Response assessment by CXCR4, TP53, and TERT mutational statuses in patients treated with zanubrutinib with MYD88MUT
| Patients with MYD88MUT treated with zanubrutinib (n = 98) . | |||||||
|---|---|---|---|---|---|---|---|
| . | CXCR4WT (n = 65) . | CXCR4FS (n = 19) . | CXCR4NS (n = 14) . | TP53WT (n = 72) . | TP53MUT (n = 26) . | TERTWT (n = 88) . | TERTMUT (n = 10) . |
| VGPR or better, n (%)∗ | 29 (44.6) | 5 (26.3) | 2 (14.3) | 27 (37.5) | 9 (34.6) | 35 (39.8) | 1 (10.0) |
| OR (95% CI) | - | 0.51 (0.16, 1.66) | 0.24 (0.04, 1.26) | - | 1.27 (0.46, 3.52) | - | 0.25 (0.02, 2.26) |
| P value | - | .269 | .093 | - | .636 | - | .219 |
| Major response, n (%)∗ | 54 (83.1) | 14 (73.7) | 12 (85.7) | 59 (81.9) | 21 (80.8) | 73 (83.0) | 7 (70.0) |
| OR (95% CI) | - | 0.66 (0.18, 2.36) | 1.52 (0.25, 9.01) | - | 1.01 (0.29, 3.47) | - | 0.47 (0.09, 2.39) |
| P value | - | .524 | .639 | - | .978 | - | .362 |
| Time to VGPR or better, median (min, max), mo | 6.5 (1.9, 42.0) | 11.1 (2.8, 26.0) | 10.3 (9.4, 11.1) | 6.5 (1.9, 42.0) | 11.1 (3.0, 26.0) | 6.7 (1.9, 49.8) | 22.2 (22.2, 22.2) |
| Time to major response, median (min, max), mo | 2.8 (0.9, 28.5) | 2.9 (1.8, 49.8) | 4.1 (1.0, 38.7) | 2.8 (0.9, 49.8) | 2.8 (1.0, 5.6) | 2.8 (0.9, 49.8) | 3.7 (1.8, 22.2) |
| PFS† | |||||||
| Event-free rate at 42 months, % | 81.3 | 76.4 | 66.7 | 84.6 | 62.0 | 83.4 | 37.5 |
| Median, mo | NE | NE | NE | NE | NE | NE | 25.0 |
| HR (95% CI) | - | 0.62 (0.17, 2.25) | 0.67 (0.15, 2.88) | - | 2.20 (0.81, 5.98) | - | 5.78 (1.75, 19.13) |
| P value | .473 | .598 | .120 | - | .004 | ||
| Patients with MYD88MUT treated with zanubrutinib (n = 98) . | |||||||
|---|---|---|---|---|---|---|---|
| . | CXCR4WT (n = 65) . | CXCR4FS (n = 19) . | CXCR4NS (n = 14) . | TP53WT (n = 72) . | TP53MUT (n = 26) . | TERTWT (n = 88) . | TERTMUT (n = 10) . |
| VGPR or better, n (%)∗ | 29 (44.6) | 5 (26.3) | 2 (14.3) | 27 (37.5) | 9 (34.6) | 35 (39.8) | 1 (10.0) |
| OR (95% CI) | - | 0.51 (0.16, 1.66) | 0.24 (0.04, 1.26) | - | 1.27 (0.46, 3.52) | - | 0.25 (0.02, 2.26) |
| P value | - | .269 | .093 | - | .636 | - | .219 |
| Major response, n (%)∗ | 54 (83.1) | 14 (73.7) | 12 (85.7) | 59 (81.9) | 21 (80.8) | 73 (83.0) | 7 (70.0) |
| OR (95% CI) | - | 0.66 (0.18, 2.36) | 1.52 (0.25, 9.01) | - | 1.01 (0.29, 3.47) | - | 0.47 (0.09, 2.39) |
| P value | - | .524 | .639 | - | .978 | - | .362 |
| Time to VGPR or better, median (min, max), mo | 6.5 (1.9, 42.0) | 11.1 (2.8, 26.0) | 10.3 (9.4, 11.1) | 6.5 (1.9, 42.0) | 11.1 (3.0, 26.0) | 6.7 (1.9, 49.8) | 22.2 (22.2, 22.2) |
| Time to major response, median (min, max), mo | 2.8 (0.9, 28.5) | 2.9 (1.8, 49.8) | 4.1 (1.0, 38.7) | 2.8 (0.9, 49.8) | 2.8 (1.0, 5.6) | 2.8 (0.9, 49.8) | 3.7 (1.8, 22.2) |
| PFS† | |||||||
| Event-free rate at 42 months, % | 81.3 | 76.4 | 66.7 | 84.6 | 62.0 | 83.4 | 37.5 |
| Median, mo | NE | NE | NE | NE | NE | NE | 25.0 |
| HR (95% CI) | - | 0.62 (0.17, 2.25) | 0.67 (0.15, 2.88) | - | 2.20 (0.81, 5.98) | - | 5.78 (1.75, 19.13) |
| P value | .473 | .598 | .120 | - | .004 | ||
Response rates, time to response, and PFS were compared according to the mutational status of CXCR4, TP53, and TERT genes in 92 patients with MYD88MUT WM treated with ibrutinib and 98 patients with MYD88MUT WM treated with zanubrutinib, respectively. MYD88 status was assessed by a polymerase chain reaction–based assay, with a total of 190 patients with MYD88MUT WM.
CI, confidence interval; max, maximum; min, minimum; NE, not estimable; OR, odds ratio.
Odds ratio and P values were estimated using a logistic regression model with CXCR4 (WT, NS, and FS), TP53 (WT and MUT), and TERT (WT and MUT) mutational status as covariates.
Median PFS was estimated by Kaplan-Meier method; HR and P values were estimated using a Cox regression model with CXCR4 (WT, FS, and NS), TP53 (WT and MUT), and TERT (WT and MUT) mutational statues as covariates. WT is the reference group.