Table 2 Available results of clinical trials for PD-1/PD-L1 inhibitor in treatment of MDS/AML
From: Targeting PD-1/PD-L1 pathway in myelodysplastic syndromes and acute myeloid leukemia
Reference | Trial phase | Patient characteristics | Intervention | Target | Efficacy | Toxicity |
|---|---|---|---|---|---|---|
Berger et al. [122] | I, single-arm | 8 R/R AML (4 AML relapsed after allo-SCT) and 1 MDS | CT-011 (0.2–6 mg/kg) | PD-1 | One AML patient achieved peripheral blasts reduction | 50% AML patients experienced grade 3–4 AEs and died (due to fulminate resistant leukemia but not study drug) |
Garcia-Manero et al. [127] | Ib, single-arm | 28 HMA-failure MDS | Pembrolizumab 10Â mg/kg, Q2weeks | PD-1 | ORR 4%; CR 0% OS rate 49% at 24Â weeks | Hypothyroidism (14%), fatigue (11%), 7% grade 3/4 treatment-related AEs: 1 gastroenteritis (grade 3) and 1 TLS (grade 4) |
Garcia-Manero et al. [128] | II, multi-arms non-randomized | 15 HMA-failure MDS | Nivolumab 3Â mg/kg on day 1 and 15 Q4weeks | PD-1 | ORR 35%; CR/CRp 15%; mOS NR | Skin rash (11%); fatigue (9%); pain (7%); infection (6%); FN (5%); pruritus (6%); diarrhea (5%); constipation (4%); nausea (4%); ALT elevations (3%); anorexia (3%); and cough (3%) One early mortality |
20 HMA-failure MDS | Ipilimumab 3Â mg/kg Q3weeks | CTLA-4 | ORR 13%; CR/CRp 0%; mOS 8 mos | |||
20 treatment-naïve MDS | Nivolumab 3 mg/kg on day 6 and 20, plus AZA 75 mg/m2 daily for 7 days Q4weeks | PD-1 + HMA | ORR 75%; CR/CRp 50%; mOS 12 mos | |||
21 treatment-naïve MDS | Ipilimumab 3 mg/kg on day 6, plus AZA 75 mg/m2 daily for 7 days Q4weeks | CTLA-4 + HMA | ORR 71%; CR/CRp 38%; mOS 8 mos | |||
Chien et al. [132] | II, single arm | 17 treatment-naïve MDS | Pembrolizumab 200 mg Q3weeks, plus AZA 75 mg/m2 daily for 7 days Q4weeks | PD-1 + HMA | ORR 76%; CR 3%; mOS NR | Arthralgias (40%), pneumonia (33%), nausea (27%). One patient died within first 60 days due to unrelated cause of ventricular fibrillation |
20 HMA-failure MDS | Pembrolizumab 200 mg Q3weeks, plus AZA 75 mg/m2 daily for 7 days Q4weeks | PD-1 + HMA | ORR 25%; CR 5%; mOS 5.8 mos | Pneumonia (32%), arthralgias (24%), constipation (24%). Two patients died within first 60 days | ||
Daver et al. [131] | II, single arm | 70 R/R AML (25 HMA-naïve and 45 HMA-failure) | Nivolumab 3 mg/kg on day 1 and day 14, plus AZA 75 mg/m2 daily for 7 days, Q4-6 weeks | PD- 1 + HMA | ORR 33% (58% in HMA-naïve,22% in HMA-failure patients); CR/CRi was 22%; mOS 6.3 mos | 23% grade > 2 immune toxicities, 9 pneumonitis, 6 nephritis, 3 immune related skin rash, and 2 transaminitis |
Gerds, et al. [129] | Ib, multi-arm non-randomized | 10 HMA-failure MDS | Atezolizumab 1200 mg Q3weeks | PD-L1 | ORR 0%; CR 0%; mOS 5.9 mos | 10% grade > 3 FN; 0% died (10% occurred within 3 months) |
11 HMA-failure MDS | Atezolizumab 1200 mg Q3weeks plus AZA 75 mg/m2 daily for 7 days Q4weeks | PD-L1 + HMA | ORR 9%; CR 0%; mOS 10.7 mos | 36% grade > 3 FN; 64% died (18% occurred within 3 months) | ||
21 treatment-naïve MDS | Atezolizumab 840 mg Q2weeks plus AZA 75 mg/m2 daily for 7 days Q4weeks | PD-L1 + HMA | ORR 62%; CRp 14%; mOS NR | 33% grade > 3 FN; 29% died (all occurred within 3 months) | ||
Zeidan, et al. [134] | II, multi-arms randomized controlled | 42 treatment-naïve MDS | Durvalumab 1500 mg Q4weeks plus AZA 75 mg/m2 daily for 7 days Q4weeks | PD-L1 + HMA | ORR 61.9%; CR 7.1%; mOS 11.6 mos | Most common treatment-emergent AEs were hematologic and gastrointestinal toxicity. Immune-mediated AEs were observed in 7 MDS and 17 AML patients |
42 treatment-naïve MDS | AZA 75 mg/m2 daily for 7 days Q4weeks | HMA | ORR 47.6%; CR 9.5%; mOS 16.7 mos; | |||
64 treatment-naïve AML 1–7 every 4 weeks | Durvalumab 1500 mg Q4weeks plus AZA 75 mg/m2 daily for 7 days Q4weeks | PD-L1 + HMA | ORR 31.3%; CR 17.2%; mOS 13.0 mos | |||
65 treatment-naïve AML | AZA 75 mg/m2 daily for 7 days Q4weeks | HMA | ORR 35.4%; CR 21.5%; mOS 14.4 mos | |||
Zeidner et al. [136] | II, single arm | 37 R/R AML | HiDAC 1.5/2 gm/m2 daily for 5 days plus Pembrolizumab 200 mg on day 14. Responders were continued to receive pembrolizumab 200 mg Q3weeks | PD-1 +  chemotherapy | ORR 46%; CR 38%; mOS 8.9 mos | Most frequent grade > 3 pembrolizumab-related toxicities were ALT elevation (n = 1), AST elevation (n = 1), and grade > 3 maculopapular rash (n = 2). One patient did not survive due to disease progression within sixty days |
Ravandi et al. [137] | II, single arm | 44 treatment-naïve (42 AML and 2 high-risk MDS) | cytarabine 1.5 g/m2 daily for 4 days and idarubicin 12 mg/m2 daily for 3 days, plus Nivolumab 3 mg/kg on day 24 ± 2 and continued Q2weeks | PD-1 +  chemotherapy | ORR 80%; CR 78%; mOS 18.54 mos | 6 patients had seven grade 3/4 IRAE with rash (n = 2), colitis (n = 2), transaminitis (n = 1), pancreatitis (n = 1) and cholecystitis (n = 1) |