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In chronic lymphocytic leukemia (CLL), TP53 gene aberrations due to chromosome 17p deletion ⌊del (17p)⌋ and/or TP53 gene mutation are associated with adverse prognosis and poor response to chemo (immuno) therapeutic regimens. Deletion and/or mutation of the TP53 gene occur on average in 10-15% of untreated CLL patients, and the incidence rises to 40-50% in fludarabine-refractory cases. It has been shown that TP53 mutations in the absence of del (17p) occur in a sizeable proportion of CLL patients (~5% in first line treatment situation) and are also associated with significantly worse outcome.

The European Research Initiative on CLL (ERIC) has a longstanding interest in the standardization and harmonization of diagnostic techniques for such aberrations including FISH ⌊to detect del (17p)⌋ and molecular (to detect TP53 mutations) analyses, providing guidelines to the international scientific community (Pospisilova et al, Leukemia 2012).

Until recently, no effective treatments were available for these patients, as chemo (immuno) therapeutic regimens could only achieve limited and short-lasting responses (e.g. PFS approx. 12 months with FCR in the 1st line setting) with a dismal prognosis despite additional lines of treatments, with the allogeneic transplant being the only potentially curative approach.

Recently, however, the outcome of CLL patients with del (17p) and/or TP53 gene mutation has improved dramatically by treatment with novel, non-chemotherapeutic agents such as the signaling inhibitors ibrutinib and idelalisib (the latter in combination with Rituximab) and the BCL-2 inhibitor venetoclax, which have been approved by the FDA and the EMA for this group of patients. That said, long term follow-up is required before drawing definitive conclusions regarding the extent to which TP53 gene disruption may maintain a prognostic role also with these novel agents.

Availability of these new drugs creates the need for practicing hematologists to carefully screen for del (17p) and TP53 gene mutations in all cases before the implementation of both first and subsequent lines of treatment in order to select the most appropriate treatment, while avoiding potentially ineffective regimens and unnecessary toxicity. This is especially timely given that the appropriate diagnostic techniques are currently not available or utilized in all centers treating CLL patients; furthermore, with few exceptions, quality control procedures are not in place.