Abstract PD9-02: Peripheral immune subsets and circulating tumor DNA (ctDNA) in patients (pts) with residual triple negative breast cancer (TNBC) treated with adjuvant immunotherapy and/or chemotherapy (chemo): The OXEL study
Authors: Lynce Filipa , Mainor Candace , Geng Xue , Jones Greg , Schlam Ilana , Wang Hongkun , Feger Ute , Donahue Renee , Toney Nicole , Jochems Caroline , Schlom Jeffrey , Gallagher Christopher , Nanda Rita , Graham Deena , Stringer-Reasor Erica M , Denduluri Neelima , Collins Julie , Dilawari Asma A , Chitalia Ami , Tiwari Shruti , Nunes Raquel , Kaltman Rebecca , Khoury Katia , Gatti-Mays Margaret , Swain Sandra M , Parsons Heather A. , Pohlmann Paula , Isaacs Claudine 
Published: March 2022

Background: Poor clinical outcomes are noted in pts with TNBC who do not achieve a pathologic complete response (pCR). We characterized peripheral immune subsets and the role of minimal residual disease (MRD) detection via ctDNA in pts who participated in the OXEL study. Methods: OXEL (Opdivo® -XELoda ®) is a recently completed phase II open-label 3-arm randomized study of nivolumab (nivo), capecitabine (cape) or the combination as adjuvant therapy (tx) for pts with residual TNBC after appropriate neoadjuvant chemo. Residual disease was defined as ≥ 1.0 cm of primary tumor and/or nodal involvement. Eligible pts had completed definitive local tx. Pts were randomly assigned to nivo 360 mg iv q3wks x 6 (arm A); cape 1250mg/m2 po bid D1-D14 q3 wks x 6 (arm B); nivo 360mg iv q3wks + cape 1250mg/m2 po bid D1-D14 q3 wks x 6 (arm C). Peripheral blood mononuclear cells (PBMCs) and ctDNA were assessed at baseline (D1 of cycle 1), 6, and 12 wks and at time of recurrence, if applicable. PBMCs were stained with 30 markers and analyzed by flow cytometry to identify changes in 158 immune cell subsets at 6 wks, as a percent of total PBMCs. RaDaRTM, a deep sequencing based, tumor-informed personalized assay was utilized to detect the presence of ctDNA in plasma. Distant disease-free survival (DDFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and Log-Rank test was used to compare DDFS and OS according to baseline MRD results. All pts will be followed for distant recurrence and survival for 3 yrs. Here we report the translational endpoints of the OXEL study. Clinical endpoints according to treatment received will be reported in a future analysis. Results: 45 pts were enrolled between 8/2018 and 6/2021. 29 (64%) were Caucasian and 14 (31%) were African American. Mean age at enrollment was 51 [+/- 12]. 93% of pts received a taxane-anthracycline containing neoadjuvant tx. 15 pts were randomized to each arm. DDFS probability at 1-yr and 2-yrs was 0.71 (+/- 0.07) and 0.66 (+/- 0.08) respectively. At 12 mos of median follow up, 13/45 pts (29%) experienced distant recurrence, none had local recurrence. 43 pts were evaluated for PBMC subsets. Changes in PBMC subsets at 6 wks were different amongst the arms; in arm A, reductions in NK subsets, including a 33% reduction in CD56dimCD16- cells, were observed, while in arm B, increases in naïve CD4+ T cells (+45%) and CD73+CD8+ T cells (+12%) and reductions in ki67+CD8+ T cells (-48%) were noted. In arm C, increases were observed in conventional dendritic cells (+36%), effector memory ki67+CD4+ T cells (+46%), and CD56dimCD16- NK cells (+29%). 33 pts underwent successful MRD analysis. 12/33 (36%) pts were MRD+ at baseline. 2/12 pts MRD+ at baseline subsequently cleared MRD, with undetectable ctDNA on future time points; neither patient has had recurrence to date. The remaining 10/12 MRD+ pts (83%) have experienced distance recurrence. 21/33 (64%) pts were ctDNA negative at baseline; 20/33 remained negative for all follow up timepoints. 10/11 pts experiencing distant recurrence were MRD+ at baseline, compared to 1/11 pt who became MRD+ at wk 6 post initiation of tx. At 12 mos of median follow-up, baseline MRD+ testing was significantly associated with an inferior DDFS ( p&lt;0.0001 Log-rank test, median DDFS 4.0 mos vs. not reached) and OS (p=0.02 Log-rank test, median OS not reached for both groups). Results will be updated at the time of abstract presentation. Conclusions: Changes in PBMC subsets were associated with receipt of chemo and/or immunotherapy. Our results suggest that baseline MRD+ in pts without pCR is a poor prognostic factor. Future trials aiming to optimize adjuvant treatment with chemo and/or immunotherapy in residual TNBC should consider incorporating ctDNA as a selection marker of pts at higher risk of recurrence.

Citation Format: Filipa Lynce, Candace Mainor, Xue Geng, Greg Jones, Ilana Schlam, Hongkun Wang, Ute Feger, Renee Donahue, Nicole Toney, Caroline Jochems, Jeffrey Schlom, Christopher Gallagher, Rita Nanda, Deena Graham, Erica M Stringer-Reasor, Neelima Denduluri, Julie Collins, Asma A Dilawari, Ami Chitalia, Shruti Tiwari, Raquel Nunes, Rebecca Kaltman, Katia Khoury, Margaret Gatti-Mays, Sandra M Swain, Heather A. Parsons, Paula Pohlmann, Claudine Isaacs. Peripheral immune subsets and circulating tumor DNA (ctDNA) in patients (pts) with residual triple negative breast cancer (TNBC) treated with adjuvant immunotherapy and/or chemotherapy (chemo): The OXEL study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD9-02.