Ying Zhou, Chenchen Zhu, Zhen Shen, Yanhu Xie, Wei Zhang, Jing Zhu, Tianjiao Zhang, Min Li, Jiwei Qin, Shuai Yin, Rongzhu Chen, Wei Wei, Sinan Sun, Guihong Wang, Zheng Zhou, Hanhui Yao, Dabao Wu and Björn Nashan
Wei Nie, Jie Qian, Mi-Die Xu, Kai Gu, Fang-Fei Qian, Jun Lu, Xue-Yan Zhang, Hui-Min Wang, Bo Yan, Bo Zhang, Shu-Yuan Wang, Fang Hu, Chang-Hui Li, Hua Zhong and Bao-Hui Han
Background: Biomarkers for chemotherapy efficacy in non–small cell lung cancer (NSCLC) are lacking. This retrospective study assesses the association between blood-based tumor mutational burden (bTMB) and clinical benefit of chemotherapy. Methods: Clinical and targeted next-generation sequencing data from the OAK trial (training set; n=318) and POPLAR trial (validation set; n=106) in the docetaxel arm were analyzed. The cutoff value of bTMB for outcome prediction was determined based on a time-dependent receiver operating characteristic curve in the training set, and propensity score matching (PSM) was conducted. The primary outcome was overall survival (OS). Durable clinical benefit (DCB) was defined as OS lasting >12 months. Interaction between treatment and bTMB was assessed in the combined set. Results: A lower bTMB was observed in patients with DCB compared with no durable benefit, and in those with a partial response and stable disease compared with progressive disease. The optimized cutoff value of bTMB for predicting OS was 7 single-nucleotide variants per megabase. In the training set, a low bTMB was significantly associated with longer OS and progression-free survival (PFS). The prognostic value of bTMB was confirmed in the validation set and PSM set. The interaction between bTMB and treatment was significant for PFS (interaction P=.043) in the combined set. Mutations in KEAP1 were associated with high bTMB and a lack of benefit from chemotherapy. Conclusions: Low bTMB is associated with a survival advantage in patients with NSCLC treated with docetaxel, suggesting the prognostic and predictive potential of bTMB for determining chemotherapy efficacy.
Fangwen Zou, Hamzah Abu-Sbeih, Weijie Ma, Yuanzun Peng, Wei Qiao, Jianbo Wang, Amishi Y. Shah, Isabella C. Glitza Oliva, Sarina A. Piha-Paul, John A. Thompson, Hao Chi Zhang, Anusha S. Thomas and Yinghong Wang
Background: Immune-mediated diarrhea and colitis (IMDC) is a common immune-related adverse effect related to immune checkpoint inhibitors. We aimed to identify risk factors for chronic IMDC and its prognostic value in cancer outcomes. Methods: We retrospectively collected data on patients with a diagnosis of IMDC between January 2018 and October 2019 and grouped them based on disease duration into acute (≤3 months) and chronic (>3 months) categories. A logistic regression model and the Kaplan-Meier method with log-rank tests were used for biostatistical analysis. Results: In our sample of 88 patients, 43 were in the chronic group and 45 were in the acute group. Genitourinary cancer and melanoma accounted for 70% of malignancies. PD-1/L1 monotherapy (52%) was the more frequently used regimen. We showed that chronic IMDC was associated with proton pump inhibitor use (odds ratio [OR], 3.96; P=.026), long duration of IMDC symptoms (OR, 1.05; P<.001) and hospitalization (OR, 1.07; P=.043), a histologic feature of chronic active colitis (OR, 4.8; P=.025) or microscopic colitis (OR, 5.0; P=.045), and delayed introduction of selective immunosuppressive therapy (infliximab/vedolizumab; OR, 1.06; P=.047). Chronic IMDC also reflected a better cancer response to immune checkpoint inhibitors (30% vs 51%; P=.002) and was accompanied by improved overall survival (P=.035). Similarly, higher doses of selective immunosuppressive therapy were associated with better overall survival (P=.018). Conclusions: Chronic IMDC can develop among patients with a more aggressive disease course and chronic features on colon histology. It likely reflects a prolonged immune checkpoint inhibitor effect and is associated with better cancer outcome and overall survival.
Sanjeev Kumar Gupta, Nitin Jain, Guilin Tang, Andrew Futreal, Sa A. Wang, Joseph D. Khoury, Richard K. Yang, Hong Fang, Keyur P. Patel, Rajyalakshmi Luthra, Mark Routbort, Bedia A. Barkoh, Wei Chen, Xizeng Mao, Jianhua Zhang, L. Jeffrey Medeiros, Carlos E. Bueso-Ramos and Sanam Loghavi
RNA-seq was used to identify the partner gene and confirm the presence of a BCR-PDGFRB fusion. Identification of this fusion product resulted in successful treatment and long-term remission of this myeloid neoplasm. Based on our results, we suggest that despite current WHO recommendations, screening for PDGFRB rearrangement in cases of leukocytosis with eosinophilia and no other etiologic explanation is necessary, even if the karyotype is normal.