iwCLL 2017 | Clinical approach to the diagnosis and initial evaluation of a CLL patient 

Session four at iwCLL 2017 took place on 14^th May 2017, and was titled “Strategies for the Evaluation and Treatment of CLL in the Front-line Setting.” The session was jointly chaired by Stephen Mulligan (University of Sydney, Royal North Shore Hospital) and Neil E. Kay (Mayo Clinic).

The first of two talks in this session was given by Davide Rossi, MD, from the Institute of Oncology Research and Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. His talk was titled “Clinical Approach to the Diagnosis and Initial Evaluation of a CLL Patient.”

CLL is split into three subgroups: clinically suspected, symptomatic, and asymptomatic. It is a genetically heterogeneous disease and lacks disease defining genetic lesions.

According to the WHO 2016 classification of Richter syndrome, clinical suspicions of transformation include:

• Asymmetric growth of localized lymph nodes
• Bulky disease
• B symptoms
• Sudden and excessive rise in levels of LDH

In terms of PET/CT in Richter syndrome diagnosis:

Clinical stage and iwCLL criteria assessment will determine if the disease in asymptomatic or symptomatic. Those with asymptomatic disease should be considered for patient counseling, the frequency of follow-up should be carefully evaluated, and patients should be identified for early intervention trials. For symptomatic patients, the most appropriate therapy should be selected. 

Abnormalities in TP53 are common in CLL, with their frequency increasing through MBL, early stage CLL, CLL requiring treatment, refractory CLL, and Richter transformation. Of TP53 abnormalities, 10% are deletion only, 20% are mutation only, and 70% are mutation and deletion.

The survival outcomes of R/R patients by chromosomal abnormality identified by FISH after treatment with ibrutinib have been previously reported (O’Brien et al. ASH 2016):

Molecular mechanisms of resistance to ibrutinib include:

• BTK C481S mutation
• PLCG2 mutation (several; gain of function)
• Absent in ibrutinib naïve CLL
• Most of CLL showing acquired resistance
• Enriched in CLL with 17p deletion

The survival outcomes in R/R patients by IGHV mutational status treated with ibrutinib have also been reported (O’Brien et al. ASH 2016):

CLL prognostic markers: