Chemotherapy-free novel agents and combinations in R/R MCL
| Regimen . | Phase . | N . | Median age, y (range) . | ORR (%) . | CR (%) . | PFS . | OS . | Predictive biomarkers . | MRD negativity . | References . |
|---|---|---|---|---|---|---|---|---|---|---|
| Single agent | ||||||||||
| Bortezomib | 2 | 33 | 65 (42-89) | 32 | 8 | Median, 6.5 mo | Median, 23.5 mo | Ki-67 | N/R | 48 |
| Lenalidomide | 2 | 134 | 67 (43-83) | 28 | 8 | Median, 4 mo | Median, 21 mo | Ki-67 | N/R | 37 |
| 3 | 170 | 68.5 (44-88) | 40 | 5 | Median, 8.7 mo | Median, 27.9 mo | N/R | N/R | 35 | |
| Ibrutinib | 2 | 111 | 68 (40-84) | 68 | 21 | Median, 13.9 mo | Median, 22.5 mo | N/R | N/R | 38 |
| 2/3 | 370 | 68 (N/R) | 66 | 20 | Median, 12.8 mo | Median, 25 mo | sMIPI, blastoid histology | N/R | 39,49 | |
| Acalabrutinib | 2 | 124 | 68 (61-75) | 81 | 40 | 1-y rate, 72% | 1-y rate, 87% | N/R | N/R | 41 |
| Zanbrutinib | 2 | 86 | N/R (18-75) | 84 | 59 | 24-wk rate, 82% | N/R | N/R | N/R | 42 |
| Venetoclax | 1 | 28 | 72 (35-85) | 75 | 21 | Median, 14 mo | 1-y rate, 82% | N/R | N/R | 44 |
| Lenalidomide combinations | ||||||||||
| Lenalidomide-rituximab | 2 | 52 | 66 (46-85) | 57 | 36 | Median, 11 mo | Median, 24 mo | N/R | N/R | 36 |
| Ibrutinib combinations | ||||||||||
| Ibrutinib-rituximab | 2 | 50 | 67 (45-86) | 88 | 44 | Median, 43 mo; 3-y rate, 68% | Median, 14 mo; 3-y rate, 69% | MIPI, Ki-67, and blastoid histology | N/R | 40 |
| Ki-67 <50%: N/R; Ki-67 ≥50%: 8 mo | Ki-67 <50%, 81%; Ki-67 ≥50%, 27% | |||||||||
| Ibrutinib-venetoclax | 2 | 23 | 68 (47-81) | 71 | 71 | 18-mo rate, 57% | 18-mo rate, 74% | Ki-67 | PB 56%, BM 84% | 50 |
| Ibrutinib-palbociclib | 1 | 27 | 65 (42-81) | 67 | 37 | 2-y rate, 59% | 2-y rate, 61% | N/R | N/R | 45 |
| Ibrutinib-lenalidomide-rituximab | 2 | 50 | 69 (45-85) | 76 | 56 | Median, 16 mo | Median, 22 mo | MIPI and MRD correlate with PFS | 6-mo: PB, 56% and BM, 43%; 12-mo: PB, 58% and BM, 68% | 43 |
| Regimen . | Phase . | N . | Median age, y (range) . | ORR (%) . | CR (%) . | PFS . | OS . | Predictive biomarkers . | MRD negativity . | References . |
|---|---|---|---|---|---|---|---|---|---|---|
| Single agent | ||||||||||
| Bortezomib | 2 | 33 | 65 (42-89) | 32 | 8 | Median, 6.5 mo | Median, 23.5 mo | Ki-67 | N/R | 48 |
| Lenalidomide | 2 | 134 | 67 (43-83) | 28 | 8 | Median, 4 mo | Median, 21 mo | Ki-67 | N/R | 37 |
| 3 | 170 | 68.5 (44-88) | 40 | 5 | Median, 8.7 mo | Median, 27.9 mo | N/R | N/R | 35 | |
| Ibrutinib | 2 | 111 | 68 (40-84) | 68 | 21 | Median, 13.9 mo | Median, 22.5 mo | N/R | N/R | 38 |
| 2/3 | 370 | 68 (N/R) | 66 | 20 | Median, 12.8 mo | Median, 25 mo | sMIPI, blastoid histology | N/R | 39,49 | |
| Acalabrutinib | 2 | 124 | 68 (61-75) | 81 | 40 | 1-y rate, 72% | 1-y rate, 87% | N/R | N/R | 41 |
| Zanbrutinib | 2 | 86 | N/R (18-75) | 84 | 59 | 24-wk rate, 82% | N/R | N/R | N/R | 42 |
| Venetoclax | 1 | 28 | 72 (35-85) | 75 | 21 | Median, 14 mo | 1-y rate, 82% | N/R | N/R | 44 |
| Lenalidomide combinations | ||||||||||
| Lenalidomide-rituximab | 2 | 52 | 66 (46-85) | 57 | 36 | Median, 11 mo | Median, 24 mo | N/R | N/R | 36 |
| Ibrutinib combinations | ||||||||||
| Ibrutinib-rituximab | 2 | 50 | 67 (45-86) | 88 | 44 | Median, 43 mo; 3-y rate, 68% | Median, 14 mo; 3-y rate, 69% | MIPI, Ki-67, and blastoid histology | N/R | 40 |
| Ki-67 <50%: N/R; Ki-67 ≥50%: 8 mo | Ki-67 <50%, 81%; Ki-67 ≥50%, 27% | |||||||||
| Ibrutinib-venetoclax | 2 | 23 | 68 (47-81) | 71 | 71 | 18-mo rate, 57% | 18-mo rate, 74% | Ki-67 | PB 56%, BM 84% | 50 |
| Ibrutinib-palbociclib | 1 | 27 | 65 (42-81) | 67 | 37 | 2-y rate, 59% | 2-y rate, 61% | N/R | N/R | 45 |
| Ibrutinib-lenalidomide-rituximab | 2 | 50 | 69 (45-85) | 76 | 56 | Median, 16 mo | Median, 22 mo | MIPI and MRD correlate with PFS | 6-mo: PB, 56% and BM, 43%; 12-mo: PB, 58% and BM, 68% | 43 |