The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

The size of cancer-associated macrophage-like cells (CAMLs) and the level of programmed death-ligand 1 (PD-L1) expression in these cells may predict treatment outcomes in patients with non-small cell lung cancer (NSCLC), new research suggests.

The research was presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting by Daniel L. Adams, MD, of Creatv MicroTech, Inc. in Monmouth Junction, New Jersey.

Dr. Adams explained that CAMLs are phagocytic macrophages that can become engorged to greater than 50 µm in size, and this engorgement has been linked to rapid progression after chemoradiotherapy (CRT) in patients with NSCLC.

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“Further, we have shown that PD-L1 expression in CAMLs appear to dynamically change throughout chemoradiation induction, though the clinical meaning behind these changes remains unknown,” Dr Adams said.

Dr Adams and colleagues set out to determine whether engorged CAMLs remained a prognostic indicator in the immunotherapy setting and if changes in CAML PD-L1 correlated with progression-free survival (PFS).

The single-blind, prospective study included 168 patients with pathologically confirmed, unresectable NSCLC. There were 72 patients who received CRT alone and 96 who received CRT plus consolidation with PD-L1 immunotherapy, including atezolizumab (n = 39), durvalumab (n = 52), and pembrolizumab (n = 5).

To analyze CAML size and PD-L1 expression, blood samples of 15 mL were taken at baseline, at completion of CRT, and 1 month after CRT completion.

CAMLs were present in 90% of all samples tested, with an average of 5.8 CAMLs per 15 mL of blood, Dr Adams noted.

Having CAMLs of 50 µm or larger at baseline did not correlate with PFS in patients who received CRT alone (hazard ratio [HR], 1.3; 95% CI, 0.7-2.4; P =.593) or CRT plus immunotherapy (HR, 1.6; 95% CI, 0.8-2.9; P =.220).

However, having CAMLs of 50 µm or larger at completion of CRT was significantly associated with worse PFS in patients who received CRT alone (HR, 2.5; 95% CI, 2.5-5.1; P =.015) and in patients who received CRT with immunotherapy (HR, 2.7; 95% CI, 1.5-5.2; P =.003).

The researchers found that PD-L1 expression greater than 1% in primary tumor biopsies did not predict PFS after immunotherapy.

Similarly, having high CAML PD-L1 expression at baseline or at CRT completion did not predict PFS in patients who received CRT plus immunotherapy or those who received CRT alone.

However, the researchers observed a trend toward better PFS in patients who received CRT plus immunotherapy if they had high CAML PD-L1 expression at CRT completion (HR, 1.7; 95% CI, 0.9-3.3; P =.137).

In addition, significantly better PFS was seen in recipients of CRT and immunotherapy among patients who had high CAML PD-L1 expression at 1 month after CRT completion (HR, 3.2; 95% CI, 1.6-6.3;  P =.002).

“This appears to show that PD-L1 CAML expression correlates to better response via slower progression rates in patients with high PD-L1 CAMLs when treated with immunotherapy,” Dr Adams said.

Additional studies are needed to validate these findings, he added, and further subtyping and analyses are ongoing to evaluate overall survival and PD-L1 in CAMLs.

“In total, we confirm that large CAMLs of greater than 50 µm in size after CRT, regardless of IMT [immunotherapy] treatment, [were] 84% accurate in predicting progression, which validates a number of previous studies,” Dr Adams said in closing. “More interestingly, PD-L1 in phagocytic tumors in the blood appears to dramatically change in patients during different treatment, and these appear to predict for patients likely to respond to PD-L1 immunotherapy after completion of chemoradiation.”

Disclosures: This research was funded by the National Institutes of Health. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.


Adams, DL, Augustyn A, Heet J, et al. Sequential monitoring of PD-L1 on circulating stromal cells in blood predicts PFS in NSCLC patients undergoing immunotherapy after definitive chemoradiation. J Clin Oncol. 2021;39:(suppl 15; abstr 8534) doi:10.1200/JCO.2021.39.15_suppl.8534