•ROC curves (Youden index) identified optimal cut-offs for progression/death at 12 months; AUC was additionally estimated at 6, 24 and 36-month PFS landmarks (supplementary analysis).

•Associations with TTFT were assessed by Spearman correlation.

•Event rates were compared with Fisher’s exact test.

•BTK+BCL2 combination patients were analyzed separately and are not included here.

 

 

MATERIALS 

Two-step, retrospective design. Two dedicated, partially overlapping databases were analyzed sequentially.

Step 1 — Population-level analysis (TTFT). The full first-line cohort (n=110), including all first-line regimens (BTK inhibitors, chemoimmunotherapy, BCL2i-based combinations), was used to test whether inflammatory markers at diagnosis (NMR, CD4/CD8 ratio, RDW/albumin, ESR) were associated with time to first treatment (TTFT), by Spearman correlation. 

Step 2 — BTKi subgroup analysis (PFS/OS). Within the subgroup of patients treated with a BTK inhibitor at any line (n=134), the same markers were re-evaluated for their association with progression-free survival (PFS) and overall survival (OS) on BTK therapy, using ROC-derived cut-offs (Youden index) at the 12-month landmark. 

This sequential design first characterizes TTFT determinants at the population level, then focuses on the BTKi-treated subgroup to test whether the same markers also carry prognostic value for PFS/OS.

 

RESULTS 

STEP 1 — TTFT IN THE FULL FIRST-LINE POPULATION (n=110)

TTFT in the full first-line population (n=110). Median time to first treatment 26.2 months (IQR 5.5–59.9). None of the inflammatory markers assessed at diagnosis were associated with TTFT: NMR (ρ=0.14, p=0.21), RDW/albumin (ρ=−0.12, p=0.30), ESR (ρ=−0.10, p=0.51), CD4/CD8 (ρ=0.14, p=0.26).

Exploratory signal in the BTKi subgroup. Restricted to BTK inhibitor–treated patients (n=134; time to BTK initiation, median 21.0 months, IQR 0–87), ESR correlated with shorter TTFT (ρ=−0.27, p=0.033); NMR and RDW/albumin did not. As this did not replicate in the full population above, it should be treated as hypothesis-generating.

Overall survival (BTKi subgroup). 47 deaths / 124 patients with follow-up (median 45.3 months). None of the three markers were associated with OS, either as a continuous correlate with survival time or as a binary cut-off (all p>0.30, including at the 12-month landmark).

STEP 2 — BTKi SUBGROUP (n=134): PFS & OS — KEY FINDING - 

PATIENT COHORTS AT A GLANCE — BTKi (any line) vs. first-line, all therapies

Key finding: an elevated RDW/albumin ratio (>4.06) at BTK initiation was associated with a 6-fold higher risk of progression or death within 12 months (30.4% vs 6.8%, OR 6.0, p=0.009). ESR showed a concordant, non-significant trend; NMR was not discriminative.

Supplementary landmark analysis (6/12/24/36 months, Fig. 3): AUC for RDW/albumin and ESR was highest early (6–12 months) and declined progressively by 36 months, while NMR remained uninformative at every landmark — indicating the signal is strongest for near-term progression risk.

 

CONCLUSIONS