Inhibitors slow MF

• Diagnosed at age 12
• PV treatment quest
• Surviving a transplant
• Keeping the faith with ET
• Two decades with PV
• Cyclist grapples with PV
• Stroke hit at age 36
• First symptom foot pain
• Survivorship after BMT
• Diagnosed while pregnant
• PV diagnosed age 17
• PV leads to stroke
• Inhibitors slow MF
• Medication pros, cons

Alisia O’Sullivan spoke with Max Smith about his voyage through MF and what he sees next for research. Editor’s note: JAK2 inhibitor trials are now open in the UK and Europe for people with myelofibrosis.

When I spoke with Max recently, I was immediately impressed with his positive attitude. He is a man committed to surviving, and whose steady approach to research and planning may well have extended his life over many years in the face of a complex and difficult illness.

Initial diagnosis

When Max’s myelofibrosis was first diagnosed, he was given limited information – in fact, his doctors did not alert him at that time to the potential seriousness of his condition. It was only a decade later in 1996 when Max began suffering from the typical symptoms of myelofibrosis – fatigue, dizziness and an enlarged spleen – that his doctors shared the full implications of the disorder with him. They gave him a prognosis of shortened life expectancy with only a few remaining years to live. When he first heard this devastating news, Max sharpened his plan of attack for managing his condition, an approach he describes as “full-on proactive.”

The hunt for trials

Beginning in 1996, Max undertook a world- wide investigation into drug trials available for myelofibrosis. He put himself forward for research trials at the Mayo Clinic in the United States, making the decision to fund several medical investigations out of his own pocket. In 1997, Max was assessed at the Mayo Clinic (US) in preparation for enrollment in the medical centre’s myelofibrosis drug trials. Since that time Max has taken part in a total of seven research trials. Although he is enrolled in trials in the US, he has continued to work closely with his local haematologist as well, with two goals in mind: to extend his life expectancy and to improve his quality of life.

“I understand that the NHS in the UK is not in a position to assist in experimental trials overseas,” Max explains. “I am fortunate in that I have been fi- nancially secure enough to fund this care personally.” Max has incurred many costs including flights back and forth to the US and hotel accommodation while he undergoes medical assessments prior to, during and post-trial – costs that have quickly mounted and are on-going. Max also made the financial commitment to self-fund the medical tests that he requires every twelve weeks, including bone marrow biopsies (BMBs), full blood counts, electrocardiograms (EKGs) and more. Editor’s note: JAK2 inhibitor trials are now open in the UK and Europe and available under the NHS for patients who meet the trial criteria.

NHS collaboration

Max’s haematologist in the UK has been his consultant and mentor for the last thirteen years, and although he was initially unsure about the benefits of Max’s participation in US-based research, he has subsequently proven very supportive, even encouraged by some of the research and the results. Max speaks highly of the way in which shared-care support between his UK haematologist and the Mayo Clinic has worked in his case. He stresses that, “Support from my NHS hospital in the UK and my consultant has been wonderful.”

In November 2007 Max enrolled in Phase 1 of the JAK-2 inhibitor trials at the Mayo Clinic in Rochester, Minnesota. The goal in the first phase of any drug trial is to ensure the drug is safe and to check the effectiveness of the drug, initially in a very small group of patients. A group of about twenty patients were enrolled in Phase 1 of the Mayo Clinic’s JAK2 inhibitor trial, including Max.

Extensive testing

At the start of the study, Max underwent an extensive physical examination involving an electrocardiogram, a bone marrow biopsy and blood work analysis. He was then given approval to enter the trial and he began taking the full dose of the JAK-2 inhibitor drug, an oral drug taken twice a day. Max’s responses to the drug were and continue to be monitored on a twelve-week cycle in Minnesota. Max also makes a fortnightly visit to his haematology department in the UK for a full blood chemistry check, results of which are forwarded to the US.

The trial expands

The Mayo Clinic’s inhibitor drug has initially proven safe and has shown signs of effectiveness. The trial has thus moved into Phase 2 allowing more patients to enrol.

Max was able to continue into Phase 2 of the study, and he remains committed to frequent visits to Minnesota for continued testing. He explains that he is in a unique position: “As far as I’m aware I’m the only patient to remain on the maximum daily dose of the drug. The other patients in the trial are now now taking a lower daily dose.”

Excellent results

“Out of all of the trials I’ve undertaken, this is the first time that I have ever reached Phase 2 of a trial,” says Max. And so far, this trial has provided the most satisfactory results and relief for his symptoms. Max recalls, “I did suffer some minor stomach upset and disorientation in the early days, but these problems have now passed. Since I began taking the drug my spleen has much reduced and my haemoglobin, white cell counts and platelets levels have all stabilised to within almost normal range,” he says, and all this without any current discernible side effects.

Max feels that the drug is helping to slow the progress of his disease. He also believes that the experimental medicines he took during previous trials – drugs geared to slowing down the progress of MF – must have played some part in extending his life expectancy beyond the original two to fifteen years predicted at the outset of his disease in 1985. However, Max is keen to stress that because he is probably the only patient to remain on the high dose JAK-2 inhibitor he is obviously an atypical patient. He knows that the results for other participants in the trial have been mixed, although he also adds that he is not aware of any patients in whom there has been a seriously adverse consequence. The only non-beneficial outcome has been that in some cases the drug has not relieved existing symptoms of MF.

Uncertain future

With only one month to go before the end of Year 2 of the study, Max explains that “the overall feedback on the drug appears to show mixed results. This creates a certain level of uncertainty and anxiety about what may happen next, especially for me as I myself have responded so well to the drug.” At this moment Max does not know if the study will continue. And even if it does, there is no guarantee that he will be allowed to continue in the trials.

Max is quite phlegmatic about the risks involved in any research trial and the uncertainty of the outcomes, but he does express some concerns. “If the trial did not continue it would be a great disappointment to me personally. I hope and believe that at some point there will be a cure for this disease. I have an on-going commitment to be part of this quest in whatever way possible.”

Author’s note: Having interviewed Max, I would like to add a postscript and offer a big thank you to Max for being willing to share his experience of this particular trial, but also for his obvious willingness to take a risk as a ‘research guinea-pig’ . Without people like Max as a fellow MPD sufferer I believe we would be a long way from finding any new drugs. Therefore I do hope that Max will continue to be allowed access to a drug that appears to work, as well as enjoying many many more active and happy years with his wife, children, grandchildren and great-grandchildren.