Selected frontline CIT trials in MCL with outcomes of high-risk patients highlighted
| Trial (n) . | Treatment(s) . | High-risk patients . | Outcomes . | |
|---|---|---|---|---|
| Overall population . | High-risk patients . | |||
| European MCL Younger (n = 466)48 | R-CHOP/R-DHAP → ASCT vs R-CHOP → ASCT | High MIPI = 14% High MIPI-c = 5% Ki-67 ≥ 30% = 27% Blastoid = 9% p53 > 50% = 12% | R-CHOP/R-DHAP: mTTF = 8 y; mOS = NR R-CHOP: mTTF = 4 y; mOS = 11 y | Benefit in TTF from HDAC was similar across MIPI and MIPI-c risk groups, Ki-67, morphology, and “tended” to be stronger in p53 overexpression |
| LYMA (n = 240)49,50 | R-DHAP/ASCT followed by rituximab vs observation | High MIPI = 18% Ki-67 > 30% = 35% Blastoid = 10% | Rituximab: mEFS = NR, 7-y OS = 83% Observation: mEFS = 6 y, 7-y OS = 72% | High MIPI: mPFS and OS = 3.9 and 4.7 y |
| Retrospective/phase 2 (n = 88)51 | BR/R-HDAC | High MIPI = 19% Ki-67 > 30% = 24% Blastoid/pleomorphic = 12% | 3-y PFS = 83% 3-y OS = 92% | High MIPI 3-y PFS 76% Blastoid/pleomorphic 3-y PFS 66% No association between PFS and Ki-67 > 30% |
| Single-center phase 2 (n = 97)52 | R-HCVAD | Ki-67 ≥ 30% = 8% Blastoid/pleomorphic = 15% | MIPI predicted OS in overall and older patient cohorts Blastoid not associated with EFS or OS | |
| Nordic MCL2 and MCL3 trials (n = 321, MCL2 = 159, MCL3 = 162)6,53,54 | R-maxi-CHOP + R-HDAC | High MIPI = 22% Ki-67 ≥ 30% = 42% Blastoid = 18% | mPFS = 8 y mOS = 12.5 y | High MIPI: mPFS and mOS = 2.5 and 4 y MIPI but not blastoid morphology associated PFS and OS in MVA TP53 mutation: median PFS and OS = 0.9 and 1.8 y Del17 (without TP53 mutation): PFS = 3.1 y and OS = 8 y |
| Phase 2 (n = 57)55 | R-BAC | High MIPI = 44% Ki-67 ≥ 30% = 31% Blastoid/pleomorphic = 25% | 7-y PFS = 55% 7-y OS = 63% | Morphology strongest factor for PFS in MVA |
| Trial (n) . | Treatment(s) . | High-risk patients . | Outcomes . | |
|---|---|---|---|---|
| Overall population . | High-risk patients . | |||
| European MCL Younger (n = 466)48 | R-CHOP/R-DHAP → ASCT vs R-CHOP → ASCT | High MIPI = 14% High MIPI-c = 5% Ki-67 ≥ 30% = 27% Blastoid = 9% p53 > 50% = 12% | R-CHOP/R-DHAP: mTTF = 8 y; mOS = NR R-CHOP: mTTF = 4 y; mOS = 11 y | Benefit in TTF from HDAC was similar across MIPI and MIPI-c risk groups, Ki-67, morphology, and “tended” to be stronger in p53 overexpression |
| LYMA (n = 240)49,50 | R-DHAP/ASCT followed by rituximab vs observation | High MIPI = 18% Ki-67 > 30% = 35% Blastoid = 10% | Rituximab: mEFS = NR, 7-y OS = 83% Observation: mEFS = 6 y, 7-y OS = 72% | High MIPI: mPFS and OS = 3.9 and 4.7 y |
| Retrospective/phase 2 (n = 88)51 | BR/R-HDAC | High MIPI = 19% Ki-67 > 30% = 24% Blastoid/pleomorphic = 12% | 3-y PFS = 83% 3-y OS = 92% | High MIPI 3-y PFS 76% Blastoid/pleomorphic 3-y PFS 66% No association between PFS and Ki-67 > 30% |
| Single-center phase 2 (n = 97)52 | R-HCVAD | Ki-67 ≥ 30% = 8% Blastoid/pleomorphic = 15% | MIPI predicted OS in overall and older patient cohorts Blastoid not associated with EFS or OS | |
| Nordic MCL2 and MCL3 trials (n = 321, MCL2 = 159, MCL3 = 162)6,53,54 | R-maxi-CHOP + R-HDAC | High MIPI = 22% Ki-67 ≥ 30% = 42% Blastoid = 18% | mPFS = 8 y mOS = 12.5 y | High MIPI: mPFS and mOS = 2.5 and 4 y MIPI but not blastoid morphology associated PFS and OS in MVA TP53 mutation: median PFS and OS = 0.9 and 1.8 y Del17 (without TP53 mutation): PFS = 3.1 y and OS = 8 y |
| Phase 2 (n = 57)55 | R-BAC | High MIPI = 44% Ki-67 ≥ 30% = 31% Blastoid/pleomorphic = 25% | 7-y PFS = 55% 7-y OS = 63% | Morphology strongest factor for PFS in MVA |
MIPI-c, Combined MIPI; mEFS, median event-free survival; mOS, median OS; mPFS, median PFS; mTTF, median time to treatment failure; MVA, multivariate analysis; NR, not reached.