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 |
|
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| 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 |
|
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| 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).