We are talking about the topic of mantle cell lymphoma which is a rare form of non-Hodgkin’s lymphoma, about 6%, but in the US each year there are about 4,000 people diagnosed. Because we are able to prolong people’s lives so the prevalence is much more than 4,000 people, it’s much higher. So for people who don’t know mantle cell lymphoma it may be a rare topic but for the patients and families who are affected by this dangerous disease, life-threatening disease, it’s a huge deal.
When the patients are young, when they’re diagnosed with mantle cell lymphoma, we are able to give them intensive chemotherapies. Their survival is over ten years on the chemo-intensive therapies. However, in elderly people, especially when they are aged over 65, they are not able to tolerate intensive chemotherapy like the young people do so their survival is only about five years. So there’s a big discrepancy between people less than 65 or older than 65. So in order to close this gap we did the SHINE clinical trial. The standard therapy for this population, for the elderly population with newly diagnosed mantle cell lymphoma, are usually treated with bendamustine rituximab. This has a failure free survival of, at the best, 3.5 years. So their overall survival is about five years.
In this clinical trial we did a phase III clinical trial. One arm is the ibrutinib with the standard bendamustine rituximab, we called it BR. So ibrutinib with BR. On the other arm is placebo plus BR so we are able to see the difference that ibrutinib could make in this population. So it’s an international study, gigantic international study, including 183 of the world’s best hospitals in 28 countries; almost on every continent there are patients enrolled on this study. The study was designed ten years ago and I had the fortune to lead the scientific steering committee who designed the study with many colleagues in Europe and in America. So we started enrolment in the trial about ten years ago, actually about three years later. So we enrolled 523 patients, two arms.
The endpoint for the study is progression free survival. So from the start of the therapy until thepatient has progression or died from something, that’s the time we’re talking about. This is a consensus defined endpoint approved by the FDA and all the regulatory agencies – EMA and all – all recognised PFS. Why? Because if we do overall survival, which is the gold standard, in this clinical trial it would take 1,000-2,000 patients over 15-20 years and our patients cannot wait that long. So we used a surrogate marker of progression free survival.
In this progression free survival the study is a huge outstanding success; it’s very significant. With the ibrutinib arm, the experimental arm, the PFS was 6.7 years and with the placebo arm the median PFS was 4.4 years. So there’s a 2.3 year gain over the control arm. This gain is very meaningful to our patients. So suppose we have a patient who is 71 years old, they come to my clinic to see Dr Wang – ‘I want to get therapy from you.’ I say, ‘Okay, we’ll give you the therapy.’ If I give them ibrutinib and BR they have 6.7 years, they don’t need any other therapy and they probably will go on to live over ten years, when their age is 81.
So, in my opinion, I’ve been treating mantle cell lymphoma for twenty years and in my opinion the first therapy is the most important therapy for mantle cell lymphoma. Why? Because at that time the patients’ resources are still intact. Whatever therapy you give them the response is going to be higher and the duration will last longer and they are able to tolerate the side effects much better than later. So you give them the first therapy, you hope the duration lasts as long as possible. Ten years later we’ll figure something else out for this patient.
So this is a very positive study; in my opinion it’s going to change the current standard of care and it’s really great news for our patients and families. I want to thank all the patients and their families, their determination, their bravery and their hard work. It made this trial all possible.
We looked at also the toxicities and obviously the toxicities occurred more in the experimental arm with ibrutinib, less in the placebo arm. For example, rash and pneumonia happens 10% higher in the ibrutinib arm than the placebo arm. But when we designed the study ten years ago we were at the start of using BTK inhibitors. After ten years we have evolved, we know exactly how to handle the side effects so we are much more comfortable and more effective in handling the side effects. Also the other side effects like anaemia and also the diarrhoea occurs a little more in the ibrutinib arm than in the placebo arm, we know how to handle those side effects.
We also looked at the overall response rate. The overall response rate is about 90% in each arm. The complete response rate is 65% in the ibrutinib arm versus only 57% in the placebo arm. So the CR rate is much higher than the placebo arm.