ABT-199 trial gives Wolfe new lease on life
Wolfe Rakusin says he’s very lucky. He was in the right place at the right time to have access to the new CLL drug, ABT-199, and he describes his response to the new compound as “outstanding”.
“It’s given me a new lease of life,” said Wolfe, 76, of Melbourne, who has only just retired as an ophthalmologist, having worked since 1966.
ABT-199, discovered by an Australian team of Melbourne-based researchers, shows great promise for people with the most common form of leukaemia – chronic lymphocytic leukaemia.
In a world-first Phase I trial*, preliminary findings announced late last year found those with CLL who had an extremely poor prognosis achieved an 84% response rate and the bone marrow cancer was cleared in 23% of trial participants.
Wolfe went on the Phase IB trial last September. The regimen for this trial is ABT-199 in tablet form combined with rituximab.
In July 2007, Wolfe was diagnosed with an aggressive form of CLL while holidaying in the U.S.
Before the diagnosis was made he’d felt tired and listless, was breathless and bruised easily. He also had night sweats and noticed the glands in his neck were up.
“I’d had a heart bypass in 1994 and thought it was a problem with my heart,” explained Wolfe.
In the U.S. he had a pleural tap to treat fluid on the lung and when a blood test showed he had leukaemia, he cut short his travels and returned to Australia.
“My lymphocyte count at the time was 150,000 and I needed to start treatment immediately,” said Wolfe.
Over five months he had a combination of fludarabine, cyclophosphamide and rituximab, and after recovering, continued life as normal, working, playing golf, spending time with his family and travelling.
He saw his haematologist every four months and was in remission for four years until the end of 2011 when his lymphocyte count started to increase.
In February 2012 he began a second course of chemo – the same combination as previously, plus vincristine. He was in remission for one year before his lymphocyte count began rising again. He’d become refractory (no longer responded) to conventional treatment for CLL.
“My haematologist was thinking of other forms of treatment.
He called a colleague who saw me the same day, and who explained details of the ABT-199 trial. However, there was a waiting list so I couldn’t be accepted on to the trial immediately,” Wolf explained.
But two weeks later, a spot became available and he had extensive tests to see if he was a suitable candidate.
“I was considered a very high risk patient. They were worried about my kidney function and ability to withstand the treatment, primarily because I had developed tumour lysis syndrome during my first course of chemotherapy when my lymphocyte count was extremely high,” Wolfe explained. (Tumour lysis syndrome, or TLS, is a problem that can occur because of a rapid breakdown of cancer cells when chemotherapy is given. It may occur at the start of treatment when a large number of tumour cells are destroyed, deposited in the blood stream and overwhelm the kidneys and liver.)
“The lymphocyte breakdown products had overloaded my kidneys, but with treatment, I recovered and continued with chemo.
“If you get rapid breakdown of the lymphocytes during treatment, it creates a lot of toxic substances that can overload the kidneys and produce kidney failure.
“In the first trial there were two deaths in the U.S. and they had to suspend the trial to find out the reason. Because the dose was escalated too quickly, it resulted in a too rapid breakdown of the cells.”
After being given intravenous fluids to boost his kidney function, Wolfe was accepted on to the trial.
“In the Phase IB trial, they’ve added rituximab to the ABT-199 to determine whether this combination gives a deeper and longer lasting remission, or even a cure.”
Wolfe was admitted to hospital and put on a slowly escalating dose.
“They worked out the optimal dose for me based on my height and weight, which was 500mg a day (five tablets). They started me on 20mg a day for a week, then 50mg for a week, then 100mg for a week, then 200mg for a week, then 500mg.
“I was admitted for three days for each escalation and given intravenous fluids to maintain my hydration and they carefully monitored me and took bloods every two hours.
“That was a bit frustrating but the drug company has very strict protocols to ensure the safety of patients on the trial, and they (the trial team) and the staff at Peter Mac were very caring, efficient, and careful, being very aware of the previous deaths.
“After a month, I started rituximab, given intravenously, and I’m still on that,” said Wolfe, who’d had four of his six scheduled treatments of rituximab when interviewed by CLL News.
“The doctors are amazed at my progress and I’ve had no side-effects.
In September my blood count was 90,000 and now it’s normal at less than 4000. I anticipate I’ll be on ABT-199 forever.
“I think this (ABT-199) is a wonderful trial. It is an amazing drug, which does not work like conventional chemo, and the sooner it gets on the PBS the better, rather than waiting another five or six years. It should be available to everybody who is refractory.
“It has made me feel 20 years younger. I feel great. I’m stronger, my energy levels are better than before (CLL) and I’m playing better golf than before.
“I really can’t complain at all. I went back to work one day a week but have since retired as I have other things to do. My wife, Fay, and I have been married 52 years, our children are all over the world and we have nine grandchildren who we travel to visit.”
* An Australian research team discovered how to ‘switch off’ cancer cells. Some of the early laboratory development of the therapy was funded through the Leukaemia Foundation’s National Research Program in 2012.
From CLL News including SLL published in March 2014