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

Abstract

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.

Standardized classification schemes in reporting oncologic PET/CT

“…For those categorized as IR on initial therapy response 18 F-FDG PET, the same therapy is continued, and a new PET scan is obtained 12 weeks later (or earlier if clinically indicated), to reassess the response with respect to the nadir study, as shown in Table 3 ( 8 , 29 , 30 ). Although pseudoprogression has been documented in less than 10% of patients ( 31 , 32 ) in clinical practice these criteria are very useful since they provide flexibility in therapeutic decision-making; though to date, these criteria have not been widely validated. A recently published study ( 33 ) from the Lymphoma Study Association has suggested that LYRIC is useful only for early evaluation, with a 3.4% rate of pseudo-progression observed after 4 cycles of atezolizumab, venetoclax and obinutuzumab in relapsed or refractory DLBCL and FL but none after 8 cycles of therapy.…”

Evolution of Radiological Treatment Response Assessments for Cancer Immunotherapy: From iRECIST to Radiomics and Artificial Intelligence

“…A recent meta-analysis of solid tumors reported an overall pseudoprogression incidence of 6.0% in an ICI trial [ 6 ]. In another recent meta-analysis of patients with lymphoma, the incidence of pseudoprogression was reported as 10% [ 7 ]. Pseudoprogression can be assessed using new response criteria frameworks such as iRECIST, Immunotherapy Response Assessment in Neuro-Oncology (iRANO), or LYRIC.…”

“…Another challenge in making an accurate response assessment is the emergence of atypical response patterns, such as pseudoprogression or hyperprogression, following immunotherapy. Therefore, radiologists should also be familiar with the incidence, criteria, and imaging features associated with these atypical response patterns [ 5 6 7 ]. Current immune response assessment criteria, such as the Immune Response Evaluation Criteria in Solid Tumors (iRECIST) or LYmphoma Response to Immunomodulatory therapy Criteria (LYRIC), may also have limitations in terms of providing accurate response assessment following immunotherapy [ 5 ].…”

Immune Checkpoints: Therapeutic Targets for Pituitary Tumors

“…The use of immune checkpoint inhibitors has revolutionized the management of some tumors, but with different responses in different patients, and these drugs can cause unique adverse reactions that can be life threatening [ 67 – 69 ]. How to enhance the efficacy of immunosuppressive agents and reduce adverse reactions are two major challenges facing us.…”