Table 8.
Comparison of patients’ characteristics and overall results for nivolumab, pembrolizumab, sintilimab, and tislelizumab phase II trials for rr-cHL.
| Patients’ Characteristics and Key Outcome and Toxicity Measures | Nivolumab [124,127,128] | Pembrolizumab [125,126] | Sintilimab [133] | Tislelizumab [134] |
|---|---|---|---|---|
| Trial Name/Code | Checkmate 205 | KEYNOTE-087 | ORIENT-1 | BGB-A317-203 |
| Location | Europe, North America | Europe, North America, Israel, Australia, Japan | China | China |
| Dose/Schedule | 3 mg/kg every 2 weeks | 200 mg every 3 weeks | 200 mg every 3 weeks | 200 mg every 3 weeks |
| Duration of treatment | Until PD or unacceptable toxicity § | Until PD or unacceptable toxicity or investigator decision or max of 24 months ¶ | Until PD or unacceptable toxicity or max of 24 months | Until PD or unacceptable toxicity |
| Treatment beyond progression | Accepted per early protocol amendment (see text) | Permitted for clinically stable patients if agreed on by investigator and sponsor | Accepted for clinically stable patients if agreed on by investigator and sponsor | NR |
| Inclusion criteria | 3 different clinical scenarios (arms A, B, C) always after autoSCT and after BV in Arms B and, partly, C (see Table 9) | 3 different clinical scenarios (cohorts 1, 2, 3) after autoSCT (cohorts 1, 3) and after BV (cohorts 1, 2, and partly 3) (see Table 9) | rr-cHL after ≥2 lines of Tx (previous autoSCT and BV not required) in 18 Chinese hospitals | rr-cHL after autoSCT failure or ≥2 lines of Tx if autoSCT ineligible in 11 Chinese hospitals |
| Primary endpoint | ORR by IRC [55] | ORR by IRC [55] and safety | ORR by IRC (PET or CT) | ORR by IRC [129] |
| Patients (#) | 243 | 210 | 92 | 70 |
| Age (median (Range)) | 34 (26–46) † | 35 (18–76) | 33 (28–43) | 32.5 (NR) |
| Age ≥ 65 years (%) | 6 §§ | 8.6 | 0 | 6 |
| ECOG PS 0–1 (%) | 100 | 100 | 99 | NR |
| Previous lines of Tx (median (range)) | 4 (3–5) † | 4 (1–12) | 3 (2–5) | 3 (2–11) |
| ≥3 lines of previous Tx (%) | 85 | 87 | 68 | NR |
| Ineligible for autoSCT (%) | 0 | 39 | NR | 81 * |
| Previous ASCT (%) | 100 | 61 | 19 | 19 |
| Previous BV (%) | 74 | 83 | 6 | 21 ** |
| Median follow-up (months) | 33.0 | 27.6 | 10.5 | 7.9 |
| ORR per IRC (%) | 71 | 72 | 80 | 86 |
| CR rate per IRC (%) | 21 | 28 | 34 | 61 |
| Progression free survival (PFS) | 15 mo (median) | 13.7 mo (median) | 77.6% at 6 months | 80% at 6 months |
| Duration of response | 18 mo (median) †† | 16.5 mo (median) †† | ~79% at 6 months | NR |
| Overall survival | ~87–88% at 2 yrs | 90.9% at 2 yrs | No deaths | 1 death of PD |
| Discontinuation (patient number (%)) | 26 (11%) ¶ | 14 (6.7%) ¶ | 3 (3%) ¶ | 4 (5.7%) |
| Toxicity | ||||
| TRAEs in ≥ 10% of patients | Rash, fatigue, diarrhea, pruritus, nausea, IRRs | Rash, fatigue, hypothyroidism, pyrexia | Pyrexia, rash, hypothyroidism, pneumonitis, increased ALT, leukopenia | Pyrexia, hypothyroidism, increased weight, upper respiratory tract infection, cough |
| TRAEs gr. 3/4 in ≥ 2% of patients | lipase elevations, neutropenia, ALT elevations | neutropenia | pyrexia, IRRs, lung infection | pneumonitis, upper respiratory tract infection |
| TRAEs of special interest | hypothyroidism/thyroiditis (12%), pneumonitis (4%), hyperthyroidism (2%) but none gr. 3/4, rash 9%, hepatitis 5% (4% gr. 3/4) | hypothyroidism (16%), pneumonitis (5%), hyperthyroidism (4%) but none gr. 3/4 | hypothyroidism (20%), pneumonitis (10%; only 1% gr.3/4) | hypothyroidism (30%), pneumonitis |
IRC = independent review committee; IRRs = infusion-related reactions; NR = not reported; TRAEs = treatment-related adverse events. NOTE: Comparisons are not meaningful between nivo/pembro and sintilimab/tislelizumab because of highly different eligibility criteria and follow-up times. Even toxicities are difficult to compare due to the very different follow-up times. * 76% due to chemorefractoriness; ** immunotherapy in general, including BV; § In arm C only, patients were to discontinue nivolumab after one year in persistent CR and treatment could be resumed if relapse occurred within two years from the last dose; ¶ Patients attaining CR could stop treatment after a minimum of six months and ≥2 doses after CR; † numbers in parentheses are interquartile range (IQR); §§ ≥60 years; ††median duration of response for CRs versus PRs: for nivolumab 32 versus 13 months and for pembrolizumab not reached versus 10.9 months; ¶ most frequent causes; Nivolumab: IMRAEs including pneumonitis (2%) and autoimmune hepatitis (1%); Pembrolizumab: pneumonitis (3%), IRRs (1%), single cases of various IMRAEs; Sintilimab: pneumonitis (n = 2 plus thrombocytopenia in 1), liver function abnormalities (n = 1); Tislelizumab: pneumonitis (n = 2), organizing pneumonia (n = 1), focal segmental glomerulosclerosis (n = 1).