Page 136 - Haematologica July

1214
A. Cuneo et al.
A
B
C
Figure 2. Overall survival (OS) of patients treated with bendamustine and rituximab (BR) second-line. OS of all 237 patients (A), by stage (B) and by response to BR (C).
P=0.146
Months from treatment start
only predictive factor with borderline statistical signifi- cance of shorter survival (Online Supplementary Table S5). When restricting the analysis to patients who had received CIT front-line (Table 5), the ibrutinib cohort and the BR cohort were comparable in terms of median age, ECOG PS, ORR rate to first-line treatment, and frequency of U- IGHV (available in a proportion of cases), although with a slightly shorter interval between first- and second-line treatment in the ibrutinib cohort (interval <36 months in 76.1% vs. 59.1% of patients) and a higher number of patients with 17p deletion in the ibrutinib cohort (36.1% vs. 14.8%). When excluding patients with del(17p) from the analysis, there was no significant difference in OS between the 39 patients treated with ibrutinib (63% alive at 36 months, 95%CI: 48.8-81.6) and the 92 patients treat- ed with BR (74.4% alive at 36 months, 95%CI: 64.7-85.5 (Figure 3). A subanalysis of the OS in patients with intact 17p and with a less than 36-month interval between first- line and first salvage treatment in the BR cohort (n=55) and in the ibrutinib cohort (n=33) showed no significant difference, with 72.6% of patients alive at three years with BR (95%CI: 60.1-87.7) and 59.8% alive at three years with ibrutinib (95%CI: 44.2-80.7) (P=0.19).
Discussion
Accepting the limitations of retrospective analyses, we set out to collect data on the efficacy of BR, one of the most widely utilized CIT regimens in CLL. We elected to include in this study only patients who received second- line treatment with BR given the limited availability of published data in this setting in order to contribute new information that may assist clinicians in the selection of the most appropriate first salvage treatment in CLL. To minimize possible selection biases and imprecise report- ing of data: i) we encouraged clinicians to report all
Figure 3. Indirect comparison of overall survival in 39 patients treated second- line with ibrutinib and in 92 patients treated with bendamustine and rituximab (Benda+RTX). All patients had intact 17p and received chemoimmunotherapy as front-line therapy.
patients who initiated BR treatment; ii) we analyzed the reported data according to the intention-to-treat principle; and iii) we performed computerized and manual consis- tency checks on each case report form.
Besides PFS, we included objective efficacy measures of the BR regimen, such as OS and the TTNT. Keeping in mind that response assessment may vary among centers and that bone biopsy was not routinely performed, we agreed to record as “response” what each treating clinician graded as “partial” or “complete” remission.
The patient population who received BR included in this study closely resembled the typical CLL patient seen in daily clinical practice in terms of age, PS and comorbidi- ties.14 The number of patients who completed the planned treatment (69.6%) was in line with a previous prospective phase-II GIMEMA study, where 76% of R/R CLL patients completed treatment.16 This finding suggests that there
haematologica | 2018; 103(7)