Long-Term Remission with Ipilimumab/Nivolumab in Two Patients with Different Soft Tissue Sarcoma Subtypes and No PD-L1 Expression

Abstract

Checkpoint inhibitor therapy has been shown to improve outcomes in multiple solid malignancies; however, data are limited in soft tissue sarcoma. We present two cases of patients with advanced soft tissue sarcoma of different subtypes (dedifferentiated liposarcoma and myxofibrosarcoma) with zero percent PD-L1 expression by immunohistochemistry who were treated with ipilimumab and nivolumab followed by maintenance nivolumab. Both patients had failed multiple lines of systemic treatment and experienced long-term remission after starting ipilimumab and nivolumab. Genetic testing revealed that no genetic mutations were found in common between the two cases. One patient received concurrent cryoablation, which may have sensitized his tumor to immunotherapy. Checkpoint inhibitor therapy may improve outcomes in soft tissue sarcoma regardless of PD-L1 status, especially when combined with cryoablation. Studies are needed to evaluate whether treatment response varies by sarcoma subtype and what molecular markers can be used to guide patient selection.

Keywords: Ipilimumab; Nivolumab; PD-1 blockade; PD-L1 status; Sarcoma.

Fig. 1

Response of axillary dedifferentiated liposarcoma to treatment with ipilimumab and nivolumab: 1 week before starting treatment (A), cycle 2 day 11 (B), cycle 2 day 21 (C), cycle 4 day 1 (D), and cycle 7 day 1 (E). The patient received four cycles of induction therapy about 21 days each; cycle 3 was delayed by 2 days, and cycle 4 was delayed by 1 day. After completing induction therapy, the patient received maintenance therapy about every 14 days for cycles 5 and 6, and about every 28 days starting cycle 7. The patient received concurrent cryoablation on cycle 3 day 20.

Fig. 2

Baseline and follow-up radiographic imaging of the patient with dedifferentiated liposarcoma treated with ipilimumab and nivolumab followed by maintenance nivolumab therapy, with concurrent cryoablation. Top: cycle 1 day 1, axillary mass measuring 8.1 × 5.9 × 9.8 cm with SUV max 12.2; middle: cycle 5 day 8, largely resolved mass with SUV max 4.7; bottom: cycle 10 day 1, stable or improving posttreatment changes. A yellow arrow indicates the lesions.

Fig. 3

Baseline and follow-up radiographic imaging of the patient with myxofibrosarcoma treated with ipilimumab and nivolumab followed by maintenance nivolumab therapy. Top: 1 week before starting treatment; middle: cycle 19 day 14; bottom: 21 months after starting treatment.