Multiple myeloma painful death

Shaji Kumar, MD

Associate Professor
Division of Hematology
Mayo Clinic
Rochester, Minnesota

H&O What are the survival outcomes following diagnosis of multiple myeloma?

SK Survival has clearly improved over the past decade. As of 10 years ago, the median survival of patients was 3–4 years. Today, it is approximately 8 years and improving. What is also clear is that survival is improving not only during the early part of the disease, but continuously throughout the disease course. In our experience at the Mayo Clinic, patients treated in the past 5 years seem to be doing better than the patients who were seen in the 5 years prior to that. However, approximately 25% of myeloma patients still die within the first 3 years of their disease, and approximately 10% of patients die within the first year. So, one area that still needs significant improvement is the number of patients who are dying within the first year following diagnosis.

H&O What are the treatment options in multiple myeloma, and which patients require specialized care?

SK There are many new drugs available, such as proteasome inhibitors and immunomodulatory drugs, which have decreased the proportion of patients who are dying within the first year of diagnosis. Numerous phase III trials, such as the Eastern Cooperative Oncology Group (ECOG) E1A00 trial, have examined these novel agents in combination with dexamethasone or as part of multidrug combinations for initial therapy. Some notable results have emerged from these studies. With the new regimens, early mortality rates have significantly decreased when 1 or more of these agents are used upfront. In addition, the use of lenalidomide (Revlimid, Celgene) or bortezomib (Velcade, Millennium Pharmaceuticals), or a combination of both along with dexamethasone, has resulted in very high response rates, including complete response rates previously unseen outside the context of transplant.

Increasingly, it has been recognized that dose reductions of many myeloma therapies may benefit elderly patients, in whom the delivery of standard-dose therapy is difficult. In the MM-009 and MM-010 trials, treatment-related toxicities that prompted dose reductions of lenalidomide (from a starting dose of 25 mg) were more common in elderly patients and in patients with renal impairment. Lower doses of lenalidomide are better tolerated in this patient group. Similarly, the use of lower-dose bortezomib (weekly as opposed to twice weekly) appears to produce fewer neurologic and nonhematologic toxicities without compromising efficacy. Dose reduction of corticosteroids is often warranted in elderly patients as well, in whom diabetes, mood disorders, and increased risk of infections are more common.

H&O How does a risk-adapted therapy strategy affect the treatment approach?

SK At the Mayo Clinic, newly diagnosed myeloma is stratified into standard-, intermediate-, and high-risk disease using the strategy known as mSMART (Mayo Stratification for Myeloma and Risk-adapted Therapy). It allows a risk-based approach to therapy, maximizing benefit, and, at the same time, helps to minimize the impact on the patient’s quality of life. Patients with standard-risk myeloma have a median overall survival (OS) of over 8 years, whereas those with high-risk disease have a median OS of 2–3 years. Treatment approaches differ for each risk group, as detailed in Figure 1. In addition, among patients who are older and in those with a poor performance status at diagnosis, we have to be careful about potential treatment-related side effects. It is important to modify drug doses accordingly and to remain alert for infections so they may be treated right away with antibiotics or antibiotic prophylaxis. Improvements in supportive care, especially the routine use of bisphosphonates, can reduce the incidence of bony complications, which often contribute to morbidity and, indirectly, to mortality.

H&O Can you discuss your recent study on predictive factors of early mortality in multiple myeloma?

SK We must fully understand which factors contribute to early death in multiple myeloma in order to address this problem. There have not been any previous systematic studies that have looked at this issue in a clear fashion. Our finding that 10% of the patients seen at the clinic tend to die in the first year is probably an underrepresentation; many newly diagnosed patients do not actually make it to a larger center like ours.

Our study was presented at the 2011 American Society of Hematology (ASH) meeting. We examined a cohort of patients who were seen over a 10-year period, from 1999–2008. We identified 265 patients who died within 12 months of diagnosis. For each of these patients, 2 controls were identified, each of whom had at least 12 months of follow-up, were alive at the time of last follow-up, and were closest to the deceased patient in terms of the timing of diagnosis.

Using the clinical and laboratory features, we identified parameters that best predicted for 12-month mortality. The factors that we found to be predictive of a poorer outcome within the first year included patient age greater than 72 years, International Staging System (ISS) stage III disease, Eastern Cooperative Oncology Group (ECOG) performance status greater than 2, and high levels of calcium at diagnosis. None of these factors were necessarily unexpected; the risk of death within the first year is largely driven by baseline health status and the severity of complications resulting from the disease or medications, as well as comorbidities like diabetes, high blood pressure, and poor renal function.

H&O Where should we focus our efforts for the future?

SK We must target this higher risk patient population for innovative approaches in order to improve outcome. The key is to conduct clinical trials focusing specifically on these patients, who are at risk for early death. All too often, these patients are left out of trials, and are thus not represented in treatment data. I think that the more we include these patients in clinical trials, the more we will learn about what the answers might be for treating this hidden population. Clinical trials could look at issues such as less frequent dosing, lower dosing, or therapies that are oral or subcutaneous rather than intravenous. We must discover and implement new methods that will allow these patients to minimize trips to the hospital and decrease their risk of complications.

Suggested Readings

Augustson BM, Begum G, Dunn JA, et al. Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United kingdom Medical Research Council trials between 1980 and 2002–Medical Research Council Adult Leukaemia Working Party. J Clin Oncol. 2005;23:9219-9226.

Rana V, Srivastava G, Hayman SR, et al. Factors predicting early mortality in patients with newly diagnosed multiple myeloma. Blood (ASH Annual Meeting Abstracts). 2011;118: Abstract 3981.

Rajkumar SV, Blood E, Vesole DH, Fonseca R, Greipp PR. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2006;24:431‐436.

Rajkumar SV, Jacobus S, Callander N, et al. Phase III trial of lenalidomide plus high‐dose dexamethasone versus lenalidomide plus low‐dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol (ASCO Annual Meeting Abstracts). 2007;25: Abstract LBA8025.

Dimopoulos MA, Spencer A, Attal M, et al. Study of lenalidomide plus dexamethasone versus dexamethasone alone in relapsed or refractory multiple myeloma (MM): results of a phase 3 study (MM-010). Blood (ASH Annual Meeting Abstracts). 2005;106: Abstract 6.

Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133-2142.

Chesi M, Bergsagel PL. Many multiple myelomas: making more of the molecular mayhem. Hematology Am Soc Hematol Educ Program. 2011;2011:344-353.

There a lots of things people would like to have more of: more candy, more friends, more money, and more hours in the day. America seems to run on the notion that more is inherently better – if not, best. Americans like to take a good thing and see it multiplied. However, there are some circumstances under which “more” isn’t really desired. Many kids might speak to the fact that one lima bean is enough. Multiple lima beans can be a horror to behold on the dinner plate! Sometimes the difficulty with “more” arrives in the form of personal limitations. There are only so many hours in a day to complete what needs to be done, and no matter how much you love your company, more work against a deadline can cause panic and strain.

And then there are more deadly forms of more. Conditions that you’d prefer not to experience in small or bulk quantities. One such situation is called multiple myeloma. No one wants one myeloma, let alone many. A myeloma is a type of malignant bone tumor – they rarely come on their own. They typically bring “friends” – and when a myeloma and friends show up, they bring problems that can potentially be life threatening.

What is Multiple Myeloma?

Multiple myeloma is a type of blood cancer that is a cousin of leukemia and lymphoma. It’s a cancer that occurs when normal plasma cells (cells that make antibodies that attack and kill bugs that invade your system) multiply and develop out of control – apart from the use for which they were intended. Usually plasma cells are among many blood cells found in the soft center of bones, in a place called the bone marrow. But in multiple myeloma patients, plasma cells appear in unusual quantities, and sometimes form plasmacytomas, or tumors usually found inside the bones.

As a result of the plasma cell growth, multiple myeloma patients may experience anemia (low blood count) because the plasma cells multiply in such a way that they crowd out healthy red blood cell production. White blood cell production may also become limited, and since white blood cells help to fight infection throughout the body, multiple myeloma patients may see an increase in disease that the body seems unable to fight.

Progression of the Disease

The additional plasma cells also prevent new bone structures from forming when old bone breaks down, resulting in unexpected fractures – those unrelated to external bumps and falls. Multiple myeloma is a treatable cancer, meaning there are therapeutic options such as chemotherapy, radiation, and stem cell transplantation for medical science to attempt control over the out of control cell growth. Sometimes patients can live for years with active symptoms. However, sometimes the cell growth simply is or becomes resistant to all available treatments and patients may need to turn to other forms of care as the disease progresses.

Palliative Care for Multiple Myeloma Patients

Palliative care is a medical specialty for which focuses on pain relief and symptom control rather than a curing an illness. The point of palliative care for Multiple Myeloma patients is to enhance the patient’s overall quality-of-life, allowing people to feel as good as possible. A palliative care team may focus on drug treatments to help manage bone pain typical in multiple myeloma patients as well as nausea and other forms of physical discomfort and distress.

Multiple myeloma patients also frequently suffer from reduced kidney function or failure because of the imbalanced presence of plasma cells in the blood. As the kidneys filter blood, they may become blocked by excess calcium buildup and require dialysis for comfort.

Hospice for Multiple Myeloma Patients

Hospice care is a specialized form of palliative care that is available to patients during end-of-life. Hospice also focuses on enhancing quality-of-life rather than trying to extend it. In many cases, pursuing additional treatments such as invasive treatments or difficult chemotherapy treatments can harm the patient’s quality-of-life and may not provide any benefits towards combating the disease.

The goal of hospice for cancer patients is to feel as good as possible for as long as possible. Therefore, hospice patients may receive dialysis to manage the excessive calcium blocks in the kidneys, but the treatment is mainly to help patients feel well and remain mentally oriented (excess calcium often causes disorientation in patients, rendering them unable to engage in conversation or other relational activities). By making patients more comfortable, they are able to enjoy life more fully during the time that they have remaining.

Experiencing a Peaceful Passing

Accounts of those who have accompanied a loved one as they died from complications of multiple myeloma generally report a relatively calm death in which pain has been effectively managed. Hospice providers work with physicians to measure the experience of pain a patient suffers and provide medications to alleviate discomfort while also helping them to achieve their other quality-of-life goals. Most hospice and palliative teams aim to provide care that helps patients to remain coherent, not comatose during their final days.

Manypatients make it clear that maintaining connections with their loved ones as a priority during end-of-life and this can be possible for multiple myeloma patients who elect hospice care as their disease continues to progress.

Harbor Light Hospice Is Ready to Support You!

For more information about how hospice care or palliative care can benefit multiple myeloma patients, please call us directly or, contact Harbor Light Hospice online for more information on our compassionate care services.

PMC

We met almost 3 years ago. I was in the first year of hematology and oncology fellowship training. He was in his early 60s and had recently retired. His primary care physician had referred him for evaluation of incidentally detected monoclonal proteins. Over the next few days, the workup unfolded. His skeletal radiographs showed lytic lesions, and his bone marrow biopsy showed sheets of plasma cells inundating the marrow space. It was multiple myeloma, a malignancy of plasma cells. I explained to him how these cells, which manufacture antibodies under normal circumstances, had mutated into bone-eating parasites and that his bones had become susceptible to fracture and collapse, like a fort attacked from within.

A prognostic panel showed that he had one of the most aggressive types of multiple myeloma, defined by deletion of chromosome 17p. Patients with this subtype often need aggressive treatment, respond poorly to treatment, and have worse outcomes.

Once the diagnosis sank in, he asked me, “How long do I have?”

Given his disease burden, it was clear (to me) that he needed to be treated. The unfavorable genetic profile of his disease conveyed a sense of impending crisis. However, there was a catch. He had few symptoms, if any, and was in a wonderful overall state of health. His only complaint was mild lower back pain. Most important, he did not want any treatment that would affect his quality of life. Whereas I sought to protect his excellent health through treatment, he did not think he needed to be treated. We had hit a philosophical roadblock.

Optimal treatment consisted of multidrug therapy followed by autologous stem cell transplant. As we discussed treatment-related side effects, his anxiety became palpable. It was clear that although we viewed this treatment as a “standard” approach, he viewed it—especially the transplant part—as extremely toxic. He was truly concerned about being hospitalized or missing out on a cruise with his wife or skipping a weekend with his grandchildren. What mattered to him was “not the years in his life, but the life in his years.”

I sensed his reluctance to proceed, but without treatment, he was at significant risk for disease-related complications like kidney damage, spontaneous fracture of his bones, or paralysis. I felt that some treatment was probably better than none. We negotiated, and he agreed to be treated but only with two drugs and refused the transplant.

As expected, this milder treatment program did little to reduce his monoclonal protein level. Unexpectedly, for him at least, it caused no significant side effects, and given how well he tolerated it, he agreed to try our originally recommended regimen, which consisted of three agents. Once on the triple-drug regimen, his disease burden plummeted and then plateaued at a low level, which I viewed as particularly concerning, especially in light of the aggressive nature of his disease.

It was at this point that we reintroduced the recommendation for a stem cell transplant; however, as before, each conversation about transplantation seemed to further strengthen his resolve not to have it. After another round of negotiation, we were able to collect his stem cells and freeze them for possible future transplant. He opted to continue the triple-drug regimen and tolerated it without any appreciable side effects.

Once we got over the “hump” of transplant, he seemed more at peace at subsequent visits, probably because he had avoided it. I was also more at peace because even though he refused a transplant, at least we had access to his stem cells, deep frozen.

I continued to see him in the clinic until I finished my fellowship in the summer of 2014. We have kept in touch since then, and he continues to do well. It has been almost 3 years since he was first diagnosed, and although his myeloma has not been eradicated, his disease burden and the extent of bone damage have remained stable. Although I am still unsure whether his decision to forgo transplantation was the “right” one, it made me appreciate the questions that come up quite often in the life of an oncologist: How do you define the “best” treatment? What should drive cancer care: the years in a patient’s life or the life in those years? Did I treat him, or did he teach me?

In the story of my patient, I see the amazing story of multiple myeloma. Once a death sentence, myeloma patients are living much longer now. Over the past few years, myeloma research has reached an unprecedented level of advancement. The number of approved therapies for treatment of myeloma is expanding, and drugs like bortezomib and lenalidomide have transformed the landscape of survival. In addition, two more promising drugs, pomalidomide and carfilzomib, were recently approved for refractory myeloma. Despite our progress, stem cell transplantation is still one of the best available tools for treating multiple myeloma; however, with the advent of targeted and less toxic therapies, it is likely that we will continuously re-evaluate its role in myeloma.

Even after his disease stabilized, my patient often asked me, “How long do I have?” Every time, I would tell him I honestly did not know. I loved that answer.

Physical Changes as You Near the End of Life

Medicines and medical procedures are not the only ways to help lessen your pain. There are other things you can do. Some people find distractions like music, movies, conversation, or games help. Using heat, cold, or massage on a painful area can help. Relaxation exercises and meditation can help lessen the pain and lower anxiety for some people. Keep in mind that for most people with cancer pain these measures alone are not enough to control pain. But, they may help improve comfort when used along with pain medicines.

Signs that a person is in pain

If you are a caregiver and your loved one is not able to talk about the pain they may be having, there are things you can watch for that show pain or discomfort. Signs of pain include:

  • Noisy breathing – labored, harsh, or rapid breaths
  • Making pained sounds – including groaning, moaning, or expressing hurt
  • Facial expressions – looking sad, tense, or frightened; frowning or crying
  • Body language – tension, clenched fists, knees pulled up, inflexibility, restlessness, or looking like they’re trying to get away from the hurt area
  • Body movement – changing positions to get comfortable but can’t

Being able to identify these things and give pain medicine as needed will help you keep your loved one as comfortable as possible.

You can learn more in Cancer Pain.

Appetite changes

As time goes on your body may seem to be slowing down. Maybe you find yourself eating less and losing weight. This is often experienced by people with advanced cancer, and other who are in the last stage of life.

Your body is going through changes that have a direct effect on your appetite. Changes in taste and smell, dry mouth, stomach and bowel changes, shortness of breath, nausea, vomiting, diarrhea, constipation – these are just a few of the things that make it harder to eat. Drug side effects, stress, and spiritual distress are also possible causes of poor appetite. You might feel less hungry because you’re probably moving less, have less energy, and your digestive system is slowed. It’s normal in the last stage of life for parts of your body to start slowing down. Maybe you feel full more quickly or are interested in fewer types of foods. When you eat less, the cancer cells may compete with the normal cells in your body for the nutrients that you do manage to take in and digest. This can all lead to weight loss.

What can you do about appetite changes?

It’s important to recognize changes in appetite so that you can get help when it’s needed. Talk to your medical team about how much you’ve been eating and whether you need to do something about it. For example:

  • Some causes of poor appetite can be managed with medical treatment. There are medicines that can help stimulate your appetite, decrease nausea, and help food move through your stomach more quickly.
  • A nutritionist might be able to offer tips on how to get the most out of each bite you take.
  • Supplemental drinks or shakes can sometimes help you get needed nutrition more easily.
  • You might find that you’re able to eat more when others are at the table.
  • You might find it easier to eat small frequent meals or snacks during the day instead of trying to eat full meals 3 times a day.

These measures may work for some, but they won’t help most people who are very close to the end of life. At later stages, these efforts can even make the person feel worse. (See What to Expect When a Person With Cancer Is Nearing Death.)

Avoid family food battles

It can be very upsetting to family if you start eating less. Some of them may think your interest in food represents your interest in life. By refusing food or not eating much, it may seem to your family that you’re choosing to shorten your life or that you will starve.

It’s important that you and your loved ones talk about issues around eating. The last stage of your life doesn’t have to be filled with arguments about food. Again, loss of appetite and being unable to eat happens to many people with advanced cancer. When you feel like eating less, it’s not a sign that you want to leave life or your family. It’s often a normal part of the processes that can happen in the last stage of life. If you’re getting into arguments with your loved ones, try to let them know that you appreciate their concern and understand their attempts are acts of love. You can let them know you’re not rejecting their love, but your body is limiting what it needs at this time.

You can learn more in Eating Problems.

Problems breathing

Just thinking about breathing problems can be scary. Trouble breathing and/or shortness of breath is common in people with advanced cancer, some more than others. It might not go away completely, but there are ways it can be managed.

Sometimes breathing problems make you feel short of breath, like you need to take breaths more often, or that you are breathing faster and harder than normal. You might feel like you have fluid or congestion in your throat or lungs and it makes you want to cough. Often these symptoms come and go. Tell your health care team if you’re having any problems breathing so you can get help with them.

A number of things can be done that may help make it easier for you to breathe:

  • Try sitting up, propping yourself up on pillows, or leaning over a table
  • Sometimes oxygen coming through a small tube you wear under your nose will relieve most of your symptoms
  • Opioid pain medicines can work well to decrease shortness of breath and relax your breathing
  • If there’s fluid in your lungs, medicines can be given to slow the fluid build-up
  • Sometimes opening a window, a cooler room temperature, or having a fan blowing on your face will help you feel less hungry for air
  • You can be taught breathing and relaxation techniques to use when breathing is hard
  • Medicines to reduce anxiety may help you worry less about shortness of breath

Many people with cancer fear that breathing will get worse as the disease progresses. Remember that every person’s situation is different, and it’s very hard to know exactly what will happen.

Also remember there are steps to help manage each change in your condition. Talking to your health care team and reporting what you’re feeling will let them know how they can help.

See Shortness of Breath to learn more.

Palliative care in patients with multiple myeloma

As such, palliative care (PC) is important in the maintenance of patients’ quality of life. Renato V. Samala, from the Taussig Cancer Institute, Cleveland Clinic, Ohio, US, and colleagues reviewed literature4 to discuss the rationale, timing and components of PC.

Appropriate therapeutic approach

The selection of the most appropriate treatment for patients depends upon the age of the patient, comorbidities, organ function, their ability to perform daily activities and their personal wishes.5 Ordinarily, patients with MM undergo initial therapy consisting of a combination of drugs, followed by high-dose melphalan and hematopoietic cell transplant (HCT). Maintenance therapy is then administered until disease relapse.

Classes of drugs used in the treatment of MM are outlined in table 1. Often, these drugs are used in combinations, with one example of a commonly used combination for both newly diagnosed and relapsing patients being bortezomib-lenalidomide-dexamethosone.

Table 1: Classes of drugs used in MM

Class

Examples

Proteasome inhibitors

Bortezomib, carfilzomib, ixazomib

Immunomodulatory drugs

Thalidomide, lenalidomide, pomalidomide

Corticosteroids

Dexamethasone

Alkylators

Cyclophosphamide, melphalan

Monoclonal antibodies

Daratumumab, elotuzumab

Primary clinical findings

When diagnosed, patients with MM are often at risk of other conditions, such as:

  • Bone disease:6 highly disabling, leads to pain, pathological fractures, spinal cord compression and hypercalcemia
  • Peripheral neuropathy:4 can be caused by MM, or as a side effect of therapy, such as thalidomide or bortezomib
  • Renal failure:4 arises from light chain cast nephropathy, hypercalcemia, hyperuricemia, dehydration and infections
  • Myelosuppression:4 due to MM or chemotherapy
  • Venous thromboembolism:7 can be related to patient factors (age, comorbidities, immobility), myeloma-related (disease burden) or treatment-related factors (immunomodulatory drugs combined with high-dose steroids)
  • Increased risk of infections,8 especially during active disease and treatment

Symptom burden

Due to the incurable nature of the disease, and the toxicities from the lines of treatment, the symptom burden experienced by patients with MM is profound.9 A systematic review of 36 studies10 found that at least 50% of participants experienced pain and tingling in hands and feet, constipation and fatigue; with other key symptoms being loss of appetite, dizziness, drowsiness, depression, nausea and diarrhea. The study identified that decreased social, emotional, physical and cognitive functioning were the main issues concerning quality of life.

A multicenter study11 involving 557 patients with differing stages of MM, found the most prevalent symptoms to be pain, fatigue, breathlessness, poor mobility and difficulty with memory. Many patients were concerned about carrying out day-to-day activities and worried about the future of their condition. The study found that patients with relapsed or progressive disease had the highest symptom burden and greatest concerns about quality of life.

A third study12 found that pain and fatigue were commonly reported, with concerns about quality of life echoing those observed by the larger multicenter study.11

Palliate care (PC)

A distinction needs to be made between PC and hospice care. In the US hospice care concentrates on the care of patients with a prognosis of six months or less, who are suffering from life-limiting illnesses.13 PC however, can be beneficial to patients at any stage of a serious illness, from the point of diagnosis, through treatment, and into end-of-life care.

PC can be described as the assessment and management of symptoms arising from both MM and its course of treatments. As a support system for patients, it can ensure patients continue with the treatment, and may prevent premature treatment discontinuation because of adverse effects.3

What can PC offer patients?

PC can offer patients psychosocial support throughout the course of their treatment, and as they are treated with aggressive drug regimens. Concerns about patients’ quality of life, along with support during the stable phase of the condition can lead to the coordinated management of fears and anxieties. Members of a PC team can include social workers, chaplains and PC clinicians, and can assist family caregivers in coping with the condition, accepting what is happening and planning for the future phases of the condition.

Often PC clinicians can act as bridges between patients and their oncologists, interpreting the needs of the patient back to the oncologist, and vice versa, so patients can understand and tolerate information provided by their oncologist.14

PC providers routinely facilitate care planning in advance, and consists of:

  • Reviewing goals of care
  • Discussing preferences for end-of-life care
  • Completing a living will
  • Designating power-of-attorney

When a patients’ condition becomes refractory to all treatment options, advance care planning could consist of preparation for transition to a hospice, and deciding on end-of-life care preferences.

Timing of PC

As indicated above, PC can be seen as relevant in all phases of MM. One study15 focusing on 67 patients with MM, who were referred to a PC clinic, found a significantly lower proportion of patients reporting moderate-to-severe pain, that interfered less with general activity such as sleep and mood. Fewer patients also reported depression.

Early involvement of a PC team into a patients’ routine care could build trust, and as the PC team would become acquainted with the patient and their caregivers, sensitive topics, such as end-of-life care and preferences become slightly easier to discuss. PC is often integrated late into the care of patients with hematological conditions, due to a number of reasons. At this point there may be unrealistic expectations from both the doctor and patient, an unclear definition of what advanced disease is, an unpredictable disease course that may suddenly transition from stable to late-stage, and misperception that PC is the same as end-of-life care.

Nurses, social workers, and chaplains in the PC team can address patient/carer concerns early. These can range from financial instability and psychosocial concerns, to spiritual distress and social isolation. Early involvement of a PC team can lead to better integration, assisting both the patient and the oncologist. Ultimately, the PC team would move to the forefront as the final transition to end-of-life care occurs, and the earlier the relationship between a patient, their caregivers and family, the oncologist and the PC team begins, the smoother the transition would be.

Conclusion

PC provides extra support to patients when they need it most, especially as modern medicine means that patients live longer, but are still dealing with symptoms of the condition, side effects of drugs, and everyday struggles of life. The integration of PC into oncologic care bridges the gap between patients and their oncologists, and helps to support with symptom assessment and management, and advance care planning. While it is argued that PC should be introduced early, further studies are necessary to examine the benefits of early PC.

  1. Ramsenthaler, et al. Prevalence of symptoms in patients with multiple myeloma: a systematic review and meta‐analysis. European journal of haematology. 2016 Nov. 97(5):416-29. DOI: 10.1111/ejh.12790
  2. Brenner, et al. Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood. 2008 Mar 1. 111(5):2521-6. DOI: 10.1182/blood-2007-08-104984
  3. RajeS., et al. Advances in supportive care for multiple myeloma. Journal of the National Comprehensive Cancer Network. 2014 Apr 1. 12(4):502-11. DOI: 10.6004/jnccn.2014.0055
  4. SamalaV., et al. Palliative Care in Patients with Multiple Myeloma. Journal of pain and symptom management. 2019 Jul 19. DOI: 10.1016/j.jpainsymman.2019.07.014
  5. Palumbo, et al. International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. Journal of clinical oncology. 2014 Feb 20. 32(6):587. DOI: 10.1200/JCO.2013.48.7934
  6. Terpos & Dimopoulos M.A. Myeloma bone disease: pathophysiology and management. Annals of oncology. 2005 May 31. 16(8):1223-31. DOI: 10.1093/annonc/mdi235
  7. Srkalovic, et al. Monoclonal gammopathy of undetermined significance and multiple myeloma are associated with an increased incidence of venothromboembolic disease. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2004 Aug 1. 101(3):558-66. DOI: 10.1002/cncr.20405
  8. Nucci, & Anaissie E. Infections in patients with multiple myeloma in the era of high-dose therapy and novel agents. Clinical Infectious Diseases. 2009 Oct 15. 49(8):1211-25. DOI: 10.1086/605664
  9. Jordan, et al. Effect of general symptom level, specific adverse events, treatment patterns, and patient characteristics on health-related quality of life in patients with multiple myeloma: results of a European, multicenter cohort study. Supportive Care in Cancer. 2014 Feb 1. 22(2):417-26. DOI: 10.1007/s00520-013-1991-4
  10. Ramsenthaler, et al. Prevalence of symptoms in patients with multiple myeloma: a systematic review and meta‐analysis. European journal of haematology. 2016 Nov. 97(5):416-29. DOI: 10.1111/ejh.12790
  11. Ramsenthaler, et al. The impact of disease-related symptoms and palliative care concerns on health-related quality of life in multiple myeloma: a multi-centre study. BMC cancer. 2016 Dec. 16(1):427. DOI: 10.1186/s12885-016-2410-2
  12. Boland, et al. Living with advanced but stable multiple myeloma: a study of the symptom burden and cumulative effects of disease and intensive (hematopoietic stem cell transplant-based) treatment on health-related quality of life. Journal of pain and symptom management. 2013 Nov 1. 46(5):671-80. DOI: 10.1016/j.jpainsymman.2012.11.003
  13. Teno JM, & Connor SR. Referring a patient and family to high-quality palliative care at the close of life: “We met a new personality… with this level of compassion and empathy”. JAMA. 2009 Feb 11, 301(6):651-9. DOI: 1001/jama.2009.109
  14. L., et al. Clinician roles in early integrated palliative care for patients with advanced cancer: a qualitative study. Journal of palliative medicine. 2014 Nov 1. 17(11):1244-8. DOI: 10.1089/jpm.2014.0146
  15. Porta-Sales, et al. Is early palliative care feasible in patients with multiple myeloma? Journal of pain and symptom management. 2017 Nov 1. 54(5):692-700. DOI: 10.1016/j.jpainsymman.2017.04.012

Long-term maintenance treatment with Revlimid (lenalidomide) significantly improves the length of time multiple myeloma patients live without disease worsening after their first-line therapy and, in some patients, also extends overall survival, a Phase 3 trial shows.

Findings from the trial were published in the study, “Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial,” in The Lancet Oncology.

Celgene‘s Revlimid is an immunomodulatory medicine that directly kills myeloma cells and activates the immune system to help eliminate these cancer cells. Revlimid maintenance has been shown to delay disease progression, when given after an autologous stem cell transplant — one that uses a patient’s own cells — but some studies suggest it poses no survival benefit to patients.

For patients who are not eligible for a stem cell transplant, the treatment also seems to be of benefit, when given continuously in combination with dexamethasone. However, studies have not yet examined if Revlimid maintenance has any effect on patients with high-risk genetic abnormalities, mostly because no study yet has included a sufficient number of patients for this analysis.

Thus, researchers aimed to assess the benefit of Revlimid maintenance treatment in patients with newly diagnosed multiple myeloma who achieved at least a minimal response to their first line-treatment.

The Phase 3 trial — called Myeloma XI (NCT01554852) — included 4,420 patients allocated to intensive or non-intensive induction treatment, depending on their fitness: fit patients, who were mostly younger, received chemotherapy plus an autologous stem cell transplant, while less fit, mostly older patients were given a non-intensive chemotherapy treatment.

Patients who responded were then randomized to either Revlimid maintenance (1,137 patients) or observation only (834 patients).

The primary goal of the maintenance part was to determine if Revlimid delayed disease progression or death and extended overall survival. Secondary measures included the time to disease progression or death after a third myeloma treatment, time to improved response, and toxicity.

The study included patients between the ages of 59 and 72 years, most of whom were men (61%) and white (93%). Patients had between stage I and III disease, and their genetic risk ranged from standard (51% of patients) to ultra-high (12%).

Results showed that patients receiving Revlimid lived 39 months without their disease worsening, compared with 20 months for the observation arm. This translated into a 54% reduction in the risk of disease progression or death.

The benefits in progression-free survival were seen across all subgroups, including transplant-eligible and transplant-ineligible patients, and in all risk subgroups — standard risk, high-risk, and ultra-high risk. Interestingly, while patients with complete or very good partial responses also benefited from the maintenance treatment, those with a partial or minimal response to their induction treatment appeared to benefit the most.

Revlimid did not improve the survival rates in the overall population, with 78.6% of patients living past the three-year mark, compared with 75.8% of those in the observation group. However, patients who received a stem cell transplant lived significantly longer on Revlimid than with observation only, with 87.%, versus 80.2%, of patients still alive at three years.

This survival benefit was not observed in transplant-ineligible patients, nor in any risk group, but was also seen in younger patients — an effect that researchers attribute to their eligibility for a stem cell transplant.

“This is a major breakthrough as it shows that the long-term use of lenalidomide significantly improves the time myeloma patients stay in remission after initial therapy,” Graham Jackson, MD, from the Northern Institute for Cancer Research at Newcastle University, said in a press release.

“It is a huge step and, importantly, identifies that for younger patients lenalidomide improves their overall survival for this difficult-to-treat bone marrow cancer,” added Jackson, a consultant hematologist at Newcastle’s Freeman Hospital who led the U.K.-wide study.

Despite its efficacy, more patients in the Revlimid group experienced severe adverse events (45%) than those on observation (17%). The most common serious or life-threatening adverse events among those receiving the active treatment were blood-related and included low levels of immune cells called neutrophils, low platelet counts, and anemia.

In an editorial comment in the same journal, María-Victoria Mateos MD, PhD, and Verónica González de la Calle, MD, PhD, from the University Hospital of Salamanca, attribute the lack of a survival benefit to subsequent treatments taken by the patients — some patients in the observation group received Revlimid in later treatment approaches.

“Lenalidomide maintenance seems to be effective, well tolerated, and convenient, despite the lack of overall survival benefit, because of the influence of rescue therapies in the overall survival,” they wrote.

“Maintenance with lenalidomide is the standard of care, but the future has to move towards a personalised medicine approach that aims to improve overall survival and quality of life, which means giving the right drug to the right patient at the right time for the optimal duration,” Mateo and de la Calle concluded.

  • Author Details

Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner. × Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner. Latest Posts

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