Background

Interstitial pneumonitis (IP), a fatal complication of DLBCL treatment, can bring great challenges to clinicians. We retrospectively investigated clinical characteristics and risk factors of previous IP patients, and analyzed their survival data.

Methods

556 DLBCL patients receiving CHOP-like regimens were enrolled between 2013 and 2018 in Sichuan Cancer Hospital.

Findings

The IP incidences were 4.9 % (27/556), 1.1 % (2/186), 5.2 % (10/191) and 8.4 % (15/179) in CHOP, R−CHOP and R-CDOP groups respectively (P = 0.005). When IP was diagnosed, monocyte and IL-6 were significantly higher while CD4 and CD4/CD8 significantly lower compared to baseline. 81.5 % (22/27) of IP patients were pathogen-negative with good response to glucocorticoid monotherapy. Only one patient died while the others recovered from IP and subsequently underwent previous chemotherapy. 19.2 % (5/26) of IP patients experienced IP recurrence, likely due to the reason of lower initial dose or faster withdrawal speed of glucocorticoid. Multivariate analysis identified male, in addition to G-CSF, rituximab and pegylated liposomal doxorubicin as risk factors. The 3-year PFS and OS were 74.1 % and 46.9 % respectively for patients with IP.

Interpretation

We suggest that IL-6, monocyte and CD4 should be monitored closely, especially in R−CHOP/R-CDOP group. Sufficient initial dose and slow decrease of glucocorticoid based on radiographic remissions were critical strategies to reduce IP recurrence. We speculate that drug-induced immune imbalance could be trigger of developing IP, causing a lower intensity cytokine storm, resulting in a potential immunotherapy. This complication might bring benefit in patients’ survival through a mechanism similar to PD-1.

中文翻译：

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并非全是坏事：DLBCL 患者的药物性间质性肺炎可能是致命的，但可能与更好的生存率有关

背景

间质性肺炎（IP）是DLBCL治疗的致命并发症，会给临床医生带来巨大挑战。我们回顾性调查了既往 IP 患者的临床特征和危险因素，并分析了他们的生存数据。

方法

四川省肿瘤医院于 2013 年至 2018 年间招募了 556 名接受 CHOP 样方案的 DLBCL 患者。

发现

CHOP、R-CHOP 和 R-CDOP 组的 IP 发生率分别为 4.9 % (27/556)、1.1 % (2/186)、5.2 % (10/191) 和 8.4 % (15/179) (P = 0.005)。当诊断出 IP 时，与基线相比，单核细胞和 IL-6 显着升高，而 CD4 和 CD4/CD8 显着降低。81.5 % (22/27) 的 IP 患者是病原体阴性，对糖皮质激素单药治疗反应良好。只有一名患者死亡，而其他患者从 IP 中恢复，随后接受了先前的化疗。19.2%（5/26）的IP患者出现IP复发，可能是由于糖皮质激素的初始剂量较低或停药速度较快的原因。多变量分析将男性、G-CSF、利妥昔单抗和聚乙二醇化脂质体阿霉素作为危险因素。IP 患者的 3 年 PFS 和 OS 分别为 74.1 % 和 46.9 %。

解释

我们建议应密切监测 IL-6、单核细胞和 CD4，尤其是在 R-CHOP/R-CDOP 组中。足够的初始剂量和基于放射学缓解的糖皮质激素缓慢减少是减少 IP 复发的关键策略。我们推测药物引起的免疫失衡可能会引发 IP，从而导致较低强度的细胞因子风暴，从而产生潜在的免疫治疗。这种并发症可能通过类似于 PD-1 的机制为患者的生存带来益处。