Summary of multiple regression analyses for durability of response
| Variable . | HR (95% CI] for relapse risk . | |||||
|---|---|---|---|---|---|---|
| Pretreatment variables only . | Pretreatment variables plus response depth (PR vs CR) at 9 mo . | Pretreatment variables plus MRD status (pos vs U) at 24 mo . | ||||
| All patients (n = 323) . | 400 mg monotherapy (n = 250) . | All patients (n = 311) . | 400 mg monotherapy (n = 242) . | All patients (n = 187) . | 400 mg monotherapy (n =)159 . | |
| Max node size, cm | ||||||
| ≥5 to <10 | 2.5(1.7-3.7) | 2.4 (1.5-3.7) | 2.1(1.4-3.3) | 2.1 (1.3-3.3) | 2.9(1.7-5.1) | 2.8 (1.6-5.1) |
| ≥10 | 2.8(1.7-4.6) | 2.7 (1.5-4.8) | 2.3(1.3-3.9) | 2.4 (1.4-4.3) | 3.6(1.6-7.9) | 3.0 (1.4-6.8) |
| Prior therapies | ||||||
| 2 to 3 | NI | NI | NI | NI | NI | NI |
| >3 | NI | NI | NI | NI | NI | NI |
| Fludarabine refractory disease | 1.5 (1.1-2.2) | NI | 1.5 (1.1-2.2) | NI | 1.0 (0.6-1.8)* | NI |
| Prior BCRi exposure | NI | NI | NI | NI | NI | NI |
| BCRi refractory disease | 2.5 (1.5-4.1)† | 1.9(1.1-3.3) | 2.3 (1.4-3.9)† | 1.9(1.1-3.2) | 3.0 (1.6-5.8)† | 2.6(1.4-5.0) |
| TP53 mutation and/or 17p deletion | 1.8(1.2-2.5) | NI | 1.8(1.3-2.7) | NI | 1.9(1.0-3.4) | NI |
| 13q deletion | NI | NI | NI | NI | NI | NI |
| NOTCH1 mutation | 1.8(1.1-3.0) | NI | 2.0(1.2-3.3) | NI | 2.6(1.1-6.2) | NI |
| IGHV unmutated | 2.1 (1.0-4.3) | NI | NI | NI | NI | NI |
| Monotherapy vs combination‡ | 0.8 (0.4-1.5) | — | — | — | — | — |
| PR/nPR vs CR/CRi at 9 mo¶ | — | — | 2.1 (1.1-4.0) | 3.3(1.0-10.5) | — | — |
| PB MRD-pos vs U-MRD at 24 mo¶ | — | — | — | — | 3.0(1.7-5.2) | 3.4(1.9-6.3) |
| Variable . | HR (95% CI] for relapse risk . | |||||
|---|---|---|---|---|---|---|
| Pretreatment variables only . | Pretreatment variables plus response depth (PR vs CR) at 9 mo . | Pretreatment variables plus MRD status (pos vs U) at 24 mo . | ||||
| All patients (n = 323) . | 400 mg monotherapy (n = 250) . | All patients (n = 311) . | 400 mg monotherapy (n = 242) . | All patients (n = 187) . | 400 mg monotherapy (n =)159 . | |
| Max node size, cm | ||||||
| ≥5 to <10 | 2.5(1.7-3.7) | 2.4 (1.5-3.7) | 2.1(1.4-3.3) | 2.1 (1.3-3.3) | 2.9(1.7-5.1) | 2.8 (1.6-5.1) |
| ≥10 | 2.8(1.7-4.6) | 2.7 (1.5-4.8) | 2.3(1.3-3.9) | 2.4 (1.4-4.3) | 3.6(1.6-7.9) | 3.0 (1.4-6.8) |
| Prior therapies | ||||||
| 2 to 3 | NI | NI | NI | NI | NI | NI |
| >3 | NI | NI | NI | NI | NI | NI |
| Fludarabine refractory disease | 1.5 (1.1-2.2) | NI | 1.5 (1.1-2.2) | NI | 1.0 (0.6-1.8)* | NI |
| Prior BCRi exposure | NI | NI | NI | NI | NI | NI |
| BCRi refractory disease | 2.5 (1.5-4.1)† | 1.9(1.1-3.3) | 2.3 (1.4-3.9)† | 1.9(1.1-3.2) | 3.0 (1.6-5.8)† | 2.6(1.4-5.0) |
| TP53 mutation and/or 17p deletion | 1.8(1.2-2.5) | NI | 1.8(1.3-2.7) | NI | 1.9(1.0-3.4) | NI |
| 13q deletion | NI | NI | NI | NI | NI | NI |
| NOTCH1 mutation | 1.8(1.1-3.0) | NI | 2.0(1.2-3.3) | NI | 2.6(1.1-6.2) | NI |
| IGHV unmutated | 2.1 (1.0-4.3) | NI | NI | NI | NI | NI |
| Monotherapy vs combination‡ | 0.8 (0.4-1.5) | — | — | — | — | — |
| PR/nPR vs CR/CRi at 9 mo¶ | — | — | 2.1 (1.1-4.0) | 3.3(1.0-10.5) | — | — |
| PB MRD-pos vs U-MRD at 24 mo¶ | — | — | — | — | 3.0(1.7-5.2) | 3.4(1.9-6.3) |
All variables included in univariate analyses were tested in the multiple regressions. Covariates selected by stepwise regression are reported, and the effects of monotherapy vs combination, PR/nPR vs CR/CRi at 9 mo, and PB MRD-pos vs U-MRD at 24 mo were added as a variable of interest after model selection, separately. Those bolded are significant; and italicized if confirmed as significant in a sensitivity analysis that only included patients in whom all data for all variables were informative (supplemental Table 6).
NI, not included in final model; U-MRD, minimal residual disease not detected by flow cytometry at 10−4 leukemic cell cutoff; MRD-pos, detectable MRD; —, not tested/not applicable; PB, peripheral blood.
Significant pretreatment variable that is not statistically significant when a posttreatment response variable is included in the model.
In these 3 instances, prior BCRi exposure had higher priority in the model outputs of the sensitivity analyses than BCRi-refractoriness, and was statistically significant.
After pretreatment variables of significance in multiple regression analyses were identified, the treatment variable of venetoclax monotherapy or combination with rituximab was added into the Cox regression model.
After pretreatment variables of significance in multiple regression analyses were identified, the posttreatment response variable of either PR or CR at 9 months or MRD-pos or U-MRD status at 24 months was added into the Cox regression model.