Blood cancers

Improvement in sequencing CLL provides prognostic indicator

Next generation sequencing has significantly improved definition of the immunoglobulin heavy chain variable region (IGHV) in patients with chronic lymphocytic leukaemia.

Associate Professor Bryone Kuss, academic head of molecular medicine and pathology at Flinders Medical Centre and Flinders University, said that with next generation sequencing less than 2% of patients’ IGHV status remained undetermined.

“With the previous technology, it had sometimes been difficult to define the IGHV sequence and we were finding we were not getting a clear answer in up to 30% of patients,” she said.

Speaking after the recent CLL ARC Forum in Sydney, Associate Professor Kuss told the limbic there was a clear prognostic impact from the test.

Patients with the hyper-mutations responded well to fludarabine, cyclophosphamide, rituximab (FCR) chemotherapy with a 10-year survival of about 60%.

“It is very clear that the patients with IGHV that is un-mutated have a poorer prognosis, progress more quickly and don’t respond as well as the hyper-mutated group.”

She said these patients might get two to three years remission with six cycles of FCR but would ultimately relapse.

Given the lack of other treatment options, she said the implications of an adverse IGHV status might influence decisions about referral to clinical trials.

Associate Professor Kuss said the technology was now well validated but only available at a few laboratories worldwide, including Flinders Medical Centre.

She said while some hospitals were prepared to fund the test, the cost of about $500 was one of the barriers to its wider use.

“Private patients may also be prepared to pay for a better understanding around their choices, especially in younger patients with progressive CLL who want to make the right long-term choices.”

“There is a long history of molecular testing not being reimbursed. It is always way behind the therapies although the results can change management of these patients.”

“The RACP has been working to get this addressed and a position paper re: reimbursement of molecular tests has been submitted to government.”

Professor Kuss added that whole karyotype analysis had demonstrated there was more genetic complexity in CLL than was previously understood via fluorescence in situ hybridization (FISH) technology.

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