Comparison of published studies in which clonal relatedness of the underlying CLL and subsequent RT-DLBCL has been examined and where there has been reporting in the study of clinical outcomes as per clonal relatedness
| Author name, year . | Type of study . | Therapy delivered . | Total number of patients in the study . | Number of patients where clonality results available (% clonally related) . | Method of clonality assessment . | Type of outcome assessment . | Outcome assessment . | CASP score—risk of bias . |
|---|---|---|---|---|---|---|---|---|
| Nakamura et al,14 2000 | Observational study at time of diagnosis | Not specified | 3 | 2 (0.0%) | Immunoglobulin gene rearrangement | Descriptive only—no statistical analysis | N/A | High |
| Mao et al,15 2007 | Observational study at time of diagnosis | Not specified | 34 | 23 (78.3%) | Immunoglobulin gene rearrangement | Outcome measure not specified but outcomes examined by Cox’s proportional hazards regression model | No survival difference between groups demonstrated | Moderate |
| Rossi et al,10 2011 | Observational study | (R)CHOP, 65% Fludarabine-based, 8.5% Other, 26.5% | 86 | 63 (79.4%) | Immunoglobulin gene rearrangement | Median OS | Significant improvement in clonally unrelated vs clonally related | Low |
| Eyre et al,16 2016 | Interventional study in first-line patients | CHOP + ofatumumab | 37 | 17 (94.1%) | Immunoglobulin gene rearrangement | Descriptive only—no statistical analysis | N/A | High |
| Innocenti et al,17 2018 | Observational study at time of diagnosis in patients with ibrutinib-treated CLL | RCHOP | 2 | 2 (100%) | Immunoglobulin gene rearrangement | Descriptive only—no statistical analysis | N/A | High |
| Rogers et al,18 2019 | Observational study in R/R patients | PD-1 inhibitors | 10 | 2 (100%) | Not described | Descriptive only—no statistical analysis | N/A | High |
| Abrisqueta et al,19 2020 | Observational study at time of diagnosis | (R)CHOP, 60% Other, 18% None, 22% | 112 | 35 (85.7%) | Immunoglobulin gene rearrangement | Median OS | Significant improvement in clonally unrelated vs clonally related | Moderate |
| Wang et al,9 2020 | Observational study at time of diagnosis | RCHOP, 65% Targeted therapies, 11% Other, 19% None, 5% | 204 | 21 (57.1%) | Immunoglobulin gene rearrangement | Median OS | No significant difference in median OS demonstrated between groups | Moderate |
| Kittai et al,20 2020 | Observational study in R/R patients | Axicabtagene ciloleucel | 9 | 5 (100%) | Immunoglobulin gene rearrangement | Descriptive only—no statistical analysis | N/A | High |
| Hess et al,21 2022 | Observational study at time of diagnosis | RCHOP-like | 24 | 7 (85.7%) | Chromosomal microarray analysis | Descriptive only—no statistical analysis | N/A | High |
| Gángó et al,22 2022 | Observational study at time of diagnosis in ibrutinib or patients with venetoclax-treated CLL | Not specified | 6 | 4 (75%) | Immunoglobulin gene rearrangement | Descriptive only—no statistical analysis | N/A | High |
| Broséus et al,23 2023 | Observational study at time of diagnosis | RCHOP-like, 87% Platinum based, 7% | 58 | 58 (75.9%) | Genome-wide methylation and whole-transcriptome profiling | Median OS | Significant improvement in clonally unrelated vs clonally related (assessed in 37.9% of entire cohort) | Low |
| Parry et al,7 2023 | Observational study of patients at time of diagnosis and R/R patients | R chemotherapy, 77% Allogeneic, HSCT 8% Autologous HSCT, 7% CAR-T, 3% | 52 | 52 (86.5%) | Whole exome and whole genome sequencing | Median OS | Significant improvement in clonally unrelated vs clonally related | Moderate |
| Wierda et al,24 2024 | Interventional study in first line and R/R patients | Pirtobrutinib | 82 | 21 (85.7%) | Immunoglobulin gene rearrangement | ORR in patients treated with pirtobrutinib—no statistical analysis | Similar between groups (66.67% in clonally unrelated, 61.1% in clonally related) | Moderate |
| Tedeschi et al,25 2024 | Interventional study of patients treated in the first line | Atezolizumab, venetoclax, and obinutuzumab | 28 | 24 (83.3%) | Immunoglobulin gene rearrangement | ORR | No significant difference between groups demonstrated | Moderate |
| Author name, year . | Type of study . | Therapy delivered . | Total number of patients in the study . | Number of patients where clonality results available (% clonally related) . | Method of clonality assessment . | Type of outcome assessment . | Outcome assessment . | CASP score—risk of bias . |
|---|---|---|---|---|---|---|---|---|
| Nakamura et al,14 2000 | Observational study at time of diagnosis | Not specified | 3 | 2 (0.0%) | Immunoglobulin gene rearrangement | Descriptive only—no statistical analysis | N/A | High |
| Mao et al,15 2007 | Observational study at time of diagnosis | Not specified | 34 | 23 (78.3%) | Immunoglobulin gene rearrangement | Outcome measure not specified but outcomes examined by Cox’s proportional hazards regression model | No survival difference between groups demonstrated | Moderate |
| Rossi et al,10 2011 | Observational study | (R)CHOP, 65% Fludarabine-based, 8.5% Other, 26.5% | 86 | 63 (79.4%) | Immunoglobulin gene rearrangement | Median OS | Significant improvement in clonally unrelated vs clonally related | Low |
| Eyre et al,16 2016 | Interventional study in first-line patients | CHOP + ofatumumab | 37 | 17 (94.1%) | Immunoglobulin gene rearrangement | Descriptive only—no statistical analysis | N/A | High |
| Innocenti et al,17 2018 | Observational study at time of diagnosis in patients with ibrutinib-treated CLL | RCHOP | 2 | 2 (100%) | Immunoglobulin gene rearrangement | Descriptive only—no statistical analysis | N/A | High |
| Rogers et al,18 2019 | Observational study in R/R patients | PD-1 inhibitors | 10 | 2 (100%) | Not described | Descriptive only—no statistical analysis | N/A | High |
| Abrisqueta et al,19 2020 | Observational study at time of diagnosis | (R)CHOP, 60% Other, 18% None, 22% | 112 | 35 (85.7%) | Immunoglobulin gene rearrangement | Median OS | Significant improvement in clonally unrelated vs clonally related | Moderate |
| Wang et al,9 2020 | Observational study at time of diagnosis | RCHOP, 65% Targeted therapies, 11% Other, 19% None, 5% | 204 | 21 (57.1%) | Immunoglobulin gene rearrangement | Median OS | No significant difference in median OS demonstrated between groups | Moderate |
| Kittai et al,20 2020 | Observational study in R/R patients | Axicabtagene ciloleucel | 9 | 5 (100%) | Immunoglobulin gene rearrangement | Descriptive only—no statistical analysis | N/A | High |
| Hess et al,21 2022 | Observational study at time of diagnosis | RCHOP-like | 24 | 7 (85.7%) | Chromosomal microarray analysis | Descriptive only—no statistical analysis | N/A | High |
| Gángó et al,22 2022 | Observational study at time of diagnosis in ibrutinib or patients with venetoclax-treated CLL | Not specified | 6 | 4 (75%) | Immunoglobulin gene rearrangement | Descriptive only—no statistical analysis | N/A | High |
| Broséus et al,23 2023 | Observational study at time of diagnosis | RCHOP-like, 87% Platinum based, 7% | 58 | 58 (75.9%) | Genome-wide methylation and whole-transcriptome profiling | Median OS | Significant improvement in clonally unrelated vs clonally related (assessed in 37.9% of entire cohort) | Low |
| Parry et al,7 2023 | Observational study of patients at time of diagnosis and R/R patients | R chemotherapy, 77% Allogeneic, HSCT 8% Autologous HSCT, 7% CAR-T, 3% | 52 | 52 (86.5%) | Whole exome and whole genome sequencing | Median OS | Significant improvement in clonally unrelated vs clonally related | Moderate |
| Wierda et al,24 2024 | Interventional study in first line and R/R patients | Pirtobrutinib | 82 | 21 (85.7%) | Immunoglobulin gene rearrangement | ORR in patients treated with pirtobrutinib—no statistical analysis | Similar between groups (66.67% in clonally unrelated, 61.1% in clonally related) | Moderate |
| Tedeschi et al,25 2024 | Interventional study of patients treated in the first line | Atezolizumab, venetoclax, and obinutuzumab | 28 | 24 (83.3%) | Immunoglobulin gene rearrangement | ORR | No significant difference between groups demonstrated | Moderate |
CAR-T, chimeric antigen receptor therapy; CASP, Critical Appraisal Skills Programme; HSCT, hematopoietic stem cell transplant; N/A, not available; ORR, overall response rate; PD-1, programmed death-1; RCHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone; (R)CHOP: (rituximab), cyclophosphamide, doxorubicin, vincristine, and prednisolone.