Table 2.

Outcomes of patients who developed disease progression during or after reduced-frequency dosing

	Disease type	Time on anti-PD-1 therapy	BOR 1st course	Status of anti-PD-1 therapy at progression	Site(s) of progression	New site of metastatic disease?	Therapy for PD	BOR 2nd course	Time on therapy	Disease status at follow up
1	Cutaneous melanoma	47 months (SFD 26; RFD 21)	SD	OFF therapy for 14 months electively	Lymph nodes	No	nivolumab (SFD 16 months; RFD 19 months)	PR	35 months	Ongoing partial response
2	Cutaneous melanoma	23 months (SFD 16; RFD 7)	SD	Receiving nivolumab 240 mg every 2 months	Leptomeninges	No	BRAF/MEK inhibitor therapy	PD	1.9 months	Died
3	Cutaneous melanoma	16 months (SFD 13; RFD 3)	SD	OFF therapy for 11 months due irAE (Hepatitis)	Brain	Yes	SRS; no systemic therapy	N/A	N/A	No evidence of disease progression for 36 months
4	Merkel cell carcinoma	50 months (SFD 14; RFD 36)	PR	OFF therapy for 22 months due to irAE (Colitis)	Lymph nodes, retroperitoneum	No	RT to perinephric mass, pembrolizumab (Standard frequency)	PD	2 months	Died

SFD Standard frequency dosing, RFD Reduced frequency dosing, BOR Best overall response, PR Partial response, SD Stable disease, PD Progressive disease, SRS Stereotactic radiosurgery, RT Radiation therapy

Among the four patients with disease progression, three of the patients had previously discontinued systemic therapy at the time of progression. The time interval between cessation of immunotherapy and progression of disease ranged from 11 to 22 months. Two patients restarted immunotherapy, and one of the two patients experienced a partial response to anti-PD-1 therapy after reinitiating therapy