Incidence of Immune-Mediated Pseudoprogression of Lymphoma Treated with Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis

We evaluated the incidence of pseudoprogression and indeterminate response (IR) in patients with lymphoma treated with immune checkpoint inhibitors (ICIs). A systematic search of PubMed and EMBASE was performed up to 6 February 2021, using the keywords “lymphoma,” “immunotherapy,” and “pseudoprogression.” Random-effects models were used to calculate both pooled incidence of pseudoprogression patients with lymphoma and an IR according to LYRIC criteria, while the Higgins inconsistency index (I2) test and Cochran’s Q test were used for heterogeneity. Eight original articles were included, in which the number of patients ranged from 7 to 243. Among the lymphoma patients with ICIs, the pooled incidence of pseudoprogression was 10% (95% confidence interval [CI]: 0.06–0.17). There was no publication bias in Begg’s test (p = 0.14). Three articles were analyzed to determine the pooled incidence of pseudoprogression in patients with IR according to LYRIC criteria in a subgroup analysis, which was shown to be 19% (95% CI: 0.08–0.40). A significant proportion (10%) of patients with lymphoma treated with ICIs showed pseudoprogression, and 19% of patients with an IR response showed pseudoprogression and a delayed response. Immune-related response criteria such as LYRIC may be used for patients with lymphoma treated with ICIs.