MMI Patient & Family Day Report 2019:Living longer with multiple myeloma

Danielle Barron Reports
At the heart of every Multiple Myeloma Patient and Family Information day is the lived experience of those that have been diagnosed with multiple myeloma, and those who love them. In what was an emotional presentation, Tipperary couple John and Charlotte Crowe outlined how their lives had changed dramatically since John’s multiple myeloma journey began. John, a part-time farmer and office worker, had been suffering from severe bone pain and was eventually diagnosed with multiple myeloma in 2007. He has undergone a range of treatments for his multiple myeloma, as well as having a hip replacement and a stent fitted.

John explained how he found the chemotherapy and subsequent autologous stem cell transplant very difficult, and he also discussed the psychological impact of his illness. “I made a conscious decision to fight this cancer with all my being… to the extent that I built a virtual wall around myself.” Despite feeling tired a lot of the time, he said he now feels good considering he can do a full day’s work on his farm. “I am obviously very disappointed I have multiple myeloma, but I am very happy with the treatment and care I have received til now, and I feel privileged I have survived this long.”

He told the audience that his wife had been by his side through it all, and they both praised the medical teams in University Hospital Limerick and St James’s Hospital Dublin that had cared for John. Charlotte spoke about John’s illness from the carer and spouse’s perspective; an emotionally difficult time, it was also practically difficult, as she recalled having to learn how to milk cows for the first time while John recovered. Learning the names of each medication and working out a timetable for when they should be taken was a major challenge, she admitted.

“While John was sick someone had to deal with the day to day business of the farm and our family – all the things your head won’t allow you to think about but can’t because your heart is broken.”

Professor Paul Browne, consultant in haematology at St James’s Hospital, was involved in John’s treatment. He followed John and Charlotte with a medical overview of myeloma, in his presentation entitled “Understanding Myeloma”.

Prof Browne began by explaining that the fundamental problem in myeloma is abnormal plasma cells proliferating in the bone marrow, which lead to tumours in the bones. Its cause remains unclear, and there are many theories for why this happens, he admitted. Various suggestions are that it may be due to radiation, environmental factors, immune system stimulation, or genetic factors, but these are largely unproven and research is still ongoing, he said.
Multiple myeloma may be rare compared with other cancers, but there are more than 2,000 people living with myeloma in Ireland today. It is typically diagnosed after the age of 65, and seems to impact men slightly more than women.

Once the diagnosis is made, the first question is always “is treatment necessary?”; the majority of patients will require some form of treatment, as they will have symptoms such as anaemia, bone pain/lytic lesions, kidney failure, and/or high calcium, explained Prof Browne. “But there is a balance that has to be achieved between killing myeloma cells, and treating symptoms,” he added. Patients

with asymptomatic or “smouldering” myeloma will instead usually require careful monitoring, although this position is evolving, he noted.

A complex condition, historically treatment options were limited and crude, but recent medical advances have completely transformed how multiple myeloma is managed, continued Prof Browne. While simple measures include drinking plenty of fluids in order to protect the kidneys, keeping mobile to maintain bone health, and antibiotics for prompt treatment of infection, there are a plethora of established and newer medical treatments employed in multiple myeloma nowadays, he explained.

Factors affecting the choice of treatment include the disease pattern and type, thrombosis risk, presence of neuropathy, and low blood counts. Autologous stem cell transplant, while an older and difficult treatment, still remains highly effective, doubling a patient’s chances of achieving remission, he confirmed.

The concept of “minimal residual disease” was discussed by the professor, and he explained how maintenance treatment with therapies such as lenalidomide following transplant can help achieve this. He also discussed how stem cell transplants are typically not carried out in older patients, but he qualified this by saying if they are fit and well it may still be an option. Novel immunotherapies are proving to be a gamechanger in this cohort of patients, however. “The evidence shows that people in their seventies do incredibly well with new treatments,” he said. “There are many people living extremely well with myeloma because of these new treatments and they are fit and well into
their eighties.”

Many heads could be seen nodding in agreement during the next presentation, as psycho-oncologist Eugene Beirne from St James’s Hospital spoke about the psychological aspects of living with myeloma.

Beirne began by saying there can be multiple responses to the chronic running and remitting trajectory of a myeloma diagnosis. Common responses include distress/shock, disbelief, mortality, anger, guilt, worry, and/or sadness. “It’s like a grief reaction, and everyone goes through it,” he advised.

Beirne stressed that support can be accessed from a wide variety of sources, including the treating team, GP, Daffodil Centres, Arc, etc., as well as psycho oncology services, which are finally on the increase. “Between one quarter and one-third of all people with any cancer diagnosis will experience these symptoms to a distressing enough degree to warrant formal assessment by somebody like myself,” he told the audience.

In terms of intervention, transient distress may simply require family support, while persistent mild distress may require additional support from their GP or the clinical nurse specialist. Severe distress or psychosis will require more intensive and structured psychological or psychiatric intervention.
Beirne warned that this “shouldn’t be easy”. “It should be very difficult – if it’s easy you aren’t working hard enough and what you put in is what you will get out.” He also stressed the importance of psycho-oncology as an essential pillar of treatment, saying it is as important as any other medical appointment.

“Everything in moderation, including moderation. You need some anxiety and stress in your life – having none at all isn’t a good thing,” concluded Beirne.

Liz Higgins, Autologous Transplant Co-Ordinator at St James’s Hospital, then gave a practical, step- by-step guide to what’s involved in a stem cell transplant for patients with multiple myeloma.
A peripheral blood stem cell transplant (PBSCT) is carried out in order to facilitate high dose therapy in some malignant conditions, including multiple myeloma, explained Ms Higgins. She outlined the procedure: an individual’s bone marrow stem cells are first eliminated, high dose chemotherapy is given and stem cell “rescue” then takes place with a previously harvested portion of the individual’s own bone marrow or peripheral blood stem cells.

In Ireland, these transplants are carried out at University Hospital Galway, St Vincent’s University Hospital and St James’s Hospital. “The numbers of transplants are gradually increasing every year but on average we do about 50-60 transplants in St James’s every year,” explains Ms Higgins. Following referral, a patient will receive an appointment with the dedicated transplant counselling clinic. “Our consultants will see no more than three patients in each clinic as they want to spend adequate time with each patient to explain all the information they will be giving them.”
A patient will first attend to have their stem cells harvested, and will be admitted approximately 6-8 weeks later for their transplant. During this time, the major side effects for patients include mucositis, which involves a sore mouth and gut. Low blood counts are also an issue, meaning infection risk is high. “They will fall to pretty dangerous levels and you are extremely susceptible to infection.” Fatigue is also a huge problem, and can be “overwhelming”, she added.

Indeed, cancer-related fatigue (CRF) was the focus of the next presentation. Its impact and management were outlined by nursing lecturer at University College Cork, Dr Patricia O’Regan, who told attendees that there is “no magic pill” for its treatment. “Cancer-related fatigue is very different to that experienced by normal healthy people.”

She explained that CRF remains an under-recognised and under-discussed condition, despite its deleterious impact on patient quality of life. “Fatigue is the most debilitating, yet least understood and addressed side effect of cancer treatment.”

According to Dr O’Regan, CRF is multifactorial, subjective and rarely isolated, mostly occurring in “symptom clusters” of pain, distress, anaemia, and sleep disturbance. The main symptoms are a lack of energy, shortness of breath, sleepiness, and tiredness even after sleeping, but it can manifest in a multitude of ways, she said. “It is variable in severity with physical, emotional, mental, functional and spiritual components.”

Treatments such as surgery, radiotherapy, chemo and biological therapies will cause fatigue in almost all cancer patients, and all should be assessed for it, noted Dr O’Regan. She explained that in multiple myeloma patients treated with cytotoxic agents, proteasome inhibitors (PIs), and immunomodulatory drugs (IMiDs) such as bortezomib, lenalidomide, and thalidomide, CRF is a common adverse event.

While there are effective pharmacological treatments, in terms of non-pharmacological treatments, exercise has the most supporting evidence when it comes to effectiveness, while psychosocial interventions such as CBT have also been found to be beneficial. “While CRF is debilitating and a potentially severe symptom, it does improve in time, and many people return to their normal level of functioning,” she assured the audience.

Dr Jess Walsh, Clinical Trials Coordinator at Blood Cancer Network Ireland (BCNI) was on hand next to describe a number of current and upcoming clinical trials in Ireland for multiple myeloma patients. The BCNI clinical trials network operates in five clinical sites across Ireland, enabling equal access for all Irish patients, she explained.

“Early phase clinical trials give patients access to novel drugs and therapies that would not be available otherwise,” she noted.

One current BCNI-mediated clinical trial is CyBorD-DARA (Cyclophosphamide, Bortezomib, Dexamethasone, Daratumumab), which is investigating the standard of care plus the addition of the monoclonal antibody daratumumab in the upfront treatment of newly diagnosed multiple myeloma. It is now closed to recruitment, but patients remain on monthly maintenance treatment, she explained.

Upcoming trials include the CPD-DARA trial, a small investigator-initiated study looking at a combination of cyclophosphamide, pomalidomide, dexamethasone and daratumumab; this trial will involve a limited number of patients with relapsed/refractory multiple myeloma who have been on at least three lines of previous therapy. A much larger randomised controlled trial, EMN-18, is a European-wide study into the upfront treatment of newly-diagnosed multiple myeloma using the CyBorD-DARA regime as one experimental arm.

Despite these examples, Ireland doesn’t have as many cancer trials as we should, admitted Dr Walsh; reasons include poor awareness, lack of funding, and the failure to integrate clinical research into the healthcare system.

“The benefits of clinical research are not fully understood by general public,” she said. “Patient outcomes and these benefits need to be promoted.”

Capping off the day as always was a look at what the future might hold in multiple myeloma treatment. Consultant haematologist Dr John Quinn from Beaumont Hospital explained that the treatment pathway and regimens “continue to evolve”, and survival continues to improve. “New medications continue to be developed and are being made available to Irish patients,” he said, adding that these include the immunotherapies pomalidomide, daratumumab, carfilzomib, and ixazomib. For example, the addition of daratumumab to current treatment regimens is showing excellent promise in first-line treatment.

Yet the disease remains variable, and “one size does not fit all” – one treatment may suit a particular patient but not another, he cautioned. Relapsed myeloma also remains much more difficult to treat – while there are over 20 drugs and combinations available, it’s still unclear which is the best due to lack of data.

Targeted immunotherapies, such as bispecific T-cell engagers (BITE) and CAR-T cell therapy, are very much a hot topic in multiple myeloma, as well as many other cancers, Dr Quinn explained. These therapies are showing excellent response rates in patients who have begun to fail other therapies; however, these responses are not very durable and this is being worked on. “Clinical trials is the best way to access new medicines,” reiterated Dr Quinn.
And despite recent advances, the use of inappropriate language such as “cure” is unhelpful, Dr Quinn admitted. “Multiple myeloma will be more of a chronic disease than something that is curable, in the majority of cases,” he noted.