Summary table of U-MRD rates and outcomes of pivotal clinical trials in patients with treatment-naive and relapsed/refractory CLL
| Trial . | Phase . | Treatment setting . | Treatment . | MRD endpoint . | MRD detection method . | MRD detection level . | % U-MRD PB . | % U-MRD BM . | PFS/mPFS . | OS/mOS . |
|---|---|---|---|---|---|---|---|---|---|---|
| CLL823 | 3 | TN | FC FCR | Secondary | Flow cytometry ASO-PCR | 10−4 | 35% 63% | 28% 44% | 32.9 mo 56.8 mo | 86 mo NR |
| NIH24 | 2 | TN/RR | I | Exploratory | Flow cytometry | 10−4 | 10.2% | 8% | 5-year: TP53 cohort: 58.2% Elderly cohort: 81.2% | 5-year: TP53 cohort: 75.7% Elderly cohort: 83.85% |
| E191221 | 3 | TN | IR FCR | Exploratory | Flow cytometry | 10−4 | 7.9% 30.3% | NA | 5-year: 78% 51% | mOS: NR NR |
| ELEVATE-TN25 | 3 | TN | A AO CO | Exploratory | Flow cytometry | 10−4 | 7% 49% 61% | 0% 61% 10.9% | 48 mo: 77.9% 87% 25.1% | mOS: NR NR NR |
| CLL147 | 3 | TN | VO CO | Secondary | ASO-PCR | 10−4-10−6 | 39.6 mo: 81% 49.5% | 17.1% 56.9% | 5-year: 62.6% 27% | 5-year: 87% 87% |
| FLAIR27 * | 3 | TN | FCR IR | Secondary | Flow cytometry | 10−4 | 75% 10% | 46% 4% | mPFS: 67 mo NR | mOS: NR NR |
| CAPTIVATE: MRD28 * | 2 | TN | IV + Placebo IV + I | Secondary | Flow cytometry | 10−4 | 75% | 68% | 4-year: 88% 95% | 4-year: 100% 98% |
| CAPTIVATE: Fixed Duration29,30 | 2 | TN | IV | Secondary | Flow cytometry | 10−4 | 77% | 60% | 95% at 24 mo | 98% at 24 mo |
| GLOW32 | 3 | TN | IV CO | Secondary | NGS | 10−4, 10−5 | 43.4% 18.6% | 40.6% 7.6% | 30 mo: 86.7% 35.5% | mOS: NR NR |
| MDACC31 | 2 | TN | IV | Secondary | Flow cytometry | 10−4 | NA | 75% | 3-year: 93% | 3-year: 96% |
| CLL1333 | 3 | TN | FCR/BR VR VO VIO | Primary | Flow cytometry | 10−4 | 52% 57% 86.5% 92.2% | 37.1% 43% 72.5% 77.9% | 3 year: 75.5% 80.8% 87/.7% 90.5% | 3-year: 95% 96.5% 96.3% 95.3% |
| MURANO34 | 3 | RR | BR VR | Secondary | ASO-PCR Flow cytometry | 10−4 | 13.3% 62.4% | 1.5% 27.3% | mPFS: 17 mo 53.6 mo | 60 mo: 62.2% 82.1% |
| CLARITY35 * | 2 | RR | IV | Primary | Flow cytometry | 10−4 | 53% | 36% | NR | 100% |
| CLL3X36 | 2 | RR | Allogeneic HSCT | Secondary | Flow cytometry ASO-PCR | 10−4 | 10-year: 34% | 10-year: 51% | ||
| TRANSCEND-004 CLL41 | 1-2 | RR | Lisocabtagene maraleucel | Secondary | NGS | 10−4 | 63% | 59% | 17.97 mo | 43.17 mo |
| Trial . | Phase . | Treatment setting . | Treatment . | MRD endpoint . | MRD detection method . | MRD detection level . | % U-MRD PB . | % U-MRD BM . | PFS/mPFS . | OS/mOS . |
|---|---|---|---|---|---|---|---|---|---|---|
| CLL823 | 3 | TN | FC FCR | Secondary | Flow cytometry ASO-PCR | 10−4 | 35% 63% | 28% 44% | 32.9 mo 56.8 mo | 86 mo NR |
| NIH24 | 2 | TN/RR | I | Exploratory | Flow cytometry | 10−4 | 10.2% | 8% | 5-year: TP53 cohort: 58.2% Elderly cohort: 81.2% | 5-year: TP53 cohort: 75.7% Elderly cohort: 83.85% |
| E191221 | 3 | TN | IR FCR | Exploratory | Flow cytometry | 10−4 | 7.9% 30.3% | NA | 5-year: 78% 51% | mOS: NR NR |
| ELEVATE-TN25 | 3 | TN | A AO CO | Exploratory | Flow cytometry | 10−4 | 7% 49% 61% | 0% 61% 10.9% | 48 mo: 77.9% 87% 25.1% | mOS: NR NR NR |
| CLL147 | 3 | TN | VO CO | Secondary | ASO-PCR | 10−4-10−6 | 39.6 mo: 81% 49.5% | 17.1% 56.9% | 5-year: 62.6% 27% | 5-year: 87% 87% |
| FLAIR27 * | 3 | TN | FCR IR | Secondary | Flow cytometry | 10−4 | 75% 10% | 46% 4% | mPFS: 67 mo NR | mOS: NR NR |
| CAPTIVATE: MRD28 * | 2 | TN | IV + Placebo IV + I | Secondary | Flow cytometry | 10−4 | 75% | 68% | 4-year: 88% 95% | 4-year: 100% 98% |
| CAPTIVATE: Fixed Duration29,30 | 2 | TN | IV | Secondary | Flow cytometry | 10−4 | 77% | 60% | 95% at 24 mo | 98% at 24 mo |
| GLOW32 | 3 | TN | IV CO | Secondary | NGS | 10−4, 10−5 | 43.4% 18.6% | 40.6% 7.6% | 30 mo: 86.7% 35.5% | mOS: NR NR |
| MDACC31 | 2 | TN | IV | Secondary | Flow cytometry | 10−4 | NA | 75% | 3-year: 93% | 3-year: 96% |
| CLL1333 | 3 | TN | FCR/BR VR VO VIO | Primary | Flow cytometry | 10−4 | 52% 57% 86.5% 92.2% | 37.1% 43% 72.5% 77.9% | 3 year: 75.5% 80.8% 87/.7% 90.5% | 3-year: 95% 96.5% 96.3% 95.3% |
| MURANO34 | 3 | RR | BR VR | Secondary | ASO-PCR Flow cytometry | 10−4 | 13.3% 62.4% | 1.5% 27.3% | mPFS: 17 mo 53.6 mo | 60 mo: 62.2% 82.1% |
| CLARITY35 * | 2 | RR | IV | Primary | Flow cytometry | 10−4 | 53% | 36% | NR | 100% |
| CLL3X36 | 2 | RR | Allogeneic HSCT | Secondary | Flow cytometry ASO-PCR | 10−4 | 10-year: 34% | 10-year: 51% | ||
| TRANSCEND-004 CLL41 | 1-2 | RR | Lisocabtagene maraleucel | Secondary | NGS | 10−4 | 63% | 59% | 17.97 mo | 43.17 mo |
Indicates a trial that used MRD to guide treatment decisions.
A, acalabrutinib; AO, acalabrutinib-obinutuzumab; ASO-PCR, allele-specific oligonucleotide polymerase chain reaction; BM, bone marrow; BR, bendamustine-rituximab; CO, chlorambucil-obintuzumab; FC, fludarabine-cyclophosphamide; FCR, fludarabine-cyclophosphamide-rituximab; HSCT, hematopoietic stem cell transplant; I, ibrutinib; IV, ibrutinib-venetoclax; IR, ibrutinib-rituximab; mOS, median OS; mPFS, median PFS; MRD, measurable residual disease; NA, not available; NGS, next-generation sequencing NR, not reached; OS, verall survival; PFS, progression-free survival; PB, peripheral blood; RR, relapsed/refractory; TN, treatment-naive; U-MRD, undetectable-MRD; VR, venetoclax-rituximab.