Edited by: Shuang Zhou, University of Houston, United States
Reviewed by: Marc Henri De Longueville, UCB Pharma, Belgium; Pooja Dhupkar, University of Texas MD Anderson Cancer Center, United States
This article was submitted to Pharmaceutical Medicine and Outcomes Research, a section of the journal Frontiers in Pharmacology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor mainly expressed on activated T cells, natural killer cells, and B cells (Ishida et al.,
Combination chemotherapy can cure most patients with classic Hodgkin lymphomas (cHL). However, for patients who failed to treatment (refractory cHL) or regained the disease soon (relapsed cHL), immunotherapy can be an appropriate option. CHL's typical feature is the existence of the malignant Hodgkin Reed Sternberg (HRS) cells surrounded by an inflammatory immune infiltrate. Meanwhile, PD-L1 expression was upregulated in cHL via JAK2-STAT signaling with near universal genetic amplification of the 9p24.1 locus (Green et al.,
The US Food and Drug Administration (FDA) currently approved two anti-PD-1 antibodies, including pembrolizumab and nivolumab. Pembrolizumab is a fully humanized IgG4 kappa isotype anti-PD-1 monoclonal antibody. Nivolumab is a fully human IgG4 anti-PD-1 monoclonal antibody. Clinic trials with other anti-PD-1 antibodies and anti-PD-L1 antibodies are ongoing, the results have not been publicated.
In recent years, immunotherapy with PD-1 blockage or PD-L1 blockage were successfully used in many cancers, including melanoma, non-small cell lung cancer, renal cell carcinoma, ovarian cancer, lymphoma, et al. (Sunshine and Taube,
We obeyed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We searched PUBMED, EMBASE, and The Cochrane Library to identify the relevant studies up to March 2018. We used a combination of terms: “pembrolizumab/ lambrolizumab/ Keytruda/ MK-3475” OR “Nivolumab/ MDX-1106/ ONO-4538/ BMS-936558/ Opdivo” AND “lymphoma.”
Studies had to meet the following criteria: (1) prospective trials concerning the efficacy or safety of nivolumab/pembrolizumab on patients with relapsed or refractory lymphoma. (2) articles reporting any of the data: ORR, 6-month PFS rate, 6-month OS rate, and drug-related AEs.
Exclusion criteria: (1) articles not association with our topics; (2) studies without usable data; and (3) retrospective or observed studies, letters, editorials, case reports, and reviews.
The eligible studies were reviewed and extracted data by two authors independently. We extracted first author, published year, ClinicalTrials.gov number, phase, study design, treatment, disease, number of patients, age, prior systemic treatment regimens, ORR, 6-month PFS rate, 6-month OS rate, any grade AEs, grader ≥3 AEs, and drug-related deaths. The methodological index for non-randomized studies (MINORS) (Slim et al.,
The primary outcome for efficacy was ORR; secondary outcomes were 6-month PFS and 6-month OS. For safety analysis, the incidence and exhibition of any grade and grade ≥3 AEs were evaluated. In each trial, objective response rate (ORR) = [(complete responses + partial responses) ÷ total no. of patients] × 100. Heterogeneity among studies was detected with a forest plot and the inconsistency statistic (I2). A random-effect model was used when potential heterogeneity existed (I2 >50%); otherwise, the fixed-effect model was employed. The Metaprop module in the R-3.3.2 statistical software package was used to analyze the efficacy and safety. Subgroup analysis was performed to solve heterogeneity. Sensitivity analysis was carried out by using different effect models. No dose effect was considered.
The search strategy produced a total of 443 records; 41 studies were removed after duplication; 391 studies were excluded. Finally, ten studies were enrolled after removing one study with combined therapy (Ansell et al.,
The flow chart.
The characteristics of included studies.
1 | Lesokhin et al. ( |
NCT01592370 | I | dose-escalation, cohort-expansion | nivolumab, 1 or 3 mg/kg every 2 weeks | relapsed or refractory NHL/MM | 82:27 MM;31 B-NHL; 23 T-NHL; 1 CML | MM: 63(32–81) B-NHL: 65(23–74) T-NHL:61(30–81) | 3(1–12) | 51 | 18 | 1(pneumonitis/ARDS) | 3.70%; 22.22%; 0 | – | – |
2 | Ansell et al. ( |
NCT01592370 | I | dose-escalation, cohort-expansion | nivolumab, 1 or 3 mg/kg every 2 weeks | relapsed or refractory HL | 23 | 35(20–54) | – | 18 | 5 | 0 | 87% | 86% | – |
3 | Maruyama et al. ( |
JapicCTI-142755 | II | multicenter, single-arm | nivolumab, 3 mg/kg every 2 weeks | relapsed or refractory HL | 17 | 63(29–83) | 3 (2–5) | 17 | 4 | 0 | 75% | 60% | 100% |
4 | Younes et al. ( |
NCT02181738 | II | multicentre, multicohort, single-arm | nivolumab, 3 mg/kg every 2 weeks | relapsed or refractory HL | 80 | 37 (28–48) | 4 (4–7) | 71 | 20 | 0 | 66% | 77% | 99% |
5 | Armand et al. ( |
CheckMate 205 | II | multicohort, single-arm | nivolumab 3 mg/kg every 2 weeks | relapsed/refractory cHL | 243 | – | – | – | – | 0 | 69% | – | – |
1 | Armand et al. ( |
NCT01953692 | Ib | multicohort | pembrolizumab, 10 mg/kg every 2 weeks | relapsed or refractory HL | 31 | 32(20–67) | – | 21 | 5 | 0 | 65% | 69% | 100% |
2 | Chen et al. ( |
NCT02453594 | II | multicenter single-arm | pembrolizumab, 200 mg once every 3 weeks | relapsed/refractory HL | 210 | 35(18–76) | 4(1–12) | – | – | 0 | 69% | 72.40% | 99.50% |
3 | Ding et al. ( |
NCT02332980 | II | single-arm | pembrolizumab, 200 mg every 3 weeks | relapsed and transformed CLL | 25: 16 relapsed or refractory CLL; 9 RT | 69(46–81) | 4(1–10) | 25 | 15 | 1(Pseudomonas sepsis) | 0; 44% | – | 57.14%; 71.43% |
4 | Zinzani et al. ( |
NCT01953692 | Ib | multicenter, international, multicohort | pembrolizumab, 10 mg/kg every 2 weeks(10); 200 mg every 3 weeks(8) | relapsed/refractory primary mediastinal large B-cell lymphoma (rrPMBCL) | 18 | 30(22–62) | 4(2–6) | 11 | 2 | 0 | 41% | – | – |
5 | Zinzani P. L. et al. ( |
NCT02576990 | II | two -cohort, multicenter | pembrolizumab 200 mg IV every 3 weeks | relapsed/refractory primary mediastinal large B-cell lymphoma (rrPMBCL) | 33 | 32(20–58) | 3(1–5) | 19 | 6 | 0 | 35% | – | – |
Overall eight studies were included to assess the pooled incidence of any grade (74%, 95%CL: 62%−84%) and grade ≥3 (24%, 95%CL: 17%−34%) AEs (
The forest plot of pooled incidence of AEs in any grade
The incidence of adverse events in all grade or grade ≥3.
Fatigue | Nivolumab | 4 | 40 | 202 | 0.2018 [0.1514; 0.2636] | Fixed | 4 | 0 | 202 | 0.0121 [0.0030; 0.0471] | Fixed | 0.2200 | |
Pembrolizumab | 4 | 28 | 284 | 0.1024 [0.0715; 0.1445] | Fixed | 3 | 3 | 253 | 0.0280 [0.0044; 0.1595] | Random | |||
Overall | 8 | 68 | 486 | 0.1491 [0.1027; 0.2113] | Random | 7 | 3 | 455 | 0.0245 [0.0113; 0.0524] | Fixed | |||
Pyrexia | Nivolumab | 3 | 16 | 122 | 0.1675 [0.0486; 0.4422] | Random | 0.442 | 3 | 1 | 122 | 0.0367 [0.0105; 0.1199] | Fixed | 0.49 |
Pembrolizumab | 3 | 26 | 253 | 0.1030 [0.0711; 0.1471] | Fixed | 3 | 2 | 253 | 0.0208 [0.0073; 0.0579] | Fixed | |||
Overall | 6 | 42 | 375 | 0.1300 [0.0728; 0.2213] | Random | 6 | 3 | 375 | 0.0263 [0.0118; 0.0575] | Fixed | |||
Chills | Pembrolizumab | 3 | 9 | 266 | 0.0386 [0.0202; 0.0727] | Fixed | 2 | 0 | 235 | 0.0067 [0.0009; 0.0463] | Fixed | ||
Asthenia | Pembrolizumab | 2 | 5 | 241 | 0.0288 [0.0064; 0.1199] | Random | 1 | 1 | 33 | 0.0303 | |||
Pneumonitis | Nivolumab | 2 | 12 | 162 | 0.0629 [0.0129; 0.2571] | Random | 0.859 | 2 | 5 | 162 | 0.0370 [0.0155; 0.0860] | Fixed | 0.853 |
Pembrolizumab | 2 | 4 | 49 | 0.0840 [0.0319; 0.2037] | Fixed | 1 | 1 | 33 | 0.0303 | ||||
Overall | 4 | 15 | 211 | 0.0942 [0.0574; 0.1508] | Fixed | 3 | 6 | 195 | 0.0358 [0.0161; 0.0775] | Fixed | |||
Embolism | Nivolumab | 2 | 1 | 162 | 0.0138 [0.0035; 0.0535] | Fixed | 2 | 1 | 162 | 0.0138 [0.0035; 0.0535] | Fixed | ||
Cough | Nivolumab | 1 | 2 | 23 | 0.0879 | 1 | 0 | 23 | 0 | ||||
Pembrolizumab | 2 | 19 | 235 | 0.1297 [0.0236; 0.4793] | Random | 2 | 1 | 235 | 0.0091 [0.0023; 0.0357] | Fixed | |||
Overall | 3 | 21 | 258 | 0.1156 [0.0346; 0.3226] | Random | 3 | 1 | 258 | 0.0107 [0.0031; 0.0364] | Fixed | |||
Upper respiratory tract infection | Nivolumab | 2 | 5 | 97 | 0.0603 [0.0010; 0.8038] | Random | 2 | 0 | 97 | 0.0130 [0.0018; 0.0871] | Fixed | ||
Pembrolizumab | 1 | 13 | 210 | 0.0619 | 1 | 0 | 210 | 0 | |||||
Overall | 3 | 18 | 307 | 0.0780 [0.0147; 0.3243] | Random | 3 | 0 | 307 | 0.0074 [0.0015; 0.0358] | Fixed | |||
Dyspnea | Nivolumab | 1 | 3 | 80 | 0.0375 | 1 | 1 | 80 | 0.0125 | ||||
Pembrolizumab | 3 | 17 | 266 | 0.0951 [0.0172; 0.3873] | Random | 2 | 6 | 235 | 0.0424 [0.0024; 0.4524] | Random | |||
Overall | 4 | 20 | 346 | 0.0764 [0.0202; 0.2489] | Random | 3 | 7 | 315 | 0.0298 [0.0036; 0.2068] | Random | |||
Rash | Nivolumab | 4 | 35 | 202 | 0.1927 [0.1146; 0.3057] | Random | 4 | 5 | 202 | 0.0366 [0.0175; 0.0749] | Fixed | 0.651 | |
Pembrolizumab | 2 | 18 | 235 | 0.0766 [0.0488; 0.1183] | Fixed | 2 | 1 | 235 | 0.0145 [0.0006; 0.2577] | Random | |||
Overall | 6 | 53 | 437 | 0.1480 [0.0869; 0.2408] | Random | 6 | 6 | 437 | 0.0338 [0.0176; 0.0639] | Fixed | |||
Pruritus | Nivolumab | 4 | 24 | 202 | 0.1403 [0.0707; 0.2593] | Random | 4 | 0 | 202 | 0.0121 [0.0030; 0.0471] | Fixed | ||
Pembrolizumab | 1 | 8 | 210 | 0.0381 | 1 | 0 | 210 | 0 | |||||
Overall | 5 | 32 | 412 | 0.1081 [0.0509; 0.2152] | Random | 5 | 0 | 412 | 0.0087 [0.0025; 0.0296] | Fixed | |||
Decreased appetite | Nivolumab | 2 | 9 | 162 | 0.0532 [0.0160; 0.1621] | Random | 0.645 | 2 | 0 | 162 | 0.0061 [0.0009; 0.0420] | Fixed | |
Pembrolizumab | 2 | 4 | 49 | 0.0844 [0.0320; 0.2045] | Fixed | 1 | 0 | 18 | 0 | ||||
Overall | 4 | 13 | 211 | 0.0701 [0.0410; 0.1172] | Fixed | 3 | 0 | 180 | 0.0099 [0.0020; 0.0476] | Fixed | |||
Diarrhea | Nivolumab | 4 | 19 | 202 | 0.0959 [0.0620; 0.1455] | Fixed | 0.9710 | 4 | 0 | 202 | 0.0121 [0.0030; 0.0471] | Fixed | 0.853 |
Pembrolizumab | 4 | 26 | 284 | 0.0969 [0.0667; 0.1387] | Fixed | 3 | 2 | 253 | 0.0142 [0.0050; 0.0398] | Fixed | |||
Overall | 8 | 45 | 486 | 0.0965 [0.0727; 0.1269] | Fixed | 7 | 2 | 455 | 0.0134 [0.0058; 0.0306] | Fixed | |||
Nausea | Nivolumab | 2 | 13 | 103 | 0.1262 [0.0747; 0.2054] | Fixed | 0.305 | 2 | 0 | 103 | 0.0113 [0.0016; 0.0761] | Fixed | 0.958 |
Pembrolizumab | 4 | 23 | 284 | 0.1069 [0.0547; 0.1983] | Random | 3 | 0 | 253 | 0.0106 [0.0021; 0.0509] | Fixed | |||
Overall | 6 | 36 | 387 | 0.1016 [0.0741; 0.1380] | Fixed | 5 | 0 | 356 | 0.0109 [0.0031; 0.0369] | Fixed | |||
Vomiting | Nivolumab | 1 | 6 | 80 | 0.0750 | 1 | 0 | 80 | 0 | ||||
Pembrolizumab | 3 | 13 | 266 | 0.0533 [0.0311; 0.0899] | Fixed | 2 | 0 | 235 | 0.0067 [0.0009; 0.0463] | Fixed | |||
Overall | 4 | 19 | 346 | 0.0594 [0.0381; 0.0913] | Fixed | 3 | 0 | 315 | 0.0065 [0.0013; 0.0318] | Fixed | |||
Constipation | Nivolumab | 2 | 7 | 97 | 0.0746 [0.0359; 0.1484] | Fixed | 0.134 | 2 | 0 | 97 | 0.0130 [0.0018; 0.0871] | Fixed | |
Pembrolizumab | 2 | 8 | 241 | 0.0349 [0.0175; 0.0683] | Fixed | 1 | 0 | 210 | 0 | ||||
Overall | 4 | 15 | 338 | 0.0495 [0.0300; 0.0807] | Fixed | 3 | 0 | 307 | 0.0074 [0.0015; 0.0358] | Fixed | |||
Stomatitis | Nivolumab | 2 | 4 | 105 | 0.0456 [0.0171; 0.1157] | Fixed | 2 | 2 | 105 | 0.0229 [0.0057; 0.0873] | Fixed | ||
Lipase increased | Nivolumab | 2 | 5 | 105 | 0.0514 [0.0215; 0.1179] | Fixed | 4 | 18 | 428 | 0.0454 [0.0288; 0.0710] | Fixed | ||
AST increased | Nivolumab | 1 | 4 | 80 | 0.0500 | 1 | 2 | 80 | 0.0250 | ||||
Pembrolizumab | 1 | 2 | 31 | 0.0645 | 1 | 1 | 31 | 0.0323 | |||||
Overall | 2 | 6 | 111 | 0.0544 [0.0246; 0.1159] | Fixed | 2 | 3 | 111 | 0.0272 [0.0088; 0.0810] | Fixed | |||
ALT increased | Nivolumab | 1 | 3 | 80 | 0.0375 | 2 | 9 | 323 | 0.0279 [0.0146; 0.0528] | Fixed | |||
Pembrolizumab | 1 | 2 | 31 | 0.0645 | 1 | 1 | 31 | 0.0323 | |||||
Overall | 2 | 5 | 111 | 0.0465 [0.0195; 0.1070] | Fixed | 3 | 10 | 354 | 0.0283 [0.0153; 0.0518] | Fixed | |||
Hypothyroidism | Nivolumab | 2 | 7 | 40 | 0.1789 [0.0493; 0.4780] | Random | 0.251 | 2 | 0 | 40 | 0.0241 [0.0034; 0.1520] | Fixed | 0.463 |
Pembrolizumab | 3 | 33 | 259 | 0.1279 [0.0924; 0.1745] | Fixed | 2 | 1 | 228 | 0.0098 [0.0025; 0.0385] | Fixed | |||
Overall | 5 | 40 | 299 | 0.1377 [0.1025; 0.1826] | Fixed | 4 | 1 | 268 | 0.0132 [0.0043; 0.0403] | Fixed | |||
Headache | Nivolumab | 2 | 6 | 97 | 0.0844 [0.0080; 0.5126] | Random | 2 | 0 | 97 | 0.0130 [0.0018; 0.0871] | Fixed | ||
Pembrolizumab | 1 | 13 | 210 | 0.0619 | 1 | 0 | 210 | 0 | |||||
Overall | 3 | 19 | 307 | 0.0768 [0.0246; 0.2155] | Random | 3 | 0 | 307 | 0.0074 [0.0015; 0.0358] | Fixed | |||
Back pain | Nivolumab | 2 | 4 | 97 | 0.0544 [0.0113; 0.2244] | Random | 2 | 0 | 97 | 0.0130 [0.0018; 0.0871] | Fixed | 0.669 | |
Pembrolizumab | 1 | 4 | 210 | 0.0190 | 2 | 1 | 241 | 0.0132 [0.0007; 0.2022] | Random | ||||
Overall | 3 | 8 | 307 | 0.0358 [0.0119; 0.1026] | Random | 4 | 1 | 338 | 0.0184 [0.0059; 0.0559] | Fixed | |||
Myalgia | Nivolumab | 2 | 8 | 97 | 0.0838 [0.0424; 0.1587] | Fixed | 2 | 0 | 97 | 0.0130 [0.0018; 0.0871] | Fixed | ||
Pembrolizumab | 1 | 5 | 210 | 0.0238 | 1 | 0 | 210 | 0 | |||||
Overall | 3 | 13 | 307 | 0.0552 [0.0216; 0.1343] | Random | 3 | 0 | 307 | 0.0074 [0.0015; 0.0358] | Fixed | |||
Arthralgia | Nivolumab | 1 | 11 | 80 | 0.1375 | 1 | 0 | 80 | 0.0062 | ||||
Pembrolizumab | 1 | 8 | 210 | 0.0381 | 1 | 1 | 210 | 0.0048 | |||||
Overall | 2 | 19 | 290 | 0.0742 [0.0201; 0.2388] | Random | 2 | 1 | 290 | 0.0069 [0.0017; 0.0270] | Fixed | |||
Anemia | Nivolumab | 2 | 8 | 162 | 0.0507 [0.0256; 0.0982] | Fixed | 0.955 | 2 | 3 | 162 | 0.0331 [0.0124; 0.0850] | Fixed | 0.945 |
Pembrolizumab | 2 | 11 | 235 | 0.0579 [0.0005; 0.8856] | Random | 2 | 5 | 235 | 0.0296 [0.0003; 0.7551] | Random | |||
Overall | 3 | 16 | 317 | 0.0576 [0.0098; 0.2741] | Random | 3 | 8 | 317 | 0.0292 [0.0046; 0.1631] | Random | |||
Neutropenia | Nivolumab | 2 | 10 | 162 | 0.0670 [0.0364; 0.1203] | Fixed | 0.649 | 3 | 12 | 405 | 0.0322 [0.0183; 0.0558] | Fixed | 0.243 |
Pembrolizumab | 3 | 14 | 253 | 0.0558 [0.0333; 0.0921] | Fixed | 4 | 14 | 286 | 0.0685 [0.0216; 0.1969] | Random | |||
Overall | 5 | 24 | 415 | 0.0602 [0.0407; 0.0883] | Fixed | 7 | 26 | 691 | 0.0479 [0.0234; 0.0953] | Random | |||
Lymphopenia | Nivolumab | 3 | 8 | 185 | 0.0474 [0.0239; 0.0921] | Fixed | 3 | 5 | 185 | 0.0276 [0.0115; 0.0647] | Fixed | ||
Platelet count decreased | Nivolumab | 2 | 5 | 103 | 0.0553 [0.0038; 0.4766] | Random | 2 | 0 | 103 | 0.0113 [0.0016; 0.0761] | Fixed | ||
Pembrolizumab | 1 | 11 | 25 | 0.4400 | 1 | 5 | 25 | 0.2000 | |||||
Overall | 3 | 16 | 128 | 0.1354 [0.0225; 0.5159] | Random | 3 | 5 | 128 | 0.0414 [0.0034; 0.3530] | Random | |||
Leukopenia | Nivolumab | 2 | 6 | 162 | 0.0390 [0.0176; 0.0841] | Fixed | 2 | 3 | 162 | 0.0331 [0.0124; 0.0850] | Fixed |
The pooled ORR, 6-month PFS rate and 6-month OS rate were performed to evaluate the efficacy of nivolumab or pembrolizumab treated lymphoma. We enrolled all ten studies to analyze ORR, five studies to evaluate PFS and five studies to assess OS. The pooled ORR, PFS rate and OS rate were 58% (95%Cl: 47%−69%), 73% (95%Cl: 68%−78%), and 96% (95%Cl: 92%−98%), respectively. There were no significant differences in ORR between patients' mean age >50 years (46%, 16%−79%) and < 50 years (62%, 50%−73%). PFS and OS between patients' mean age >50 and < 50 years did not analyze due to limitation numbers. Meanwhile, the ORR, PFS and OS between nivolumab and pembrolizumab had no significant differences. While, the ORR in patients with HL was higher than patients with NHL (69.08 vs. 30.77%,
The forest plot of pooled ORR
Two studies without full text can't evaluate totally. The two items including unbiased evaluation of endpoints and prospective calculation of the sample size were not reported. The overall score was high. Therefore, the overall quality of the included studies was satisfactory (
The scores of MINORS.
Lesokhin et al. ( |
2 | 2 | 2 | 2 | 0 | 2 | 2 | 0 | 12 |
Ansell et al. ( |
2 | 2 | 2 | 2 | 0 | 2 | 2 | 0 | 12 |
Maruyama et al. ( |
2 | 2 | 2 | 1 | 0 | 2 | 2 | 0 | 11 |
Younes et al. ( |
2 | 2 | 2 | 2 | 0 | 2 | 2 | 0 | 12 |
Armand et al. ( |
2 | – | – | 2 | – | 2 | – | – | 6 |
Armand et al. ( |
2 | 2 | 2 | 2 | 0 | 2 | 2 | 0 | 12 |
Chen et al. ( |
2 | 2 | 2 | 2 | 0 | 2 | 2 | 0 | 12 |
Ding et al. ( |
2 | 2 | 2 | 1 | 0 | 2 | 2 | 0 | 11 |
Zinzani et al. ( |
2 | 2 | 2 | 1 | 0 | 2 | 2 | 0 | 11 |
Zinzani P. L. et al. ( |
2 | – | – | 2 | – | – | – | – | 4 |
Anti-PD-1 antibodies are rapidly developed in recent decades. FDA has approved two anti-PD-1 antibodies, including pembrolizumab and nivolumab. However, the AEs may be different between pembrolizumab and nivolumab. Meanwhile, the efficacy of these two anti-PD-1 antibodies in lymphoma ranged widely.
This meta-analysis included overall ten prospective studies with 718 patients with lymphomas, including 114 patients with NHL and 604 patients with HL, to assess the safety and efficacy. The pooled incidence of AEs of any grade reached 74%, while grade ≥3 was only 24%. However, there were two patients occurred drug-related death. Approximately 58% of patients gained complete response or partial response. Meanwhile, 73% of patients' diseases remained stable for half a year, and 96% of patients survived for half a year.
Immune-related adverse events caused by blockage of the PD-1 pathway can affect almost any organ, mainly mediated by T cells (Weber et al.,
Many clinic trials reported fatigue as one of the AEs with anti-PD-1 antibodies (Brahmer et al.,
Arthritis, myositis, sicca syndrome, vasculitis were common AEs for anti-PD-1 antibodies in the type of rheumatology. Several studies suggested that patients with underlying autoimmunity, including rheumatic diseases, can be effectively treated by immune checkpoint inhibitors, but 1/3 of patients may occur the outbreak of underlying diseases (Johnson et al.,
Former study (Lee et al.,
Generally, the expression of PD-1 is usually elevated on tumor-infiltrating T cells (TILs) in lymphomas, especially observed in HL (Yamamoto et al.,
Previous study (Georgieva et al.,
Our study has several limitations. First, the study number was limited, which may make the data skewed. Second, there were only phase I/II studies without double-blinded RCT, which may lead the potential performance bias. Third, the survival time and PFS time didn't present individually, so we can't perform the survival analysis.
In conclusion, this meta-analysis demonstrated that nivolumab and pembrolizumab have potential effects of ORR, 6-month OS rate and 6-month PFS rate, while the AEs and drug-related deaths were tolerable in patients with relapsed or refractory lymphoma. We also demonstrated that pembrolizumab had a lower risk of AEs than nivolumab, and patients with HL had a better ORR than NHL. Further researches with these novel drugs are needed to compare with traditional therapy for patients with relapsed or refractory lymphoma.
HZ collected, analyzed the data and wrote the article. XF and QL collected data, prepared the pictures and tables. TN provided the idea and modified the article. All authors read and approved the final manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.