PFS and MRD in CLL8, CLL10, and CLL11
| . | CLL8 . | CLL10 . | CLL11 . | |||
|---|---|---|---|---|---|---|
| FC, n = 184 . | FCR, n = 209 . | BR, n = 158 . | FCR,* n = 179 . | R-Clb, n = 245 . | G-Clb, n = 229 . | |
| Patients | Previously untreated, physically fit | Previously untreated, physically fit; excluding patients with del(17p) | Previously untreated, with comorbidities | |||
| Median observation time, mo | 55 | 61 | 41 | |||
| PFS events, n (%) | 119 (65) | 107 (51) | 104 (66) | 87 (49) | 220 (90) | 163 (71) |
| PFS HR (95% CI) | 0.63 (0.48-0.82) | 0.63 (0.47-0.84) | 0.44 (0.36-0.54) | |||
| MRD negativity,† n (%) | 57 (31) | 143 (68) | 99 (63) | 128 (72) | 8 (3) | 82 (36) |
| MRD absolute difference, % | 37 | 9 | 33 | |||
| MRD relative risk‡ | 2.20 | 1.14 | 10.38 | |||
| . | CLL8 . | CLL10 . | CLL11 . | |||
|---|---|---|---|---|---|---|
| FC, n = 184 . | FCR, n = 209 . | BR, n = 158 . | FCR,* n = 179 . | R-Clb, n = 245 . | G-Clb, n = 229 . | |
| Patients | Previously untreated, physically fit | Previously untreated, physically fit; excluding patients with del(17p) | Previously untreated, with comorbidities | |||
| Median observation time, mo | 55 | 61 | 41 | |||
| PFS events, n (%) | 119 (65) | 107 (51) | 104 (66) | 87 (49) | 220 (90) | 163 (71) |
| PFS HR (95% CI) | 0.63 (0.48-0.82) | 0.63 (0.47-0.84) | 0.44 (0.36-0.54) | |||
| MRD negativity,† n (%) | 57 (31) | 143 (68) | 99 (63) | 128 (72) | 8 (3) | 82 (36) |
| MRD absolute difference, % | 37 | 9 | 33 | |||
| MRD relative risk‡ | 2.20 | 1.14 | 10.38 | |||
BR, bendamustine and rituximab; CI, confidence interval; FC, fludarabine and cyclophosphamide; FCR, fludarabine, cyclophosphamide, and rituximab; G-Clb, obinutuzumab plus chlorambucil; HR, hazard ratio; R-Clb, rituximab plus chlorambucil.
For the purpose of the model, FCR was considered the experimental arm (noninferiority trial).
PB at final response assessment within 75 to 195 (CLL8 and CLL10) or 56 to 190 (CLL11) days after the last day of treatment; if multiple values within this time window were available, the earliest dated result was used; patients with no MRD result but death/progressive disease shortly after last dose (within 90 [CLL8 and CLL10] or 56 [CLL11] days) are included as MRD+ (MRD-evaluable population).
Relative risk = MRD− rate on experimental arm/MRD− rate on control arm. A value of 0.5 was added to all counts of MRD responders and nonresponders to avoid division by zero.23 For all trials, PFS results are shown for the MRD-evaluable population. Data as of July 2010 (CLL8), May 2015 (CLL11), September 2016 (CLL10).