Selected frontline trials in MCL incorporating novel agents and CIT with outcomes of high-risk patients highlighted
| Trial . | Treatment(s) . | High-risk patients . | Outcomes . | |
|---|---|---|---|---|
| Overall . | High-risk patients . | |||
| SHINE23 (phase 3, n = 523) | BR and RM with ibrutinib or placebo | High s-MIPI = 34% Blastoid = 9% TP53 mutated = 10% | PFS 81 months (BR + ibrutinib) vs 53 mo (BR) | No benefit from ibrutinib in high-risk s-MIPI (HR, 1.02; 95% CI, 0.7-1.5) or mutated TP53 (mPFS, 29 mo vs 11 mo; HR, 0.95; 95% CI, 0.5-1.8). For blastoid: median PFS 26 mo (95% CI, 6-84) with ibrutinib vs 10 mo (95% CI, 6-44 mo) with placebo. |
| ECHO24 (phase 3, n = 598) | BR and RM with acalabrutinib or placebo | High s-MIPI = 24% Ki-67 ≥ 30% = 48% Blastoid = 13% TP53 mutated = 9% | PFS 66 mo (BR + acalabrutinib) vs 50 mo (BR) | Not reported |
| TRIANGLE25 (phase 3, n = 870) | 3 arms (A, I, A + I) (A) R-CHOP/R-DHAP(X) → ASCT (I) Ibrutinib + R-CHOP/ R-DHAP(X) → ibrutinib maintenance (A+I) Ibrutinib + R-CHOP/ R-DHAP(X) → ASCT → ibrutinib maintenance | High MIPI = 15% Ki-67 ≥ 30% = 32% Blastoid = 12% p53 > 50% = 14% High-risk biology = 20% | 3-y FFS: A + I, 88% I, 86% A, 72% 3-y OS: A + I, 91% I, 92% A, 86% | A ± I vs A: High MIPI: HR = 0.58 (98.3% CI, 0-1.32) Blastoid: HR, 0.59 (0-1.63) Ki-67 ≥ 30%: HR, 0.43 (0-0.83) p53 expression >50%: HR, 0.14 (0-0.57) High-risk biology: HR, 0.31 (0-0.78) A vs I: High MIPI: HR, 1.86 (98.3% CI, 0-4.25) Blastoid: HR, 1.01 (0-2.52) Ki-67 ≥ 30%: HR, 2.5 (0-4.78) p53 expression >50%: HR, 3.24 (0-8.5) High-risk biology: HR, 2.24 (0-4.85) |
| WINDOW-126 (phase 2, n = 131) | Ibrutinib + rituximab → HCVAD/MA x4-8 cycles | High MIPI = 8% High MIPI-b = 36% Blastoid = 12% Ki-67 ≥ 30% = 45% TP53 aberrations 32% | 3-y PFS 79% 3-y OS 95% | CR rate: TP53-mutated 55% vs 91% PFS: Ki-67 ≥ 30% (HR, 2.73; P = .017) Low/intermediate MIPI-b (HR. 0.17 and 0.24; P = .004) Classic vs blastoid (HR, 0.24; P < .001) TP53 aberrations (HR, 3.87; P = .069) |
| WINDOW-227 (phase 2, n = 50) | Ibrutinib, rituximab, venetoclax → HCVAD/MA × 0-4 cycles | High s-MIPI = 6% Blastoid = 12% TP53 aberrations = 25% Ki-67 ≥ 30% = 41% | 3-y PFS 86% 3-y OS 86% | PFS and OS not significantly different based on s-MIPI and TP53 status PFS and OS inferior in Ki-67 ≥ 50% and blastoid |
| WAMM33 (phase 2, n = 444) | Rituximab + acalabrutinib → R-DHAX → ASCT | Ki-67 > 30% = 66% Blastoid = 9% | 2-y PFS 73% 2-y OS 79% | Not reported |
| VR-BAC28 (phase 2, n = 54) | R-BAC + venetoclax | Ki-67 ≥ 30% = 63% Blastoid = 24% TP53 aberrations = 63% | 2-y PFS 58% 2-y OS 66% | Blastoid morphology and TP53 mutations were associated with inferior outcomes in multivariate analysis. |
| Trial . | Treatment(s) . | High-risk patients . | Outcomes . | |
|---|---|---|---|---|
| Overall . | High-risk patients . | |||
| SHINE23 (phase 3, n = 523) | BR and RM with ibrutinib or placebo | High s-MIPI = 34% Blastoid = 9% TP53 mutated = 10% | PFS 81 months (BR + ibrutinib) vs 53 mo (BR) | No benefit from ibrutinib in high-risk s-MIPI (HR, 1.02; 95% CI, 0.7-1.5) or mutated TP53 (mPFS, 29 mo vs 11 mo; HR, 0.95; 95% CI, 0.5-1.8). For blastoid: median PFS 26 mo (95% CI, 6-84) with ibrutinib vs 10 mo (95% CI, 6-44 mo) with placebo. |
| ECHO24 (phase 3, n = 598) | BR and RM with acalabrutinib or placebo | High s-MIPI = 24% Ki-67 ≥ 30% = 48% Blastoid = 13% TP53 mutated = 9% | PFS 66 mo (BR + acalabrutinib) vs 50 mo (BR) | Not reported |
| TRIANGLE25 (phase 3, n = 870) | 3 arms (A, I, A + I) (A) R-CHOP/R-DHAP(X) → ASCT (I) Ibrutinib + R-CHOP/ R-DHAP(X) → ibrutinib maintenance (A+I) Ibrutinib + R-CHOP/ R-DHAP(X) → ASCT → ibrutinib maintenance | High MIPI = 15% Ki-67 ≥ 30% = 32% Blastoid = 12% p53 > 50% = 14% High-risk biology = 20% | 3-y FFS: A + I, 88% I, 86% A, 72% 3-y OS: A + I, 91% I, 92% A, 86% | A ± I vs A: High MIPI: HR = 0.58 (98.3% CI, 0-1.32) Blastoid: HR, 0.59 (0-1.63) Ki-67 ≥ 30%: HR, 0.43 (0-0.83) p53 expression >50%: HR, 0.14 (0-0.57) High-risk biology: HR, 0.31 (0-0.78) A vs I: High MIPI: HR, 1.86 (98.3% CI, 0-4.25) Blastoid: HR, 1.01 (0-2.52) Ki-67 ≥ 30%: HR, 2.5 (0-4.78) p53 expression >50%: HR, 3.24 (0-8.5) High-risk biology: HR, 2.24 (0-4.85) |
| WINDOW-126 (phase 2, n = 131) | Ibrutinib + rituximab → HCVAD/MA x4-8 cycles | High MIPI = 8% High MIPI-b = 36% Blastoid = 12% Ki-67 ≥ 30% = 45% TP53 aberrations 32% | 3-y PFS 79% 3-y OS 95% | CR rate: TP53-mutated 55% vs 91% PFS: Ki-67 ≥ 30% (HR, 2.73; P = .017) Low/intermediate MIPI-b (HR. 0.17 and 0.24; P = .004) Classic vs blastoid (HR, 0.24; P < .001) TP53 aberrations (HR, 3.87; P = .069) |
| WINDOW-227 (phase 2, n = 50) | Ibrutinib, rituximab, venetoclax → HCVAD/MA × 0-4 cycles | High s-MIPI = 6% Blastoid = 12% TP53 aberrations = 25% Ki-67 ≥ 30% = 41% | 3-y PFS 86% 3-y OS 86% | PFS and OS not significantly different based on s-MIPI and TP53 status PFS and OS inferior in Ki-67 ≥ 50% and blastoid |
| WAMM33 (phase 2, n = 444) | Rituximab + acalabrutinib → R-DHAX → ASCT | Ki-67 > 30% = 66% Blastoid = 9% | 2-y PFS 73% 2-y OS 79% | Not reported |
| VR-BAC28 (phase 2, n = 54) | R-BAC + venetoclax | Ki-67 ≥ 30% = 63% Blastoid = 24% TP53 aberrations = 63% | 2-y PFS 58% 2-y OS 66% | Blastoid morphology and TP53 mutations were associated with inferior outcomes in multivariate analysis. |
HR, hazard ratio.