Predictors of survival outcomes in patients (pts) with advanced solid tumors treated with cellular therapies in early clinical trials.
Authors: Nardo Mirella , Gouda Mohamed Alaa , Ahmed Jibran , NOIA BARRETO CARMELIA MARIA , Nelson Blessie Elizabeth , Araujo Dejka M. , Blumenschein George R. , Tsimberidou Apostolia Maria , Piha-Paul Sarina A. , Dumbrava Ecaterina Elena , Hong David S. 
Published: June 2023

e14532

Background: Treatment strategies utilizing adoptive cell therapies (ACT) have shown promising survival benefits for hematologic malignancies. ACT are also known for the potential high-risk side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Numerous ACT have been tested for solid tumors in phase 1 clinical trials, however no prognostic biomarkers were reported previously. We investigated prognostic markers for toxicities and survival outcomes of pts with solid tumors treated with ACT in a Phase 1 Program. Methods: Pts with advanced or metastatic solid tumors were enrolled in phase 1 ACT trials in the Investigational Cancer Therapeutics Department at The University of Texas MD Anderson Cancer Center. MD Anderson Cancer Center (MDACC) prognosis score was calculated based on the number sites of metastatic sites, lactate dehydrogenase (LDH), albumin, performance status (ECOG) and if gastrointestinal (GI) primary tumors. Clinical and biological characteristics were collected from prospectively maintained electronic medical records and databases. Results: From August 29, 2017 to May 19, 2022, 72 pts received cell therapy in 11 clinical trials. A total of 58% were female (n = 42), 89% white (n = 64) and 26% had GI cancers (n = 19). The median number of prior treatment lines was 3 (interquartile range - IQR = 2) and all pts had received prior chemotherapy. The median baseline MDACC score for all participants was 2 (IQR = 1). The median overall survival (OS) was 7 months (95% CI 5.1-8.8). Day 30+, Day 100+, and Day 365+ mortality rates were 3% (n = 2), 19% (n = 14), and 64% (n = 46), respectively. In total, 64% (n = 46) of pts experienced CRS, with 3 pts having > grade 2, while 13% (n = 9) experienced ICANS, with 1 pt having > grade 2 toxicity. Factors associated with higher rates of mortality at Day 100+ included a diagnosis of GI cancer (37% vs 13%, p = 0.041), more than 2 metastatic sites (37% vs 8.9%, p = 0.003), lung metastasis (29% vs 10.5%, p = 0.043), cardiovascular comorbidity (42% vs 15%, p = 0.048), and MDACC score greater than 1 (33% vs 3%, p = 0.001). Median overall survival (OS) was significantly shorter in pts with GI cancer diagnosis when compared to other cancer types (5 vs 8 months, p = 0.007), no history of prior targeted therapy (7 vs 8 months, p = 0.028), albumin < 3.5 (0 vs 6 months, p < 0.001), hemoglobin < 12 (6 vs 10 months, p = 0.006), and MDACC score > 1 (5 vs 12 months, p = 0.017). Conclusions: MDACC prognosis score of greater than 1 was associated with a reduced OS of pts with advanced solid tumors who received ACT in a phase I clinical trial setting. Further investigation is warranted in larger populations to validate these prognostic factors.