Not all bad: Drug-induced interstitial pneumonia in DLBCL patients is potentially fatal but could be linked to better survival

Leuk Res. 2021 Dec:111:106688. doi: 10.1016/j.leukres.2021.106688. Epub 2021 Aug 18.

Abstract

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.

Keywords: Diffuse large B cell lymphoma; Drug induced lung toxicity; Granulocyte colony stimulating factor; Interstitial pneumonitis; Pegylated liposomal doxorubicin; Rituximab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Female
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Humans
  • Lung Diseases, Interstitial / chemically induced
  • Lung Diseases, Interstitial / immunology
  • Lung Diseases, Interstitial / mortality*
  • Lung Diseases, Interstitial / pathology
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / immunology
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage
  • Prednisone / administration & dosage
  • Prognosis
  • Retrospective Studies
  • Rituximab / administration & dosage
  • Survival Rate
  • Vincristine / administration & dosage

Substances

  • liposomal doxorubicin
  • Granulocyte Colony-Stimulating Factor
  • Polyethylene Glycols
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone