Immune Checkpoint Inhibition in Classical Hodgkin Lymphoma: From Early Achievements towards New Perspectives

Table 2

Clinical trials of immune checkpoint inhibitors in cHL.

Study	Year	Drug, dose	Design	Phase	Clinical setting	No. of patients	ORR, %	CR, %	PFS
Ansell et al. (Checkmate 039) [7]	2015	Nivolumab, 3 mg/kg iv every 2 weeks until complete response, tumor; progression, or excessive toxic effects	P	I	R/R	23	87	17	86% at 24 weeks
Armand et al. Checkmate 205 updated results (ASH 2018) [58]	2018	Nivolumab, 3 mg/kg iv every 2 weeks until disease progression,; death, unacceptable toxicity, withdrawal of consent, or; study end.∗; Patients in cohort C discontinue nivolumab after 1 year in persistent CR and could resume treatment if they relapsed within 2 years of the last dose	P; Composed of 3 cohorts	II	R/R	243	69	16	Median PFS 15 months
			Cohort A; (no exposition to BV)			63	65	29	Median PFS 17 months
			Cohort B (treatment with BV after auto-HSCT)			80	68	13	Median PFS 12 months
			Cohort C (treatment with BV before and/or after auto-HSCT failure)			100	73	12	Median PFS 15 months
Maruyama et al. [60]	2017	Nivolumab, 3 mg/kg iv on Day 1 each 14-day cycle.	P	II	R/R	17	81.3	23.5	60% at 6 months
Armand et al. (Keynote 013) [61]	2016	Pembrolizumab iv; at a dose of 10 mg/kg every 2 weeks	P	I	R/R	31	65	16	69% at 24 weeks, 46% at 52 weeks
Zinzani et al. Keynote 087 updated results (ASH 2018) [63]	2018	Pembrolizumab, 200 mg iv every 3 weeks; without premedication for a maximum of 24 months or until documented; confirmed disease progression, intolerable toxicity, or investigator; decision	P; Composed of 3 cohorts	II	R/R	210	71.9	27.6	Median PFS 13.7 months
			Cohort 1 (progression after auto-HSCT and BV)			69	76.8	26.1	Median PFS 16.4 months
			Cohort 2 (progression after salvage chemotherapy and BV, but ineligible for auto-HSCT because of chemoresistant disease)			81	66.7	25.9	Median PFS 11.1 months
			Cohort 3 (progression after auto-HSCT, without BV)			60	73.3	31.7	Median PFS 19.4 months
Shi et al. (ORIENT-1) [68]	2019	Sintilimab, 200mg iv once every 3 weeks, until disease progression, death, unacceptable toxicity or withdrawal of consent, for a maximum of 24 months	P	II	R/R	92	80,4	34	77.6% at 6 months
Herbaux et al. [71]	2017	Nivolumab, 3 mg/kg iv once every; 2 weeks without premedication until disease progression or unacceptable; toxicity as assessed by investigators	R	-	R/R after allo-HSCT	20	95	42	58.2% at 12 months
Haverkos et al. [72]	2017	Nivolumab 3mg/kg iv every 2 weeks (n=28) or Pembrolizumab 200mg iv every 3 weeks (n=2)	R	-	R/R after allo-HSCT	30	79	50	Median PFS 591 days

BV = brentuximab vedotin, CR= complete response, HSCT= hematopoietic stem cell transplantation, IV = intravenously, NA = Not Available, ORR= overall response rate, P= prospective, PFS= progression free survival, R= retrospective, R/R= relapsed or refractory disease.
∗Amendment in July 2014: patients continued treatment beyond progression if protocol-predefined criteria were met (i.e. stable performance status and deriving perceived clinical benefit). Patients treated beyond initial progression were required to discontinue in the event of further progression (>10% further increase in tumor burden).