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multiple myeloma - 2nd line (L2), pembrolizumab based treatment , meta-analysis of study results

Outcome Relative effect 95%CI LoD Trt. better when I2 k (RCT/OBS) Bayesian probability Overall ROB Publication bias Degree of certainty Endpoint importance Published MA

efficacy endpoints 00

deaths (OS) 1.61 [0.91, 2.85]< 10%1 study (1/-)5.1 %NAnot evaluable crucial-
progression or deaths (PFS) 1.53 [1.05, 2.22]< 10%1 study (1/-)1.3 %NAnot evaluable important-
DCR 1.01 [0.51, 2.01]> 10%1 study (1/-)51.1 %NAnot evaluable non important-
objective responses (ORR) 0.78 [0.46, 1.30]> 10%1 study (1/-)16.7 %NAnot evaluable non important-

safety endpoints 00

AE (any grade) 5.13 [0.59, 44.58]< 10%1 study (1/-)7.0 %NAnot evaluable non important-
AE (grade 3-4) 1.71 [0.98, 2.99]< 10%1 study (1/-)2.9 %NAnot evaluable non important-
AE leading to death (grade 5) 4.78 [1.33, 17.23]< 10%1 study (1/-)0.9 %NAnot evaluable non important-
SAE (any grade) 1.93 [1.16, 3.23]< 10%1 study (1/-)0.6 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Hepatitis TRAE (grade 3-4) 2.03 [0.07, 60.94]< 10%1 study (1/-)34.4 %NAnot evaluable non important-
Hyperthyroidism TRAE (grade 3-4) 1.01 [0.02, 51.24]< 10%1 study (1/-)49.8 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 1.01 [0.02, 51.24]< 10%1 study (1/-)49.8 %NAnot evaluable non important-
Infusion-related reactions TRAE (grade 3-4) 1.01 [0.02, 51.24]< 10%1 study (1/-)49.8 %NAnot evaluable non important-
Myocarditis TRAE (grade 3-4) 1.01 [0.02, 51.24]< 10%1 study (1/-)49.8 %NAnot evaluable non important-
Pneumonitis TRAE (grade 3-4) 2.03 [0.07, 60.94]< 10%1 study (1/-)34.4 %NAnot evaluable non important-
Rash TRAE (grade 3-4) 6.18 [0.31, 124.71]< 10%1 study (1/-)12.0 %NAnot evaluable non important-
Stevens-Johnson syndrome TRAE (grade 3-4) 1.01 [0.02, 51.24]< 10%1 study (1/-)49.8 %NAnot evaluable non important-

AE (grade 3-4) endpoints 00

Anaemia AE (grade 3-4) 1.31 [0.64, 2.68]< 10%1 study (1/-)22.7 %NAnot evaluable non important-
Asthenia AE (grade 3-4) 0.16 [0.01, 3.32]< 10%1 study (1/-)87.8 %NAnot evaluable non important-
Back pain AE (grade 3-4) 0.10 [0.01, 1.80]< 10%1 study (1/-)93.9 %NAnot evaluable non important-
Constipation AE (grade 3-4) 2.03 [0.07, 60.94]< 10%1 study (1/-)34.4 %NAnot evaluable non important-
Cough AE (grade 3-4) 0.50 [0.02, 15.11]< 10%1 study (1/-)65.2 %NAnot evaluable non important-
Diarrhoea AE (grade 3-4) 1.01 [0.14, 7.28]< 10%1 study (1/-)49.7 %NAnot evaluable non important-
Dizziness AE (grade 3-4) 2.03 [0.07, 60.94]< 10%1 study (1/-)34.4 %NAnot evaluable non important-
Dyspnoea AE (grade 3-4) 0.33 [0.03, 3.22]< 10%1 study (1/-)82.8 %NAnot evaluable non important-
Fatigue AE (grade 3-4) 0.05 [0.00, 0.80]< 10%1 study (1/-)98.2 %NAnot evaluable non important-
Headache AE (grade 3-4) 1.01 [0.02, 51.24]< 10%1 study (1/-)49.8 %NAnot evaluable non important-
Increased ALT AE (grade 3-4) 3.13 [0.62, 15.84]< 10%1 study (1/-)8.4 %NAnot evaluable non important-
Nausea AE (grade 3-4) 0.50 [0.02, 15.11]< 10%1 study (1/-)65.2 %NAnot evaluable non important-
Neutropenia AE (grade 3-4) 1.90 [1.07, 3.37]< 10%1 study (1/-)1.5 %NAnot evaluable non important-
Peripheral oedema AE (grade 3-4) 0.50 [0.02, 15.11]< 10%1 study (1/-)65.2 %NAnot evaluable non important-
Pneumonia AE (grade 3-4) 1.09 [0.51, 2.31]< 10%1 study (1/-)41.4 %NAnot evaluable non important-
Pyrexia AE (grade 3-4) 0.25 [0.03, 2.23]< 10%1 study (1/-)89.2 %NAnot evaluable non important-
Thrombocytopenia AE (grade 3-4) 1.87 [0.75, 4.63]< 10%1 study (1/-)8.9 %NAnot evaluable non important-

LoD: level of statistical demonstration: Statistically conclusive: statistically significant with a strict control of overall risk of type 1 error (statistically demonstrated), does not take into account the risk of bias; suggested: nominally statistically significant but without a strict control of overall risk of type 1 error; inconclusive: not nominally statistically significant; safety concerns;
Bayesian probability: Bayesian posterior probability of treatment effect (computed with a noninformative prior); ROB: risk of bias; k: number of studies; published MA: number of published meta-analysis on the same topic; degree of certainty adapted from GRADE. Trt. better when: indicates when the relative treatment effect shows that the studied treatment is better than control.