Palliative care in patients with multiple myeloma

Multiple myeloma (MM), the second most common hematologic malignancy after non-Hodgkin lymphoma,1 is responsible for around 20,000 deaths in Europe and 13,000 deaths in America per year.1 A number of successful clinical trials, a better understanding of MM disease pathology, and the identification of novel targets and disease-modifying therapies, has meant that MM is now highly treatable.  While the condition remains incurable, taking the form of response and relapse, spanning many years, overall survival has increased from 30% in the 1990’s, to 40% in the early 2000’s,2 resulting in a number of patients living longer with the disease.3

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.

References

  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. BackL., 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

Expert Opinion

"This is an excellent article by Samala et al. arguing for the inclusion of palliative care at all stages of treatment for patients with multiple myeloma (MM).  The authors discuss the importance of maintaining a good quality of life (QoL) for those with symtomatic MM, through the integration of palliative care early in the patient's treatment pathway.

Samala et al. identify how debilitating symptoms such as pain, fatigue, constipation and other treatment-related side effects, such as neuropathy and insomnia, can be managed, and the burden of symptoms reduced, by the integration of palliative care.

MM is now a chronic disease with patients surviving over many years due to a number of highly effective treatment modalities; yet the disease remains incurable and this is something patients have to live with.  This is a timely article, which defines palliative care as essential to good QoL when living with MM.  Palliative care, as the authors highlight, enables an 'extra layer of support' to patients when managing the high symptom burden associated with MM, as well as with the social and psychological implications of living with a cancer that is now considered a chronic disease.

The authors have a very important message about QoL for this group of patients to enable symptom and psychosocial support by integrating palliative care throughout the disease trajectory of MM - something that is really needed for this group of patients."

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