Waldenstrom’s: Peter’s promising clinical trial results
When Victorian vet Peter Younis relapsed four years ago, he opted to go on a clinical trial for a targeted therapy rather than having another course of chemotherapy.
The trial is for the experimental drug BGB-3111, which is effectively managing Peter’s rare form of lymphoma, called Waldenström’s Macroglobulinaemia (WM). It involves taking four capsules a day, and every two months he makes a day-long round trip from Port Campbell, where he lives in south west Victoria, to Melbourne for tests.
From Peter’s point of view, the trial “is just great”.
“I’ve had an excellent result – I’m alive, happy and have no side-effects.
“A big advantage is that I can just continue with my normal life. It’s unbelievably simple and non-disruptive for someone who has an active life,” explained Peter, a large animals vet who works mainly with cattle.
“This was such a better way of having treatment than sitting in a chemo chair for a day and going through the sickness afterwards.”
Peter’s diagnosis with WM 13 years ago was an incidental finding when he had blood tests following kidney stone treatment. The results showed a very high level of protein. Further investigations revealed high paraprotein and a bone marrow biopsy found he had WM.
“I wasn’t quite 50, which is young for this type of lymphoma,” said Peter, now 63.
He consulted a haematologist at Warnambool, went on ‘watch and wait’ and the following year his paraprotein level indicated the need to be treated. At the time, fatigue and muscle weakness were his main symptoms.
Peter had a course of traditional chemotherapy, which suppressed his WM significantly, and he was monitored over the next nine years until 2013 when the lymphoma started to return.
After a discussion with his haematologist he considered his two options, and being a scientist, Peter methodically drew up a list of the pros and cons of having more chemo versus a randomised controlled clinical trial*.
That he could end up in the control group was the major con with the trial, and the con for another course of chemo – the ‘sledgehammer approach’ – was that it “stuffs up your life for a while”.
“I’d be buggered for a few days and it was a week before I could get back to work. I enjoy my work,” he said.
A major pro for Peter regarding a trial was its “contribution to the greater scientific good”.
When he went to Melbourne to find out more, he was told about another trial – a Phase I study into the effects of dose escalation of the BTK inhibitor, BGB-3111.
It hadn’t been used in humans so the trial was a dose response study to determine where the levels lay between toxic and effective doses of BGB-3111. Participants were allocated to one of three dosage groups – 80mg, 160 or 320mg per day.
Peter started the trial in November 2014 on 80mg a day and spent the first couple of days at the Peter MacCallum Cancer Centre being closely monitored.
After 12 months on the trial, and having had a positive response to the drug, as measured by the paraprotein levels in his blood, Peter’s daily dose of BGB-3111 was increased to 160g, which resulted in a further drop in his paraprotein.
Several months later, ethics approval was granted for the trial protocol to change to twice daily dosing. Peter’s dose has since been increased, to 160mg twice a day, which is expected to be even more efficacious.
According to the principal investigator of the BGB-3111 trial, Dr Constantine Tam: “We are all very pleased with Peter’s response – his paraprotein started at 33g/L, and is now down to 3g/L, and continuing to fall.
“He has been on the drug for nearly two years now with no substantial side-effects. It is responses like these that gives us encouragement to proceed with larger studies,” said Dr Tam.
Peter said BGB-3111 was controlling, not curing, the WM.
“There is no suggestion this is a cure, because of the indolent nature of WM,” said Peter.
“Part of the deal with this trial is that I’ll have access to the drug for as long as is appropriate.”
He said the only downside to the treatment was having to fast for two hours before and one hour after taking the capsules, and not eating grapefruit which may interact with the drug.
Just as the farmers Peter works for trust in his knowledge and experience, he has faith in the expertise of his medical team.
“I work hard at being up-to-date with scientific literature in my job and I was surprised at how much I basically said to my haematologist – “you’re the expert” – and how little I’ve felt the need to hit the internet.
“He discussed my options in a manner that showed he had the same approach and I was satisfied with his explanations and logic.
“I’ve read as much as I can about Waldenström’s, but not incessantly. I really do trust my doctors and the Australian medical system.
“I work in developing countries – Sudan and Pakistan – which gives you an appreciation for how incredibly fortunate we are here to be able to take part in a study and contribute to medical research.”
* A study design that randomly assigns participants into an experimental group or a control group. As the study is conducted, the only expected difference between the control and experimental groups in a randomised controlled trial (RCT) is the outcome variable being studied.Posted on January 8th, 2018