De Novo Deletion 17p13.1 Chronic Lymphocytic Leukemia Shows Significant Clinical Heterogeneity: The MD Anderson/Mayo Clinic Experience.

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In order to characterize the clinical course of patients (pts) with deletion 17p13.1 (17p-) CLL, we identified 100 consecutive treatment-naïve pts with 17p- from the MD Anderson Cancer Center (MDACC, n=61) and Mayo Clinic (n=39) clinical databases. The diagnosis of 17p- was established by FISH with a median time from initial diagnosis to FISH documenting 17p- of 9 months. Median age was 64 yrs (60 for MDACC pts & 70 for Mayo pts) and Rai stage was 0, 1–2 and 3–4 in 34%, 49% and 17% pts respectively. 17p- was the sole FISH abnormality in 29%. Unmutated IgVH and ZAP-70 positivity were present in 30/62 and 54/84 patients respectively. <<<TIME TO FIRST THERAPY>>> 69 asymptomatic pts were followed until they developed progressive disease requiring therapy as defined by the NCIWG 96 criteria. The 2 year actuarial risk of progression to initiation of therapy was 43% (46% for MDACC pts & 36% for Mayo pts). Only 2 of 10 pts with stable disease >2 years progressed on prolonged follow-up of up to 54 months. Two pts with baseline 17p- in 10% and 13% of nuclei lost their 17p- clone after 23 and 41 months. Independent predictors of shorter time to treatment were Rai stage > 0 (hazard ratio 7.2) and unmutated IgVH (HR 5.3). Pts with 0, 1 or 2 of these factors had a 2 year progression rate of 0%, 48% and >75% respectively (p<0.01). Other prognostic parameters such as ZAP-70 and CD38 did not have independent prognostic utility. <<<RESPONSE TO THERAPY>>> 41 pts from MDACC were assessable for response to first therapy. Overall (OR) and complete response (CR) rates were: rituximab without chemotherapy (n=6), OR 67% CR 17%; purine analogue + rituximab combinations (n=20), OR 75% CR 30%; purine analogue, rituximab + alemtuzumab combinations (n=13), OR 85% CR 54%. The pt who achieved CR after rituximab was negative for minimal residual disease assessed by flow cytometry and consensus primer IgH PCR, and has remained in remission at 29 months. At 2 years, 75% of complete responders remained relapse free. <<<SURVIVAL FROM 17P- DIAGNOSIS>>> Two year survival was 78%. Independent predictors of inferior survival were age 60+ (HR 3.4), B-symptoms (HR 3.7) and 17p- in nuclei 70+% (HR 6.0). Considering age 60+ and 17p- in nuclei 70+% in a prognostic model, 2 year survival was 100%, 82% and 55% for pts with 0, 1 and 2 risk factors respectively. Other prognostic parameters such as ZAP-70, IgVH mutation status and CD38 did not have independent prognostic utility. <<<CONCLUSIONS>>> Pts with de novo 17p- CLL exhibit marked clinical heterogeneity, with some pts experiencing an indolent course with prolonged survival. Survival and time to treatment among patients with 17p- can be predicted using clinical and biological characteristics.