Near complete remission of pulmonary metastases in triple negative breast cancer (TNBC) using low-dose immune checkpoint (IC) inhibitors with high dose (HD) interleukin-2 (IL-2) and fever range hyperthermia.

Abstract

e23111 Background: TNBC is more aggressive, has shorter disease-free and overall survival times than other breast cancer subtypes. Due to the lack of personalized therapies interest is increasing for novel strategies in the metastatic setting. Scientific basis:prolonged low dose anti-CTLA-4 and anti-PD-1 IC blockade with HD IL-2 treatment would be safe and effective in patients with high tumor burden. Methods: Diagnosis of a 50-yr old female patient was primary TNBC with lymphadenopathy and disseminated lung metastases. First, an off-label low-dose PD-1 IC inhibitor nivolumab (0.5 mg/kg) with CTLA-4 IC inhibitor ipilimumab (0.3 mg/kg) was administered weekly, over three weeks. This was accompanied by loco-regional hyperthermia with radiofrequency fields (13.56 MHz) 3 times per week (max. output 400 W) over the thoracic region in combination with Vitamin-C (0.5 g/kg) and alpha lipoic acid (600 mg) over three weeks. This was followed by long duration fever range whole body hyperthermia in combination with low dose cyclophosphamide (300 mg/m²) to down modulate Treg cells. Then, a HD IL-2 (54 Mio/m2 as decrescendo regimen) therapy was administered under Taurolidine protection for five days. Results: The patient presented with widespread disease with a Karnofsky score (Ks) of 80%, felt severe pain in the left lateral chest wall during inspiration that became extremely painful during sneezing. She complained about severe shortness of breath (SOB) on exertion, lack of appetite, insomnia, and exhaustion. Six months later, chest X-ray demonstrated near complete remission of pulmonary metastases. SOB on exertion or any other cancer related symptoms vanished, Ks returned to 100%. Conclusions: We assumed that a frequently administered low dose IC blockade would prevent T cell exhaustion and premature apoptosis making main stream HD IL-2 stimulation treatment safer and more effective. Following the success of this woman, we treated seven more patients with disseminated metastases of different origins, who are responding similarly to the presented TNBC case. This combination treatment warrants further studies.