Timing of steroid initiation and response rates to immune checkpoint inhibitors in metastatic cancer

Abstract

BackgroundCorticosteroids (CS) are the mainstay of immune-related adverse effect (irAE) management, as well as for other indications in cancer treatment. Previous studies evaluating whether CS affect immune checkpoint inhibitor (CPI) efficacy compared patients receiving CS versus no CS. However, there is a paucity of clinical data evaluating the timing of concomitant CS and CPI efficacy.MethodsWe retrospectively collected data from patients who received CS during CPI treatment at a single institution. Patients were in two cohorts based on timing of initiation of CS (≥2 months vs <2 months after initiating CPI). Patient characteristics, irAEs, cancer type, treatment type, treatment response/progression per RECIST V.1.1, and survival data were collected. Kaplan-Meier and Cox proportional hazard regression methods estimated HRs for the primary endpoint of progression-free survival (PFS) along with overall survival (OS).ResultsWe identified 247 patients with metastatic cancer who received CS concurrently with CPIs. The median time on CS was 1.8 months. After adjusting for treatment type, tumor type, brain metastases, and irAEs, those treated with CS ≥2 months after starting CPI had a statistically significant longer PFS (HR=0.30, p<0.001), and OS (HR 0.34, p<0.0001) than those who received CS <2 months after starting CPI. Objective response rate (ORR) for patients on CS ≥2 months was 39.8%, versus ORR for patients <2 months was 14.7% (p value =<0.001)ConclusionOur results suggest that early use of CS during CPI treatment significantly hinders CPI efficacy. This data needs to be validated prospectively. Future studies should focus on the immune mechanisms by which CSs affect T-cell function early in the CPI treatment course.

Monitoring and Management of the Patient with Immune Checkpoint Inhibitor-Induced Inflammatory Arthritis: Current Perspectives

“… 65 The negative association between corticosteroid treatment and survival is greatest when they are given within 2 months of ICI initiation. 66 This could, however, be because experiencing an early irAE necessitates early holding of the ICI, or because higher corticosteroid doses are needed for early irAE (eg, colitis) than for later ones (eg, endocrine). A long duration of corticosteroid use is associated with an increased infection risk 67 and with osteoporosis.…”

Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent but clinically inapparent in cancer patients under immune checkpoint therapy

“…Notably, one patient in our study experienced grade 2 CRS before any COVID-19 vaccination was administered, highlighting that CRS can occur independent of vaccination under ICT and may not necessarily be vaccine-related. This is particularly important in cancer patients in a palliative setting with limited treatment options, as CRS treatments such as glucocorticoids may impair ICT efficacy and deprive patients of an important treatment option (Iorgulescu et al, 2021;Maslov et al, 2021). Our results suggest that CRS-related cytokines are commonly induced after COVID-19 vaccination and not sufficient to establish the diagnosis of CRS.…”

Multimodality Advanced Cardiovascular and Molecular Imaging for Early Detection and Monitoring of Cancer Therapy-Associated Cardiotoxicity and the Role of Artificial Intelligence and Big Data

“…Emerging molecularly targeted probes against CD4, 89 Zr-DFO-CD4 and CD8 cells, 89 Zr-DFO-CD8a may be a potential avenue to detect inflammation at these earliest of stages, which can prompt more frequent follow ups, biomarker checking and earlier therapy (44). Determining specificity of these findings will also be important as to avoid withholding cancer fighting immunotherapy or treatment with steroids, which may potentially lower the efficacy of the immunotherapy agent (108)(109)(110). Checkpoint inhibitors have been shown to accelerate atherosclerosis and increase risk of plaque rupture in addition to the risk for myocarditis and pericarditis by driving increased inflammatory cells, including CD8 T cell infiltration into plaques in animal models and patients on checkpoint inhibitors (43,111,112).…”