Table 1 CTLA-4 and PD-1 inhibitors in hematologic malignancies

NCT01822509

I

28

Post allo-SCT relapsed HM

AML (16), leukemia cutis (3), myeloid sarcoma (1), HL (7), NHL (4), MDS (2), MM, MPN, ALL (1 each)

Ipilimumab

ORR/CR/PR/SD: 32%/23%/9%/27%

[31]

NCT02397720

II

70

RR AML

2°AML (44%), adverse risk CG (34%), TP53 (16 patients)

Nivolumab + azacytidine

ORR/CR/PR/HI/SD: 33%/22%/1.4%/10%/8.5%

[32]

14

RR AML in 1st or 2nd relapse

2°AML (36%), adverse CG (25%), TP53 (5 patients)

Nivolumab + ipilimumab + azacytidine

ORR/CR/SD: 43%/43%/14%

[32]

NCT02532231

II

14

High-risk AML in CR, ineligible for SCT

Adverse CG (29%), TP53 (3 patients)

Nivolumab maintenance

CRd: 71% at 12 months

12 and 18 months OS: 86% and 67%, respectively

[33]

NCT02768792

II

26

RR AML

2°AML (38%), adverse CG (46%)

Pembrolizumab + cytarabine

ORR/CR/PR: 42%/35%/45%

MRD: 5/9 patients in CR

[34]

NCT02464657

I/II

44

Newly diagnosed AML and MDS

De novo AML (32), 2°AML (7), t-AML (3), high-risk MDS (2)

Adverse CG (29%), TP53 (8 patients)

Idarubicin, cytarabine + nivolumab

CR/CRi: 77%

MRD negative: 18/34 patients in CR

[35, 36]

CheckMate-039

I

23

RR HL

Nodular sclerosing (22), mixed cellularity (1), 78% relapse after SCT/BV

Nivolumab

ORR/CR/PR/SD: 87%/17%/70%/13%

86% PFS rate at 24 weeks

7/20 responses lasted > 1.5 years

[37, 38]

81

RR NHL

FL (10), DLBCL (11), MF (13), PTCL (5), MM (27), other B-NHL (10), T-NHL (5)

Nivolumab

ORR/CR/PR/SD

FL: 40%/10%/30%/60%

DLBCL: 36%/18%/18%/27%

MF: 15%/0%/15%/69%

PTCL: 40%/0/40%/0

MM: 4%/0/0/63%

Other B-NHLs: 0/0/0/70%

T NHL: 0/0/0/20%

[39]

65

RR NHL

HL (31), MM (17), PMBCL (1), B-NHL (15),

T-NHL (11)

Nivolumab + ipilimumab

ORR/CR/PR/SD

HL: 74%/19%/55%/10%

MM: 0/0/0/1

B- NHL: 20%/0/20%/7%

T-NHL: 9%/0/9%/36%

[40]

CheckMate-205

243

RR HL

Cohort 1: brentuximab vedotin naïve (63)

Cohort 2: brentuximab vedotin after auto-SCT (80)

Cohort 3: brentuximab vedotin before and or after auto-SCT (100)

Nivolumab

ORR/CR/PR/SD

Overall: 69%/16%/53%/19%

Cohort 1: 65%/29%/37%/24%

Cohort 2: 68%/13%/55%/21%

Cohort 3: 73%/12%/61%/15%

[41, 42]

KEYNOTE-13

I

31

RR HL

Post brentuximab vedotin relapse (100%)

Post auto-SCT (71%)

Pembrolizumab

ORR/CR/PR/SD: 65%/16%/48%/23%

[43]

21

RR PBMCL

SCT ineligible (62%)

Pembrolizumab

ORR/CR: 48%/33%

[44]

KEYNOTE-087

II

210

RR HL

Cohort 1: auto-SCT and brentuximab vedotin (69)

Cohort 2: salvage CT + brentuximab vedotin (81)

Cohort 3: auto-SCT only (60)

Pembrolizumab

ORR/CR/PR: 72%/28%/44%

ORR/CR:

Cohort 1: 77%/26%

Cohort 2: 67%/26%

Cohort 3: 73%/32%

[45, 46]

KEYNOTE-170

II

53

RR PBMCL

Auto-SCT ineligible (74%)

Pembrolizumab

ORR/CR: 45%/13%

[44]

NCT02572167

I/II

62

RR HL

Pembrolizumab + brentuximab vedotin

ORR/CR/PR/SD: 82%/61%/21%/8%

[47]

ECOG-ACRIN E4412

I

22

RR HL

Nivolumab + ipilimumab + brentuximab vedotin

ORR/CR: 82%/68%

[48]