Chemotherapeutic options in chronic lymphocytic leukemia: a meta-analysis of the randomized trials
Phase meta-analysis
- Population
- Patients with chronic lymphocytic leukemia in randomised trials of the timing and intensity of initial chemotherapy; 2048 patients with early disease (six trials) and 2022 patients (ten trials) in the combination-versus-chlorambucil comparison.
- Design
- Collaborative meta-analysis with centralised review of data for each patient from all relevant randomised trials, published or not. Two comparisons: immediate versus deferred chemotherapy (chlorambucil or chlorambucil plus prednis(ol)one) in early-stage disease (six trials), and combination chemotherapy (for example COP or CHOP) versus single-agent chlorambucil, with or without prednis(ol)one, in more advanced disease (ten trials).
- Arms
- Immediate chemotherapy (experimental): Immediate chlorambucil-based chemotherapy
- Deferred chemotherapy (control): Deferred chemotherapy
- Combination chemotherapy (experimental): Combination chemotherapy (for example COP or CHOP)
- Chlorambucil (control): Single-agent chlorambucil, with or without prednis(ol)one
- People
- CLL Trialists' Collaborative Group, CLL Trialists' Collaborative Group
Δ 120-month OS−3 pointsΔ 60-month OS0 points
Show the numbers
| Endpoint | Analysis | Immediate chemotherapy / Combination chemotherapy | Deferred chemotherapy / Chlorambucil | Effect |
|---|---|---|---|---|
| OSEarly-stage disease, six trials (2048 patients) | primaryCLL 1999 | 44% at 10 y | 47% at 10 y | Difference -3% (95% CI -10% to 4%); not statistically significant. |
| OSMore advanced disease, ten trials (2022 patients) | primaryCLL 1999 | 48% at 5 y | 48% at 5 y | Difference 0% (95% CI -6% to 5%). For the six trials with an anthracycline-containing regimen: 325 deaths among 627 patients versus 306 among 636 with chlorambucil; death rate ratio 1.07 (95% CI 0.91-1.25), not statistically significant. |
| Endpoint | Analysis | Immediate chemotherapy / Combination chemotherapy | Deferred chemotherapy / Chlorambucil | Effect |
|---|---|---|---|---|
| OSEarly-stage disease, six trials (2048 patients) | primaryCLL 1999 | 44% at 10 y | 47% at 10 y | Difference -3% (95% CI -10% to 4%); not statistically significant. |
| OSMore advanced disease, ten trials (2022 patients) | primaryCLL 1999 | 48% at 5 y | 48% at 5 y | Difference 0% (95% CI -6% to 5%). For the six trials with an anthracycline-containing regimen: 325 deaths among 627 patients versus 306 among 636 with chlorambucil; death rate ratio 1.07 (95% CI 0.91-1.25), not statistically significant. |