The CLL-IPI score, which combines genetic, biochemical, and clinical parameters, represents a simple worldwide model able to refine risk stratification for CLL patients. This score, developed in the era of chemo-immunotherapy, has not been gauged extensively in R/R-CLL patients treated with novel targeted agents, such as BCR and BCL2 inhibitors. Soumerai et al (Lancet Hematol 2019) assembled a novel risk model for OS in the setting of R/R-CLL receiving targeted therapies in clinical trials. This model, consisting of four accessible markers (β2M, LDH, Hb, and time from initiation of last therapy; BALL score), is able to cluster 3 groups of CLL patients with significantly different OS. This multicenter, observational retrospective study aimed to validate the proposed Soumerai (BALL) and/or CLL-IPI scores for R/R-CLL real-world patients treated with idelalisib and rituximab (IDELA-R). The primary objectives were to determine whether: i) the CLL-IPI retains its prognostic power also in R/R patients treated with IDELA-R; ii) the BALL score is of prognostic value for IDELA-treated R/R-CLL patients, and iii) the BALL score is predictive of PFS. This study, sponsored by Gilead (ISR#IN-IT-312-5339), included CLL patients collected from 12 Italian centers, who received IDELA-R (idelalisib 150 mg b.i.d. and a total of 8 rituximab infusions intravenously) outside clinical trials as salvage therapy with available data for the calculation of the CLL-IPI and BALL scores at the time of treatment start. OS was estimated for all subgroups of both scores. Additionally, risk-specific PFS was assessed. Kaplan-Meier curve, log-rank test, and Cox regression analyses were performed. The prognostic accuracy of the predictive model was assessed by Harrell's C-index. Overall, 120 CLL patients were included in this analysis. The majority of patients were Binet stage B and C (94.2%). The median age was 75 years and 83 cases (69.2%) were male. The median number of previous therapies was 3 (range 1-9) Baseline patient features are listed in Table 1. After a median follow-up of 1.6 years (1 month to 5.8 years), 33 patients had died and 39 experienced an event (death or progression). CLL-IPI scoring (115/120 evaluable cases) indicated that 6 patients (5.2%) were classified as low-risk, 24 (20.9%) as intermediate-risk, 58 (50.4%) as high-risk, and 27 (23.5%) as very high-risk. Stratification of patients according to the CLL-IPI score did not allow prediction of significant differences in OS. Thus, low-risk patients had a 2-year OS probability of 75% (HR=1), with an intermediate-risk of 68% (HR=2.9, 95%CI 0.37-23.3, P=0.3), high-risk of 83% (HR=1.58, 95%CI 0.2-12.5, P=0.66), and very high-risk of 63% (HR=5.9, 95%CI 0.78-45.2, P=0.86). Next, we tested a modified CLL-IPI by assigning a more balanced score to the original CLL-IPI variables (Soumerai et al, Leukemia Lymphoma 2019), partially overlapping previous results. Specifically, modified CLL-IPI high-risk group showed a significantly different OS as compared with intermediate- and low-risk groups. However, differently from the original report no difference was observed between low- and intermediate-risk). According to the BALL score (120/120 evaluable cases), 33 patients (27.5%) were classified as low-risk, 68 (56.7%) as intermediate-risk, and 19 (15.8%) as high-risk. Stratification of patients according to the BALL score predicted significant differences in terms of OS. Thus, low-risk patients had a 2-year OS probability of 92% (HR=1), intermediate-risk of 76% (HR=5.47, 95%CI 1.3-23.7, P=0.023), and high-risk of 54% (HR=15.1, 95%CI 3.4-67, P<0.0001) (Figure 1). Harrell's C-statistic was 0.68 (P<0.001) for predicting OS. To note, BALL score failed to significantly stratify patients in terms of PFS. As for Soumerai et al (Leukemia Lymphoma 2019), the original CLL-IPI score did not retain discriminative power in term of OS in R/R-CLL patients receiving IDELA-R. The modified CLL-IPI failed to stratify low- and intermediate-risk groups, likely due to the number of cases analysed in the current cohort and the heterogeneous IDELA-containing regimens included in the Soumerai study (Soumerai et al, Leukemia Lymphoma 2019). The CLL-IPI was designed for CLL patients treated with first-line chemo-immunotherapy. Herein, we confirm the prognostic power of the BALL score in this real-world series for OS, while losing the predictive impact of patient outcomes in terms of PFS.
Disclosures
Mauro: Gilead: Consultancy, Research Funding; Jannsen: Consultancy, Research Funding; Shire: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Roche: Consultancy, Research Funding. Coscia:Abbvie: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Varettoni:ABBVIE: Other: travel expenses; Roche: Consultancy; Janssen: Consultancy; Gilead: Other: travel expenses. Rossi:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria, Other: Scientific advisory board; Janseen: Honoraria, Other: Scientific advisory board; Roche: Honoraria, Other: Scientific advisory board; Astra Zeneca: Honoraria, Other: Scientific advisory board. Gaidano:AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sunesys: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
Shear Wave Elastography and Thyroid Imaging Reporting and Data System (TIRADS) for the Risk Stratification of Thyroid Nodules—Results of a Prospective Study
