AN EVALUATION OF THE CLL-IPI SCORE AND COMPREHENSIVE PROGNOSTIC FACTOR ANALYSIS IN PATIENTS WITH R/R CLL IN IDELALISIB PHASE 3 RANDOMIZED STUDIES
Author(s): ,
Jacob D Soumerai
Affiliations:
Memorial Sloan-Kettering Cancer Center,New York, NY,United States
,
Jacqueline C Barrientos
Affiliations:
Hofstra North Shore-LIJ School of Medicine,Hempstead, NY,United States
,
Michael Hallek
Affiliations:
Department of Internal Medicine and Center of Integrated Oncology Cologne Bonn,University Hospital,Cologne,Germany
,
Thomas J Kipps
Affiliations:
University of California San Diego Moores Cancer Center,La Jolla,CA,United States
,
Jeffrey A Jones
Affiliations:
Ohio State University,Columbus, OH,United States
,
Guan Xing
Affiliations:
Gilead Sciences, Inc.,Foster City, CA,United States
,
Nai-Shun Yao
Affiliations:
Gilead Sciences, Inc.,Foster City, CA,United States
,
Loic Ysebaert
Affiliations:
Department of Haematology,Institut Universitaire du Cancer de Toulouse - Oncopôle,Toulouse,France
,
Stephan Stilgenbauer
Affiliations:
University of Ulm,Ulm,Germany
Andrew D Zelenetz
Affiliations:
Memorial Sloan-Kettering Cancer Center,New York, NY,United States
(Abstract release date: May 19, 2016) EHA Learning Center. Soumerai J. Jun 10, 2016; 133202
Dr. Jacob Soumerai
Dr. Jacob Soumerai

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Abstract
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Abstract: P214

Type: Poster Presentation

Presentation during EHA21: On Friday, June 10, 2016 from 17:15 - 18:45

Location: Poster area (Hall H)

Background
The International Prognostic Index for patients (pts) with chronic lymphocytic leukemia (CLL-IPI) is a scoring system with prognostic value for overall survival (OS) in untreated CLL (Bahlo J et al. Haematologica 2015; 100: 313), but has not been studied in relapsed/refractory (R/R) CLL or in the context of novel agents. The CLL-IPI is a risk-weighted model consisting of 5 risk factors: age (relative weight, 1), stage (1), β2-microglobulin (2), IGHV mutation status (2), and del(17p)/TP53 mutation (17p-/TP53M) (4). Since IDELA is active in CLL with 17p-/TP53M, which is a major contributor to the CLL-IPI, we hypothesized that IDELA would overcome the negative impact of a high CLL-IPI.

Aims
1)      To assess the prognostic utility of CLL-IPI in R/R CLL in IDELA phase 3 randomized trials
2)      To determine if IDELA overcomes the negative impact of a high CLL-IPI
3)      To identify independent risk factors for OS in pts with R/R CLL and in pts treated with IDELA

Methods
The CLL-IPI was analyzed among 460 pts with R/R CLL requiring treatment who received IDELA+rituximab (R) vs placebo+R (NCT01539512), or IDELA+ofatumumab (O) vs O (NCT01659021). Subgroup analyses were conducted in 274 pts treated with IDELA+R or IDELA+O (IDELA cohort) and 186 pts treated with R or O (Control). Median OS was estimated using the Kaplan-Meier method for the 4 CLL-IPI risk groups: low (score 0-1), intermediate (2-3), high (4-6), and very high (7-10). The log-rank test was used to compare survival distributions across CLL-IPI risk groups. Multivariate analyses of prognostic factors for OS were performed. Factors with a p-value of <0.1 in the univariate analysis (log-rank test) were included in the multivariate analyses (Cox proportion hazards model).

Results
Most pts with R/R CLL have very high (40.9%) and high risk CLL-IPI (49.6%), and intermediate (8.3%) and low risk CLL-IPI (1.3%) are rare. Notably, only 0.6% pts with R/R CLL were Rai 0/Binet A. At a median follow-up of 14.7 months, the CLL-IPI score was validated in pts with R/R CLL with significant differences in OS across CLL-IPI risk groups (p=0.0001).  In subgroup analyses, the CLL-IPI was prognostic for OS in the Control (p=0.0007) but not in the IDELA cohort (p=0.086). In the multivariate analyses: 17p-/TP53M, B2M, LDH and Karnofsky performance status (KPS) were independently prognostic for OS in pts with R/R CLL. While B2M, KPS and 17p-/TP53M were independently prognostic for OS in the Control cohort, only LDH and age were independently prognostic for OS in the IDELA cohort.
Multivariate analyses:R/R CLLIDELA CohortControl Cohort
Overall SurvivalHR (95% CI)P valueHR (95% CI)P valueHR (95% CI)P value
B2M > 3.52.29 (1.09, 4.8)0.02831.69 (0.64, 4.45)0.29123.29 (1.01, 10.69)0.0482
LDH elevated1.65 (1.15, 2.36)0.00641.73 (1.03, 2.89)0.03761.63 (0.97, 2.74)0.0665
Age > 651.44 (0.97, 2.15)0.0742.01 (1.11, 3.62)0.02020.94 (0.54, 1.65)0.8333
KPS  < 701.93 (1.33, 2.8)0.00051.47 (0.86, 2.52)0.1612.91 (1.71, 4.93)0.0001
17p-/TP53M1.63 (1.15, 2.32)0.00661.41 (0.86, 2.3)0.17321.88 (1.12, 3.15)0.0161
IGHV unmutated1.45 (0.88, 2.37)0.14481.48 (0.76, 2.86)0.24751.32 (0.61, 2.85)0.4764


Conclusion
Although low/intermediate-risk CLL-IPI is uncommon in R/R CLL, the CLL-IPI may be prognostic for OS in this population. These data suggest that IDELA overcomes the negative impact of high-risk CLL-IPI. While 17p-/TP53M, B2M, LDH and KPS were prognostic for OS in pts with R/R CLL, the current analysis indicates that only age and LDH may be prognostic for OS in pts treated with IDELA in combination with an anti-CD20 monoclonal antibody. Additional work is needed to develop adjusted risk models for pts with R/R CLL and for pts treated with targeted agents.



Session topic: CLL - Efficacy and safety of new treatments 1

Keyword(s): Chronic lymphocytic leukemia, International prognostic index, Randomized, Risk factor
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