Selected key trials with comparative outcomes of TP53-mutated and non-TP53-mutated MCL
| Trial . | Regimen . | Outcome in TP53-mutated MCL . | Outcome in non-TP53-mutated MCL . |
|---|---|---|---|
| MCL2 and MCL32 | [1L] Induction: alternating R-CHOP / R-high-dose cytarabine → Consolidation: high-dose chemotherapy and ASCT | Median OS: 1.8 years∗ | Median OS: 12.7 years∗ |
| SHINE5 | [1L] placebo + BR | Median PFS: 11.0 months† | Median PFS: 52.9 months† |
| [1L] ibrutinib + BR | Median PFS: 28.8 months† | Median PFS: 80.6 months† | |
| TRIANGLE6 | [1L] R-CHOP/R-DHAP → ASCT → R maintenance vs Ibrutinib + R-CHOP/R-DHAP → ASCT → ibrutinib/R maintenance | FFS HR 0.14 favoring addition of ibrutinib to induction and maintenance†,‡ | FFS HR 0.57 favoring addition of ibrutinib to induction and maintenance†,‡ |
| AIM7 | [R/R] ibrutinib + venetoclax | Median PFS: 5 months∗ | Median PFS: ∼7 years∗ |
| SYMPATICO8 | [R/R] ibrutinib + placebo vs ibrutinib + venetoclax | PFS HR 0.57 favoring addition of venetoclax to ibrutinib† | PFS HR 0.52 favoring addition of venetoclax to ibrutinib† |
| BOVen1 | [1L] zanubrutinib + obinutuzumab + venetoclax | 2-year PFS: 72% | — |
| Trial . | Regimen . | Outcome in TP53-mutated MCL . | Outcome in non-TP53-mutated MCL . |
|---|---|---|---|
| MCL2 and MCL32 | [1L] Induction: alternating R-CHOP / R-high-dose cytarabine → Consolidation: high-dose chemotherapy and ASCT | Median OS: 1.8 years∗ | Median OS: 12.7 years∗ |
| SHINE5 | [1L] placebo + BR | Median PFS: 11.0 months† | Median PFS: 52.9 months† |
| [1L] ibrutinib + BR | Median PFS: 28.8 months† | Median PFS: 80.6 months† | |
| TRIANGLE6 | [1L] R-CHOP/R-DHAP → ASCT → R maintenance vs Ibrutinib + R-CHOP/R-DHAP → ASCT → ibrutinib/R maintenance | FFS HR 0.14 favoring addition of ibrutinib to induction and maintenance†,‡ | FFS HR 0.57 favoring addition of ibrutinib to induction and maintenance†,‡ |
| AIM7 | [R/R] ibrutinib + venetoclax | Median PFS: 5 months∗ | Median PFS: ∼7 years∗ |
| SYMPATICO8 | [R/R] ibrutinib + placebo vs ibrutinib + venetoclax | PFS HR 0.57 favoring addition of venetoclax to ibrutinib† | PFS HR 0.52 favoring addition of venetoclax to ibrutinib† |
| BOVen1 | [1L] zanubrutinib + obinutuzumab + venetoclax | 2-year PFS: 72% | — |
1L, frontline; ASCT, autologous stem cell transplantation; BR, bendamustine, rituximab; CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone; DHAP, dexamethasone, high-dose cytarabine, cisplatin or oxaliplatin; FFS, failure-free survival; HR, hazard ratio; MCL, mantle cell lymphoma, OS, overall survival; PFS, progression-free survival; R, rituximab; R/R, relapsed/refractory
Retrospective subgroup analyses of phase 2 trials
Prespecified subgroup analysis within phase 3 trial
Subgroup analysis based on p53 histopathological expression either categorized as low (≤50%) or high (>50%)