Selected frontline trials of novel agents in MCL with outcomes of high-risk patients highlighted
| Trial . | Treatment(s) . | High-risk patients . | Outcomes . | |
|---|---|---|---|---|
| Overall . | High-risk patients . | |||
| IMCL-201529 (phase 2, n = 50) | Ibrutinib + rituximab | Blastoid and Ki-67 ≥ 30% excluded High MIPI = 38% TP53 mutations = 15% | 3-y PFS 93% 3-y OS 92% | High MIPI and TP53 aberrations associated with inferior PFS and OS. In TP53 mutated, mPFS of 39 mo vs not reached in wild type. |
| NCT0188056730 (phase 2, n = 50) | Ibrutinib + rituximab | Blastoid and Ki-67 ≥ 50% excluded High s-MIPI = 16% High MIPI-b = 28% TP53 aberrations = 17% | 3-y PFS 87% 3-y OS 94% | Ki-67 30-50% associated with lower ORR/CR rate. High s-MIPI associated with inferior PFS. TP53 aberrations associated with inferior OS but not PFS. |
| NCT0521418331 (phase 2, n = 50) | Acalabrutinib + rituximab | High s-MIPI = 22% Blastoid = 8% TP53 aberrations = 28% (23% with mutations) | 2-y PFS 92% 2-y OS 96% | Not reported |
| OAsIs I35,36 (phase 1/2, n = 15, treatment-naive cohort) | Ibrutinib, obinutuzumab, and venetoclax | High MIPI = 27% High MIPI-b = 55% TP53 mutation = 13% del17p deletion = 40% | 4-y PFS 80% 4-y OS 93% | Not reported |
| ACE-LY-10638 (phase 1b, n = 21) | Acalabrutinib, rituximab, and venetoclax | High s-MIPI = 19% Blastoid = 5% Ki-67 ≥ 30% = 48% | 2-y PFS 54% (95% when censored for COVID-19 deaths) 2-y OS 74% | Not reported |
| BOVen39 (phase 2, n = 25) | Zanubrutinib, obinutuzumab, and venetoclax | High MIPI = 68% Ki-67 ≥ 30% = 67% Blastoid = 20% TP53 mutated = 100% Del17p = 48% | 2-year PFS 72% 2-y PFS 75% | No significant association between disease-free survival and baseline factors, including Ki-67, morphology, and biallelic TP53 inactivation |
| NCT0386318443 (phase 2, n = 24) | Acalabrutinib, lenalidomide, and rituximab | High MIPI = 21% Ki-67 ≥ 30% = 29% TP53 mutations = 29% | 2-y PFS 87% 2-y OS 100% | TP53 mutations but not MIPI or Ki-67 were associated with inferior PFS |
| NCT0352397544 (phase 1, n = 29 | Venetoclax, lenalidomide, and rituximab | High MIPI = 88% Blastoid = 21% Ki-67 ≥ 30% = 66% TP53 mutation = 17% | 2-y PFS 89% 2-y OS 92% | PFS inferior in patients with TP53 mutation (median: 9 mo vs not reached) |
| Trial . | Treatment(s) . | High-risk patients . | Outcomes . | |
|---|---|---|---|---|
| Overall . | High-risk patients . | |||
| IMCL-201529 (phase 2, n = 50) | Ibrutinib + rituximab | Blastoid and Ki-67 ≥ 30% excluded High MIPI = 38% TP53 mutations = 15% | 3-y PFS 93% 3-y OS 92% | High MIPI and TP53 aberrations associated with inferior PFS and OS. In TP53 mutated, mPFS of 39 mo vs not reached in wild type. |
| NCT0188056730 (phase 2, n = 50) | Ibrutinib + rituximab | Blastoid and Ki-67 ≥ 50% excluded High s-MIPI = 16% High MIPI-b = 28% TP53 aberrations = 17% | 3-y PFS 87% 3-y OS 94% | Ki-67 30-50% associated with lower ORR/CR rate. High s-MIPI associated with inferior PFS. TP53 aberrations associated with inferior OS but not PFS. |
| NCT0521418331 (phase 2, n = 50) | Acalabrutinib + rituximab | High s-MIPI = 22% Blastoid = 8% TP53 aberrations = 28% (23% with mutations) | 2-y PFS 92% 2-y OS 96% | Not reported |
| OAsIs I35,36 (phase 1/2, n = 15, treatment-naive cohort) | Ibrutinib, obinutuzumab, and venetoclax | High MIPI = 27% High MIPI-b = 55% TP53 mutation = 13% del17p deletion = 40% | 4-y PFS 80% 4-y OS 93% | Not reported |
| ACE-LY-10638 (phase 1b, n = 21) | Acalabrutinib, rituximab, and venetoclax | High s-MIPI = 19% Blastoid = 5% Ki-67 ≥ 30% = 48% | 2-y PFS 54% (95% when censored for COVID-19 deaths) 2-y OS 74% | Not reported |
| BOVen39 (phase 2, n = 25) | Zanubrutinib, obinutuzumab, and venetoclax | High MIPI = 68% Ki-67 ≥ 30% = 67% Blastoid = 20% TP53 mutated = 100% Del17p = 48% | 2-year PFS 72% 2-y PFS 75% | No significant association between disease-free survival and baseline factors, including Ki-67, morphology, and biallelic TP53 inactivation |
| NCT0386318443 (phase 2, n = 24) | Acalabrutinib, lenalidomide, and rituximab | High MIPI = 21% Ki-67 ≥ 30% = 29% TP53 mutations = 29% | 2-y PFS 87% 2-y OS 100% | TP53 mutations but not MIPI or Ki-67 were associated with inferior PFS |
| NCT0352397544 (phase 1, n = 29 | Venetoclax, lenalidomide, and rituximab | High MIPI = 88% Blastoid = 21% Ki-67 ≥ 30% = 66% TP53 mutation = 17% | 2-y PFS 89% 2-y OS 92% | PFS inferior in patients with TP53 mutation (median: 9 mo vs not reached) |