Immuno-Oncology Resource Center
Immuno-Oncology Resource Center
November 25, 2019
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Adjuvant Cytokine-Induced Killer Cell Therapy Improves Survival in Postoperative Breast Cancer

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An analysis of patients with postoperative breast cancer has shown increased OS and RFS among patients who received adjuvant therapy with cytokine-induced killer cell infusion, according to the results of a retrospective study published in Journal of ImmunoTherapy of Cancer.

Additionally, the study showed that PD-L1 expression was an independent prognostic factor that predicted survival benefit from CIK treatment.

“A series of studies has shown that CIK-based treatment could significantly improve the prognosis of both hematologic malignancies and solid tumors, including breast cancer,” Zi-Qi Zhou, with Sun Yat-Sen University Cancer Center, and colleagues wrote. “However, not all tumor patients who receive CIK cell infusion exhibit improved outcomes; some patients are nonresponsive. Therefore, we sought to investigate what methods can identify patients who are suitable for CIK cell treatment.”

The investigators conducted a retrospective analysis of medical records of women who had CIK cell immunotherapy after undergoing surgery for breast cancer at Sun Yat-Sen University Cancer Center in Guangzhou, China, between December 1, 2009, and December 31, 2013. Surgeries included quadrantectomy or mastectomy and axillary lymph node dissection. The records review yielded 301 qualified patients, with 150 patients who received adjuvant CIK immunotherapy (CIK group) and 160 patients who did not (control group). Most patients were older than 50 years in both groups and had stage 3 TNM tumors. Most patients also expressed PD-L1 in both groups (n = 118 in the CIK group; n = 106 in the control group).

Follow-up visits were conducted every 3 months for the first 2 years after surgery, followed by every 6 months for 2 years and then once annually.

Patients who received adjuvant CIK immunotherapy had their blood collected about 2 weeks after surgery, once their blood levels had returned to normal. The cells were then cultured with CIK cells harvested on day 14 of the process. Patients were then infused with four cycles of autologous CIK cells with a 2-week interval between every 2 cycles.

Patient tissue samples also underwent subsequent immunohistochemical analysis to determine PD-L1 expression.

The investigators’ analysis showed that 5-year OS was significantly better in the CIK group compared with the control group (85.7% vs. 72.3%; HR = 0.502; 95% CI, 0.309-0.819). Five-year RFS rates were also significantly better in the CIK group compared with the control group (80.8% vs. 68.6%; HR = 0.563; 95% CI, 0.359-0.884).

Multivariate analysis of the results showed that TNM stage and PD-L1 expression were independent prognostic factors for patients who received adjuvant CIK immunotherapy.

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The 5-year OS rate of patients in the PD-L1-postivie group was 95.2%, and the 5-year RFS rate was 87.6%. Five-year OS and RFS rates in the PD-L1-negative group were 77.1 and 76.4%, respectively.

“The Cox proportional regression analyses showed that PD-L1 expression was an independent prognostic factor for postoperative CIK treatment,” Zhou and colleagues wrote.

“In addition, when 5% was used as a stratification standard to distinguish all the patients, people who received CIK cell infusion had prolonged OS and RFS in the PD-L1 5% expression cohort. Therefore, we think that over 5% PD-L1 tumor expression can be used as a predictor of CIK-assisted immunotherapy for postoperative breast cancer patients after comprehensive treatment.”

Twelve patients experienced adverse events related to CIK cell treatment. Treatment-related adverse events included fever (4 patients), fatigue and anorexia (3 patients), nausea/vomiting (1 patient) and transient hypertension (1 patient). The median time to onset of therapy-related adverse events was 4.5 hours (range, 0.5–30 hours), with a median duration of 12 hours (range, 0.5–36.0 hours).

“We confirmed that CIK immunotherapy could improve the prognosis of breast cancer patients and for the first time revealed that PD-L1 expression in the tumor is as an indicator of adjuvant CIK therapy for postoperative breast cancer,” the investigators wrote. “Our findings on the relationship between PD-L1 expression and CIK therapy [c]ould provide new insights into the theory of tumor immunotherapy. Additional multicenter and large-sample validation studies are required to verify our results.” – by Drew Amorosi

Disclosures: The authors report no relevant financial disclosures.