Patterns of pseudoprogression across different cancer entities treated with immune checkpoint inhibitors.

BACKGROUND: Pseudoprogression (PsPD) is a rare response pattern to immune checkpoint inhibitor (ICI) therapy in oncology. This study aims to reveal imaging features of PsPD, and their association to other relevant findings. METHODS: Patients with PsPD who had at least three consecutive cross-sectional imaging studies at our comprehensive cancer center were retrospectively analyzed. Treatment response was assessed according to immune Response Evaluation Criteria in Solid Tumors (iRECIST). PsPD was defined as the occurrence of immune unconfirmed progressive disease (iUPD) without follow-up confirmation. Target lesions (TL), non-target lesions (NTL), new lesions (NL) were analyzed over time. Tumor markers and immune-related adverse events (irAE) were correlated. RESULTS: Thirty-two patients were included (mean age: 66.7 ± 13.6 years, 21.9% female) with mean baseline STL of 69.7 mm ± 55.6 mm. PsPD was observed in twenty-six patients (81.3%) at FU1, and no cases occurred after FU4. Patients with iUPD exhibited the following: TL increase in twelve patients, (37.5%), NTL increase in seven patients (21.9%), NL appearance in six patients (18.8%), and combinations thereof in four patients (12.5%). The mean and maximum increase for first iUPD in sum of TL was 19.8 and 96.8 mm (+ 700.8%). The mean and maximum decrease in sum of TL between iUPD and consecutive follow-up was - 19.1 mm and - 114.8 mm (-60.9%) respectively. The mean and maximum sum of new TL at first iUPD timepoint were 7.6 and 82.0 mm respectively. In two patients (10.5%), tumor-specific serologic markers were elevated at first iUPD, while the rest were stable or decreased among the other PsPD cases (89.5%). In fourteen patients (43.8%), irAE were observed. CONCLUSIONS: PsPD occurred most frequently at FU1 after initiation of ICI treatment. The two most prevalent reasons for PsPD were TL und NTL progression, with an increase in TL diameter commonly below + 100%. In few cases, PsPD was observed even if tumor markers were rising compared to baseline. Our findings also suggest a correlation between PsPD and irAE. These findings may guide decision-making of ICI continuation in suspected PsPD.

Influence of Adipose Tissue Distribution, Sarcopenia, and Nutritional Status on Clinical Outcomes After CD19 CAR T-cell Therapy.

Although CD19-directed chimeric antigen receptor T-cell therapy (CD19.CAR-T) has proven clinical efficacy for multiple refractory B-cell malignancies, over 50% of patients ultimately relapse. Recent evidence has underlined the critical role of the host in determining treatment responses. In this retrospective observational study of 106 patients with relapsed/refractory large B-cell lymphoma receiving standard-of-care CD19.CAR-T, we analyzed the impact of immunometabolic host features and detailed body composition measurements on post-CAR T clinical outcomes. We extracted muscle and adipose tissue distributions from prelymphodepletion CT images and assessed laboratory-based immuno-nutritional scores. Early responders displayed increased total abdominal adipose tissue deposits (TAT: 336 mm3 vs. 266 mm3, P = 0.008) and favorable immuno-nutritional scores compared to nonresponding patients. On univariate Cox regression analysis, visceral fat distribution, sarcopenia, and nutritional indices significantly impacted both progression-free (PFS) and overall survival (OS). Patients with a low skeletal muscle index (SMI; e.g.<34.5), a sarcopenia indicator, exhibited poor clinical outcomes (mOS 3.0 months vs. 17.6 months, log-rank P = 0.0026). Prognostically adverse immuno-nutritional scores were linked to inferior survival [low PNI: HROS, 6.31; 95% confidence interval (CI), 3.35-11.90; P < 0.001]. In a multivariable analysis adjusting for baseline Eastern Cooperative Oncology Group performance status, C-reactive protein, and lactate dehydrogenase, increased TAT was independently associated with improved clinical outcomes (adjusted HROS, 0.27; 95% CI, 0.08-0.90; P = 0.03). We noted particularly favorable treatment outcomes in patients with both increased abdominal fat and muscle mass (TAThigh/SMIhigh: 1-year PFS 50%, 1-year OS 83%). These real-world data provide evidence for a role of body composition and immuno-nutritional status in the context of CD19.CAR-T and suggest that the obesity paradox may extend to modern T cell-based immunotherapies. See related Spotlight by Nawas and Scordo, p. 704.