine and rituximab combination therapy for follicular lymphoma: a single-institute retrospective study
date: 2021-01-03
journal: Ann Hematol
DOI: 10.1007/s00277-020-04388-6
sha: 63c0a3965d5a254d9ebba5ad5ff55a767546b333
doc_id: 1003643
cord_uid: caximg9r

nan

Dear Editor: Bendamustine produces long-lasting objective responses in patients with indolent non-Hodgkin lymphoma, including follicular lymphoma (FL) [1] . However, lymphopenia, especially a reduced number of CD4-positive T cells, was reported to potentially lead to lethal infections after bendamustine therapy [2] . Employing bendamustine at cumulative doses ≥ 1080 mg/m 2 might induce delayed CD4-positive T cell recovery [3] . We investigated the effects of bendamustine exposure at cumulative doses < 1080 versus 1080 mg/m 2 on the reduction of CD4-positive T cell counts following bendamustine therapy in patients with FL. This was a retrospective analysis of data from 59 patients with FL who received bendamustine therapy from January 2011 to December 2018 in our institution. The study protocol was approved by the Kyushu Medical Center review board. According to the total dose and number of treatment cycles of bendamustine, we divided the patients into three groups: < 1080 mg/m 2 bendamustine for 4 cycles (group 1, n = 29), < 1080 mg/m 2 bendamustine for 6 cycles (group 2, n = 8), and 1080 mg/m 2 bendamustine for 6 cycles (group 3, n = 22). As presented in Table 1 , the mean age was higher in group 2 (p = 0.043), and the number of prior chemotherapy regimens was higher in group 1 (p = 0.039). Although the number of patients with CD4-positive T cell counts < 200/μl at baseline tended to be lowest in group 2 (p = 0.067), which was associated with age < 70 years (vs. ≥ 70; odds ratio [OR] = 8.520, 95% confidence interval [CI] = 2.030-35.80, p = 0.034) and 0-1 prior chemotherapy regimens (vs. > 1; OR = 5.160, 95% CI = 1.320-20.10, p = 0.018) using multivariate logistic regression analysis, the number of patients with CD4positive T cell counts < 200/μl after 3 months of bendamustine treatment also tended to be lowest in group 2, and this finding was not associated with any patient characteristics (Table 1) . Coronavirus disease 2019 (COVID-19) raises specific concerns in terms of morbidity and mortality for patients with FL because of their immunocompromised status induced by the disease or recent exposure to cytotoxic chemotherapy, especially b e n d a m u s t i n e a n d a n t i -C D 2 0 i m m u n o t h e r a p y . Bendamustine appeared to be associated with death, but most patients treated with bendamustine had relapsed/refractory lymphoma [4] . Anti-CD20 treatment within 1 year was not associated with death. Further studies are m erited t o explore t he impact of bendamustine on the evolution of COVID-19. Because the standard dose of bendamustine therapy may be associated with a high mortality risk, our data suggest that for elderly patients receiving bendamustine-based therapy, a reduced initial bendamustine dose (70 mg/m 2 ) such as that used in the GREEN study for unfit patients with chronic lymphocytic leukemia at the investigator's d i s c r e t i o n [ 5 ] , o p p o s e d r e d u c e d n u m b e r s o f chemoimmunotherapy cycles, might explain the decreased risk of serious infections in this population. This study had several limitations, including its singleinstitute nature and small sample size. Further evaluations for FL are warranted to identify the best dose of bendamustine, notably a reduced initial bendamustine dose, and suitable patients to define the best-tailored treatment at diagnosis. 

Conflict of interest The authors declare that they have no competing interests. WBC, white blood cell; CD, cluster of differentiation; IgG, immunoglobulin G Continuous variables were expressed as the median and range, and differences between groups were assessed using the Mann-Whitney U test. Intergroup differences in categorical variables were expressed as numbers and percentages, and differences between groups were assessed using the chi-squared test

Study group indolent Lymphomas (StiL) (2013) Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised

Bendamustine associated immune suppression and infections during therapy of hematological malignancies

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

Determinants of outcome in Covid-19 hospitalized patients with lymphoma: a retrospective multicentric cohort study

Obinutuzumab plus bendamustine in previously untreated patients with CLL: a subgroup analysis of the GREEN study

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Acknowledgments We thank the patients and clinical staff for their participation in the study. We also acknowledge the Clinical Research Institute, Kyushu Medical Hospital, for editorial support. We thank Joe Barber Jr., PhD, from Edanz Group (https://en-author-services.edanz. com/ac) for editing a draft of this manuscript.

Ethics approval This was a retrospective study with no experimental interventions. The study was approved by the Institutional Review Board of the Kyushu Medical Center in Japan.