Deletion 11q Abnormality in Patients with Chronic Lymphocytic Leukemia (CLL) May Not Have Poor Clinical Outcomes and Bulky Disease (clinical and radiological) At Presentation – Clinical Characteristics of (n=172) Previously Untreated Patients with CLL and del11q Cytogenetic Abnormality.
Authors: Jain Preetesh , Trinh Long Xuan , Benjamini Ohad , Lerner Susan , Wang Xuemei , Ferrajoli Alessandra , Burger Jan A. , Estrov Zeev , Wierda William G. , Kantarjian Hagop M. , O'Brien Susan , Abruzzo Lynne V. , Keating Michael J. 
Published: October 2019

Abstract
Abstract 2890

Introduction:
Del11q aberration is universally considered as an adverse prognostic marker in patients with CLL. However, large studies describing the clinical characteristics of del11q in CLL patients (pts) have never been reported. We studied the clinical features, outcomes and treatment responses among (172) previously untreated pts with CLL and del11q.

Methods:
This is a retrospective analysis of CLL pts (n=172) with del11q, who presented at our institution between 2003–2012. All pts signed an informed consent as per the declaration of Helsinki and IRB approval. Del11q was determined from bone marrow (BM) aspirate or blood samples by FISH (Fluorescent in-situ hybridization) technique. Detection of the 11q22.3 (ATM gene) on chromosome 11 used a multi-color FISH technique. Pts were divided into five categories – One – 57; del11q alone, Two – 105; del11q and del13q, others – 10 (4; del11q with +12, 1; del11q with del17p and 5; del11q, del13q with +12). Baseline bulky lymphadenopathy by CT scan or physical exam (PE) was also analysed. The probabilities of OS, PFS and TTFT (time to first treatment) were estimated using KM plots (log rank). PFS was assessed in 121 treated pts, from date of starting therapy to date of progression or death on therapy. The Cox proportional hazards regression model was used to assess the association between pt characteristics and OS, PFS or TTFT.

Results:
At the baseline, majority of pts with del11q were young (median age <60 years), males (81.4%) without very high white cell count (median 33.8 K/UL), absolute lymphocyte count – (median 27.1 K/UL) and β2 microglobulin (3 mg/L). Only 16.7% (n=28) patients had advanced Rai stage (3, 4). Majority were IGHV unmutated (n=112; 89.6%), CD38 high (n=88; 51.8%), Zap-70 high (n=100; 75.8%). Status of bulky disease was assessed by PE and baseline CT scans. Bulky disease by PE was observed in n=11 (6.4%) only. Baseline CT scans were performed for 108 patients out of whom only 16 patients (14.8%) had bulky disease. Thus, majority of del11q pts did not have bulky disease by PE or by CT scanning.
Analysis of time dependent variables was performed. Among the total 172 pts, 19 (11%) have died. and median time to death has not been reached (NR) - OS. 48/125 (38%) pts who were treated died or progressed and median PFS time was 49.2 months. Overall, 123 (71%) patients received therapy after initial presentation at MDACC. The median TTFT was 10.6 months. FCR based therapies were given in (91; 73 %) pts. Median PFS on FCR based therapy was 32 mo (Figure -1). CR was achieved in (70%; n=64) and overall response was 89%. Pts who received fludarabine based therapy had a significantly shorter TTFT as compared to non fludarabine based therapy (P<0.0001). Other pts (32) were treated with single agent rituximab and lenalidomide protocols.
To address whether del11q has any influence over presence of deletion 13 q abnormality we compared (del11q alone; n=57) vs (del11 and del13q; n=105) patients. Patients with sole del11q had significant proportions of younger patients, lesser WBC count, and ALC and β2 microglobulin. Furthermore, there was no significant difference in OS, PFS and TTFT among the two categories. In the multivariate analysis for OS and PFS among the two categories, β2 microglobulin was significantly predictive of increased risk of death or progression among the two categories and FISH categories were not significantly predictive of OS or PFS or TTFT. Bulky disease by PE (and not by CT scan) was significantly associated with a shorter TTFT (HR=2.93; 95%CI -1.5–5.69 and P=0.002).
Furthermore, a separate cohort of (n=500) patients with sole del13q was compared with del11q alone (n=57) and del11q with del13q (n=105). There was no significant difference in OS but the TTFT was significantly shorter in del11q alone (data not shown).

Conclusions:
We describe the clinical features of del11q in CLL patients. This study suggests that occurrence of del11q is frequent with del13q abnormality. The majority of patients with del11q did not have bulky disease as assessed by PE or by CT scan. Presence of bulky disease by PE predicted for a shorter TTFT. β2 microglobulin level significantly predicted for OS and PFS. FCR based therapy has good responses. Del11q is similar to del13q in terms of OS, PFS and TTFT. Del11q may not have very poor adverse outcomes in patients with CLL inspite of a shorter TTFT.

Disclosures:
Burger: Pharmacyclics: Consultancy, Research Funding. Wierda:Abbott: Research Funding; Genentech: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; AmGen: Research Funding; Merck: Consultancy; Celgene: Consultancy; Pharmacyclics: Consultancy; Genzyme: Consultancy. Kantarjian:Genzyme: Research Funding.