ベンダムスチン(Bendamstine)投与時にリスクとなる感染症について

Increased Risk of Infectious Complications in Older Patients With Indolent Non-Hodgkin Lymphoma Exposed to Bendamustine.
Clin Infect Dis. 2019 Jan 7;68(2):247-255. doi: 10.1093/cid/ciy458.

論文読む上での基礎情報

ベンダムスチン Bendamstineの有害事象として骨髄抑制がよくみられる.
特にCD4陽性細胞のリンパ球現象はベンダムスチン投与後によくみられる.
iNHLに対するベンダムスチンの臨床試験ではGrade3~4のリンパ球減少は最大74%の患者に生じている.
R-CHOPよりBR療法の方が感染症が少ないという臨床試験がある.(Lancet Oncol 2016; 17:57–66.)

Clinical question

iNHLにBRするとCMVとPCPがどれくらいリスクとして
R-CHOPと増えるんだろうか.

Key point

BR療法は他のレジメンと比べて
細菌性肺炎,CMV,VZVなどの感染症がやはり増加する.
予防によって以下のぐらい防げると筆者らは予想しているらしい.

*** [x] 筆者らは予防投与によって
70人予防して1人の細菌感染症
374人予防して1人のPCP
269人予防して1人のCMV
582人予防して1人とヒストプラズマ症
を防げるとしている.**

We estimate that 1 bacterial infection per 70 patients, 1 PCP case per 374 patients, 1 CMV case per 269 patients, 1 VZV case per 23 patients, and 1 histoplasmosis case per 582 patients with iNHL treated with bendamustine-containing chemotherapy could be prevented with prophylaxis.

Abstract

背景

ベンダムスチン(Bendamstine:トレアキシン®️)は、indolent 非ホジキンリンパ腫(iNHL)の治療に使用されている化学療法薬である.
化学療法は効果的ではあるが、重篤なT細胞リンパ球減少症を引き起こし、それは感染の危険性を高めるだろう.
iNHLの高齢患者におけるベンダムスチン含有レジメンに関連する感染性合併症について検討した.

Bendamustine is a potent chemotherapy agent increasingly used to treat indolent non-Hodgkin lymphoma (iNHL). While effective, it causes significant T-cell lymphopenia, which may increase risk of infection. We examined infectious complications associated with bendamustine-containing regimens among older patients with iNHL.

方法

SSER(SEER: Surveillance, Epidemiology, and End Results ) – 臨床コホート研究のために、2006年から2013年の間に化学療法を受けたiNHL(濾胞性リンパ腫、MZL、原発性マクログロブリン血症:
follicular, marginal zone, Waldenström macroglobulinemia)患者9395人を特定した.
そのうち13%がベンダムスチン含有レジメンを受けた.
ベンダムスチンの有無で治療を受けた患者のベースライン特性と感染発生率を比較した.
ベンダムスチンに関連する感染リスクを決定するために、多変量Cox比例ハザード回帰を用いて人口統計、併存症、疾患および治療特性、感染の危険因子、および抗菌薬の予防について検討を行った.

For this Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort study, we identified 9395 patients with iNHL (follicular, marginal zone, Waldenström macroglobulinemia) treated with chemotherapy from 2006 to 2013. Thirteen percent received bendamustine-containing regimens. We compared baseline characteristics and infection incidence rates between patients treated with and without bendamustine. We conducted multivariate Cox proportional hazards regression (adjusting for demographics, comorbidities, disease and treatment characteristics, risk factors for infection, and antimicrobial prophylaxis) to determine infectious risks associated with bendamustine.

結果

ベンダムスチンは、一般的な感染症および日和見感染症を増加させた.(内訳は下記)
細菌性肺炎(hazard ratio [HR], 1.50 [95% confidence interval {CI}, 1.21-4.85])
サイトメガロウイルス (HR, 3.98 [95% CI, 1.40-11.26])
水痘帯状疱疹ウイルス(HR、1.49 [95%CI、1.18-1.89])
ヒストプラスマ症(HR、3.55 [95%CI、1.10-11.42])、
ニューモシスチス肺炎 PCP:(第三選択療法:HR, 3.32 [95% CI, 1.00-11.11])

感染のリスクは3コース目以降のレジメンとしてベンダムスチンを投与されている患者でより顕著で,好中球減少症やステロイドの投与などの要因と独立して関連していた.

Bendamustine was associated with an increased risk of both common infections such as bacterial pneumonia (hazard ratio [HR], 1.50 [95% confidence interval {CI}, 1.21-4.85]) and opportunistic infections such as cytomegalovirus (HR, 3.98 [95% CI, 1.40-11.26]), varicella zoster virus (HR, 1.49 [95% CI, 1.18-1.89]), histoplasmosis (HR, 3.55 [95% CI, 1.10-11.42]), and Pneumocystis jirovecii pneumonia (when administered as third-line therapy: HR, 3.32 [95% CI, 1.00-11.11]). Risk of infections was more prominent in patients receiving bendamustine as part of later (third-line and above) regimens, and independently associated with well-established factors such as neutropenia and corticosteroid exposure.

まとめ

ベンダムスチンは、iNHL患者における細菌感染症および日和見感染症のリスク増加と関連している.
これらの患者には、抗菌薬予防の潜在的役割についてのさらなる前向き調査が必要である.

Bendamustine is associated with an increased risk of common and opportunistic infections in patients with iNHL. Further prospective investigation into the potential role of antimicrobial prophylaxis is needed in these patients.

Table and Figure


原文

Abstract
BACKGROUND:
Bendamustine is a potent chemotherapy agent increasingly used to treat indolent non-Hodgkin lymphoma (iNHL). While effective, it causes significant T-cell lymphopenia, which may increase risk of infection. We examined infectious complications associated with bendamustine-containing regimens among older patients with iNHL.
METHODS:
For this Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort study, we identified 9395 patients with iNHL (follicular, marginal zone, Waldenström macroglobulinemia) treated with chemotherapy from 2006 to 2013. Thirteen percent received bendamustine-containing regimens. We compared baseline characteristics and infection incidence rates between patients treated with and without bendamustine. We conducted multivariate Cox proportional hazards regression (adjusting for demographics, comorbidities, disease and treatment characteristics, risk factors for infection, and antimicrobial prophylaxis) to determine infectious risks associated with bendamustine.
RESULTS:
Bendamustine was associated with an increased risk of both common infections such as bacterial pneumonia (hazard ratio [HR], 1.50 [95% confidence interval {CI}, 1.21-4.85]) and opportunistic infections such as cytomegalovirus (HR, 3.98 [95% CI, 1.40-11.26]), varicella zoster virus (HR, 1.49 [95% CI, 1.18-1.89]), histoplasmosis (HR, 3.55 [95% CI, 1.10-11.42]), and Pneumocystis jirovecii pneumonia (when administered as third-line therapy: HR, 3.32 [95% CI, 1.00-11.11]). Risk of infections was more prominent in patients receiving bendamustine as part of later (third-line and above) regimens, and independently associated with well-established factors such as neutropenia and corticosteroid exposure.
CONCLUSIONS:
Bendamustine is associated with an increased risk of common and opportunistic infections in patients with iNHL. Further prospective investigation into the potential role of antimicrobial prophylaxis is needed in these patients.

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