Table 2.
Association of Patient Characteristics With Progression-free Survival in Uni- and Multivariate Analysis
| Variable | n | Univariate HR (95% CI) |
P-value | High-risk Balancer Coefficients (Lasso Model) |
Confirmatory Lasso Model Coefficients |
|---|---|---|---|---|---|
| Response to bridging (SD/PD vs CR/PR or no bridging) | 346 | 2.1 (1.6-2.8) | <0.0001 |
0.35 (nonresponse) |
-a |
| Ferritin (fold change ULN, log2) | 332 | 1.2 (1.1-1.4) | <0.0001 | 0.10 | -a |
| CAR-T product (Tisa-cel vs Axi-cel) | 374 | 1.8 (1.4-2.3) | <0.0001 | -a | 0.04 (Tisa-cel) |
| CRP (fold change ULN, log2) | 371 | 1.1 (1.1-1.2) | <0.0001 | 0.01 | -a |
| ECOG (0-1 vs 2-4) | 374 | 1.9 (1.3-2.6) | 0.0002 | - | - |
| Interval Apheresis-CAR-T (mo, log2) |
374 | 1.5 (1.2-1.9) | 0.001 | - | - |
| Presence of END | 374 | 1.6 (1.1-2.1) | 0.005 | - | - |
| Interval Indication-CAR-T (mo, log2) |
374 | 1.4 (1.1-1.8) | 0.006 | - | - |
| LDH (fold change ULN, log2) | 353 | 1.3 (1.1-1.5) | 0.006 | - | - |
| Prior therapy lines (incl. H&B, log2) | 372 | 1.3 (1-1.7) | 0.020 | - | - |
| Ann Arbor Stage (III/IV vs I/II) | 374 | 1.5 (1.1-2.1) | 0.020 | - | - |
| Response to previous therapy (refractory vs relapsed) | 371 | 1.4 (1.0-1.9) | 0.039 | - | - |
| Diagnosis (LBCL vs transformed LBCL) |
374 | 1.4 (0.99-1.9) | 0.060 | - | - |
| Bulky disease | 335 | 1.4 (0.96-2.1) | 0.082 | - | - |
| HR balancer | 277 | 1.11 | |||
| History of/active CNS disease | 314 | 1.4 (0.92-2.2) | 0.12 | ||
| Interval initial diagnosis-indication (years, log2) | 175 | 0.96 (0.89-1) | 0.25 | ||
| History of auto-SCT | 372 | 0.85 (0.63-1.2) | 0.29 | ||
| Age (years) | 373 | 1 (0.98-1) | 0.36 | ||
| Interval Initial diagnosis – first relapse (years, log 2) | 175 | 0.94 (0.83-1.1) | 0.36 | ||
| History of allo-SCT | 372 | 1.2 (0.5-2.9) | 0.68 | ||
| Prior therapy lines (excl. H&B, log2) | 372 | 1 (0.92-1.1) | 0.93 | ||
| Interval Indication – apheresis (mo, log2) |
361 | 1 (0.85-1.3) | 0.77 |
Factors associated with PFS in univariate and multivariate analysis. For multivariate analysis, only variables with P ≤ 0.1 in univariate Cox regression analysis were included. CAR T-cell product, however, was omitted for the definition of the multivariate model to identify product-independent variables with significant influence on PFS. A Lasso penalized regression model was used. Missing ferritin values at the time of lympho depletion were replaced with values from apheresis or indication (n = 12) for multivariate analysis. A confirmatory Lasso model was calculated using all variables identified in univariate analysis with the exception of those already included in the HR balancer (response to bridging, ferritin, and CRP), but now including the used CAR T-cell product to allow an estimate of the influence of product choice. P values <0.05 in univariate analysis and Lasso coefficients with relevance for the multivariate model are highlighted in bold.
aExcluded from Lasso analysis.
CAR = chimeric antigen receptor; CI = confidence interval; CNS = central nervous system; CR = complete response; CRP = C-reactive protein; ECOG = Eastern Cooperative Oncology Group performance status; END = extranodal disease; H&B = holding and bridging therapy; HR = hazard ratio; LDH = lactate dehydrogenase; mo = months; PD = progressive disease; PFS = progression-free survival; PR = partial response; SCT = stem cell transplantation; SD = stable disease; Tisa-cel = tisagenlecleucel; ULN = upper limit of normal.