It won’t happen overnight… but response to ibrutinib better in treatment naïve


By Mardi Chapman

2 Mar 2018

While not available in Australia as a first line treatment for chronic lymphocytic leukaemia (CLL) or small lymphocytic leukaemia (SLL), ibrutinib has been shown to be more effective in achieving complete response when given before other treatments.

The study, which pooled data from trials PCYC-1102 and PCYC-1112, found the odds of achieving complete response were increased for patients with no previous treatment compared to one or more other treatments (OR 2.65).

The other significant predictor of complete response was lack of bulky disease – defined as lymph node ≥5cm (OR 4.97).

The overall response rate for the 327 patients was a sustained 89.6% from 21 months. Complete response was achieved more slowly in about 10% of patients.

Beta2-microglobulin levels (≤3.5 v >3.5mg/L) were predictive of complete response in the univariate analysis but not in the multivariate analysis.

Other baseline patient characteristics such as ECOG performance, del11q, del17p and unmutated IGHV status were not associated with complete response rates.

The study authors said: ‘attainment of complete response has historically been associated with superior progression-free and overall survival’.

“The achievement of complete response with ibrutinib therapy at the time of this analysis allowed patients to remain in follow-up for a median of 26.4 months with no deaths or disease progression.”

They added the depth of response could be expected to improve further and ‘may offer an opportunity to explore concepts, such as discontinuation of ibrutinib therapy’.

However Associate Professor Constantine Tam, from Peter MacCallum Cancer Centre, told the limbic that cessation of therapy was highly unlikely.

“If you have a true complete response and you are MRD negative, you might be able to come off the drug but ibrutinib remissions are almost never MRD negative. So given the small rate of complete response, only a tiny proportion of those patients will be MRD negative and be able to stop the drug.”

He said the findings highlighted the long-term value of ibrutinib.

“Complete response doesn’t happen overnight. You don’t get complete response in the first few months; it’s uncommon to get it in the first year but as the patients go on for two, three or longer years, the proportion of complete response goes up.”

“So it takes time to mature and it suggests ibrutinib is a long-term drug – you need to take it long-term to get the best benefit from it.”

Associate Professor Tam said the fact treatment naïve patients did better in terms of complete response was an interesting observation but of little value.

“In Australia nothing is going to change because we can’t get ibrutinib front line anyway but I guess this a suggestion that if you have a number of different choices – second, third and fourth line treatments – you might want to prioritise ibrutinib in earlier line treatment and before they have really bulky disease.”

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