Efficacy of selected first-line regimens in CLL
| Reference . | Phase . | Treatment . | Patient populationa . | Median FU . | PFS . | Comment . |
|---|---|---|---|---|---|---|
| Ibrutinib . | ||||||
| ECOG E19128 | 3 | IR FCR | Age ≤70 y | 70 mo | 78% at 5 y 51% at 5 y | Excluded del17p OS benefit with IR (HR, 0.47) |
| NCRI FLAIR7 | 3 | IR FCR | Age ≤75 y | 53 mo | Median NR Median 67 mo | Excluded del17p >20% of cells No OS benefit with IR |
| Alliance A04170214 | 3 | I IR BR | Age ≥65 y | 55 mo | 76% at 4 y 76% at 4 y 47% at 4 y | No PFS difference between 2 IBR arms |
| iLLUMINATE42 | 3 | IO Chl-O | Age ≥65 y or with comorbidities | 45 mo | 74% at 42 mo 33% at 42 mo | 16% with TP53 aberration |
| RESONATE-243 | 3 | I Chl | Age ≥65 y | 89 mo | 59% at 7 y 9% at 7 y | Excluded del17p OS benefit with I (HR, 0.45) |
| MDACC phase 221 | 2 | I IR | RR or TN CLL | 36 mo | 86% at 3 y 87% at 3 y | Mixed with TN (13%) and RR (87%) CLL 27% with TP53 aberration |
| NIH phase 217 | 2 | I | TP53 aberration | 78 mo | 61% at 6 y | All 34 TN patients with TP53 aberration |
| Acalabrutinib or zanubrutinib | ||||||
| ELEVATE-TN20 | 3 | A AO Chl-O | Age ≥65 y or with comorbidities | 58 mo | 72% at 5 y 84% at 5 y 21% at 5 y | 14% with TP53 aberration |
| SEQUOIA Arm A/B44 | 3 | Z BR | Age ≥65 y or with comorbidities | 26 mo | 86% at 2 y 70% at 2 y | Excluded del17p 6% with TP53 mutation |
| SEQUOIA Arm C19 | 3b | Z | TP53 aberration Age ≥65 y or with comorbidities | 15 mo | 89% at 18 mo | All 109 TN patients with del17p |
| Venetoclax | ||||||
| CLL1416 | 3 | VO Chl-O | CIRS score >6 | 52 mo | 74% at 4 y 35% at 4 y | 7% with TP53 aberration PFS benefit (HR 0.33) with VO, no OS benefit |
| CLL1312 | 3 | FCR/BR VR VO IVO | Fit, CIRS score ≤6 | 39 mo | 76% at 3 y 81% at 3 y 88% at 3 y 91% at 3 y | Excluded TP53 aberration PFS benefit and higher rates of uMRD in VO-containing regimens compared with VR or CIT |
| Reference . | Phase . | Treatment . | Patient populationa . | Median FU . | PFS . | Comment . |
|---|---|---|---|---|---|---|
| Ibrutinib . | ||||||
| ECOG E19128 | 3 | IR FCR | Age ≤70 y | 70 mo | 78% at 5 y 51% at 5 y | Excluded del17p OS benefit with IR (HR, 0.47) |
| NCRI FLAIR7 | 3 | IR FCR | Age ≤75 y | 53 mo | Median NR Median 67 mo | Excluded del17p >20% of cells No OS benefit with IR |
| Alliance A04170214 | 3 | I IR BR | Age ≥65 y | 55 mo | 76% at 4 y 76% at 4 y 47% at 4 y | No PFS difference between 2 IBR arms |
| iLLUMINATE42 | 3 | IO Chl-O | Age ≥65 y or with comorbidities | 45 mo | 74% at 42 mo 33% at 42 mo | 16% with TP53 aberration |
| RESONATE-243 | 3 | I Chl | Age ≥65 y | 89 mo | 59% at 7 y 9% at 7 y | Excluded del17p OS benefit with I (HR, 0.45) |
| MDACC phase 221 | 2 | I IR | RR or TN CLL | 36 mo | 86% at 3 y 87% at 3 y | Mixed with TN (13%) and RR (87%) CLL 27% with TP53 aberration |
| NIH phase 217 | 2 | I | TP53 aberration | 78 mo | 61% at 6 y | All 34 TN patients with TP53 aberration |
| Acalabrutinib or zanubrutinib | ||||||
| ELEVATE-TN20 | 3 | A AO Chl-O | Age ≥65 y or with comorbidities | 58 mo | 72% at 5 y 84% at 5 y 21% at 5 y | 14% with TP53 aberration |
| SEQUOIA Arm A/B44 | 3 | Z BR | Age ≥65 y or with comorbidities | 26 mo | 86% at 2 y 70% at 2 y | Excluded del17p 6% with TP53 mutation |
| SEQUOIA Arm C19 | 3b | Z | TP53 aberration Age ≥65 y or with comorbidities | 15 mo | 89% at 18 mo | All 109 TN patients with del17p |
| Venetoclax | ||||||
| CLL1416 | 3 | VO Chl-O | CIRS score >6 | 52 mo | 74% at 4 y 35% at 4 y | 7% with TP53 aberration PFS benefit (HR 0.33) with VO, no OS benefit |
| CLL1312 | 3 | FCR/BR VR VO IVO | Fit, CIRS score ≤6 | 39 mo | 76% at 3 y 81% at 3 y 88% at 3 y 91% at 3 y | Excluded TP53 aberration PFS benefit and higher rates of uMRD in VO-containing regimens compared with VR or CIT |
Bold indicates treatment arms containing targeted agents.
A, acalabrutinib; BR, bendamustine and rituximab; Chl, chlorambucil; CIRS, cumulative illness rating scale; del17p, deletion 17p; FU, follow-up; HR, hazard ratio; I, ibrutinib; O, obinutuzumab; NR, not reached; R, rituximab; RR, relapsed or refractory; V, venetoclax; y, years; Z, zanubrutinib.
All TN CLL unless otherwise specified.
Nonrandomized arm of a phase 3 study.