GRADE summary of findings for efficacy outcomes
| Quadruplet vs triplet therapy for patients with NDMM . | ||||||
|---|---|---|---|---|---|---|
| Outcomes . | Anticipated absolute effects∗ (95% CI) . | Relative effect (95% CI) . | No. of participants (studies) . | Certainty of the evidence (GRADE) . | Comments . | |
| Risk with triplets . | Risk with quadruplets . | |||||
| ORR | 897/1000 | 924/1000 (906-942) | RR, 1.03 (1.01-1.05) | 3405 (6 studies) | ⨁⨁⨁⨁ High† | Induction quadruplet therapy increases ORR slightly, compared with triplet induction therapy. |
| CR+ | 516/1000 | 625/1000 (563-692) | RR, 1.21 (1.09-1.34) | 3047 (6 studies) | ⨁⨁⨁⨁ High†,‡ | Induction quadruplet therapy increases the rate of CR+ compared with triplet induction therapy. |
| sCR | 363/1000 | 476/1000 (374-607) | RR, 1.31 (1.03-1.67) | 2294 (4 RCTs) | ⨁⨁⨁ˆ Moderate†,§ | Induction quadruplet therapy likely increases the rate of stringent CR compared with triplet induction therapy. |
| MRD 10–5 negativity | 462/1000 | 642/1000 (568-730) | RR, 1.39 (1.23-1.58) | 3716 (7 studies) | ⨁⨁⨁ˆ Moderate‡,|| | Induction quadruplet therapy likely results in an increase in MRD 10–5 negativity rates compared with triplet induction therapy. |
| MRD 10–6 negativity | 347/1000 | 562/1000 (472-674) | RR, 1.62 (1.36-1.94) | 2857 (6 studies) | ⨁⨁⨁ˆ Moderate|| | Induction quadruplet therapy likely results in a large increase in MRD 10–6 negativity rates compared with triplet induction therapy. |
| Sustained MRD negativity | 276/1000 | 561/1000 (453-691) | RR, 2.03 (1.64-2.50) | 2447 (4 studies) | ⨁⨁⨁ˆ Moderate‡,|| | Induction quadruplet therapy likely results in a large increase in sustained MRD 10–5 negativity rates compared with triplet induction therapy. |
| PFS | NA | NA | HR, 0.55 (0.46-0.66) | 2447 (4 studies) | ⨁⨁⨁⨁ High | Induction quadruplet therapy results in large increase in PFS compared with triplet induction therapy. |
| OS | NA | NA | HR, 0.65 (0.53-0.79) | 2447 (4 studies) | ⨁⨁ˆˆ Low¶ | Induction quadruplet therapy may result in an increase in OS compared with triplet induction therapy. |
| Quadruplet vs triplet therapy for patients with NDMM . | ||||||
|---|---|---|---|---|---|---|
| Outcomes . | Anticipated absolute effects∗ (95% CI) . | Relative effect (95% CI) . | No. of participants (studies) . | Certainty of the evidence (GRADE) . | Comments . | |
| Risk with triplets . | Risk with quadruplets . | |||||
| ORR | 897/1000 | 924/1000 (906-942) | RR, 1.03 (1.01-1.05) | 3405 (6 studies) | ⨁⨁⨁⨁ High† | Induction quadruplet therapy increases ORR slightly, compared with triplet induction therapy. |
| CR+ | 516/1000 | 625/1000 (563-692) | RR, 1.21 (1.09-1.34) | 3047 (6 studies) | ⨁⨁⨁⨁ High†,‡ | Induction quadruplet therapy increases the rate of CR+ compared with triplet induction therapy. |
| sCR | 363/1000 | 476/1000 (374-607) | RR, 1.31 (1.03-1.67) | 2294 (4 RCTs) | ⨁⨁⨁ˆ Moderate†,§ | Induction quadruplet therapy likely increases the rate of stringent CR compared with triplet induction therapy. |
| MRD 10–5 negativity | 462/1000 | 642/1000 (568-730) | RR, 1.39 (1.23-1.58) | 3716 (7 studies) | ⨁⨁⨁ˆ Moderate‡,|| | Induction quadruplet therapy likely results in an increase in MRD 10–5 negativity rates compared with triplet induction therapy. |
| MRD 10–6 negativity | 347/1000 | 562/1000 (472-674) | RR, 1.62 (1.36-1.94) | 2857 (6 studies) | ⨁⨁⨁ˆ Moderate|| | Induction quadruplet therapy likely results in a large increase in MRD 10–6 negativity rates compared with triplet induction therapy. |
| Sustained MRD negativity | 276/1000 | 561/1000 (453-691) | RR, 2.03 (1.64-2.50) | 2447 (4 studies) | ⨁⨁⨁ˆ Moderate‡,|| | Induction quadruplet therapy likely results in a large increase in sustained MRD 10–5 negativity rates compared with triplet induction therapy. |
| PFS | NA | NA | HR, 0.55 (0.46-0.66) | 2447 (4 studies) | ⨁⨁⨁⨁ High | Induction quadruplet therapy results in large increase in PFS compared with triplet induction therapy. |
| OS | NA | NA | HR, 0.65 (0.53-0.79) | 2447 (4 studies) | ⨁⨁ˆˆ Low¶ | Induction quadruplet therapy may result in an increase in OS compared with triplet induction therapy. |
OR, odds ratio.
Boldface values indicate statistical significance and relevance to the overall findings of the study.
The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
Some concern with missing information especially from abstracts but not enough to rate down.
Despite heterogeneity, all studies were on the side of benefit.
Visual inconsistency and statistical tests for heterogeneity were significant.
Risk of bias from missing data was significant.
Small number of events.