Overview of Multiple Myeloma
Multiple myeloma (MM) is a hematologic malignancy involving a type of white blood cells known as B lymphocytes. This cell type further differentiates into plasma cells that generate antibodies during an infection or other physical insult. In MM, the plasma cells continue to make protein antibodies and accumulate in the bone marrow leading to dysfunction. There, malignant cells grow to form tumors or lesions throughout the body. MM is characterized by localized tumors of plasma cells called plasmacytomas, which can grow in and out of the bone.1 Hallmark symptoms of myeloma include weakness, anemia-related fatigue, bleeding/bruising, decreased ability to fight infections, kidney damage, or other organ damage. In addition, as myeloma weakens the bones, patients are at risk for fractures, which leads to significant pain.
MM, a blood cancer representing about 2% of all new cancer cases, is considered predominantly a disease of older adults.1,2 The median age at diagnosis is 69 years, but the incidence in younger adults aged 20 to 49 years is rising. Risk factors for MM include age, race (African Americans are twice as likely to be diagnosed), gender (men are at a 1.5× risk), and family history. Initial testing for myeloma includes serum or urine electrophoresis and free light chain assay, but a definitive diagnosis requires a bone marrow aspirate and biopsy.3 To date, there has been no named “cure” for myeloma. However, the survival rate has improved significantly over the past decades. Overall outcome advantages are dependent on the stage of disease at the time of diagnosis, the patient’s age, overall health, and the natural progression of the disease, which varies by the individual. There is a 75% 5-year survival rate for patients diagnosed with early-stage MM.4
History of Myeloma/Treatment
MM was first characterized in 1844 and named in 1889.5 Early treatments included rhubarb and leeches, and the first drug was not used until 1947.5 In 1962, melphalan became the first chemotherapy agent used.5 Advances in treatments have resulted in dramatic survival improvements, from 12% in 1960 to 1963 to 53.7% from 2009 to 2015.6
The selection of initial therapy for patients with MM depends on disease risk stratification, the patient’s eligibility for autologous hematopoietic stem cell transplantation, and a comprehensive assessment of comorbidities. For patients who are ineligible for transplants, triplet regimens are utilized. One of the most common frontline therapies, known as RVD or VRD, includes bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone. Alternative therapies such as CyBorD (cyclophosphamide, bortezomib, and dexamethasone), DRd (daratumumab, lenalidomide, and dexamethasone), and KRd (carfilzomib, lenalidomide, and dexamethasone) are also considered triplet therapy options for patients who cannot tolerate certain drugs or who may not be eligible for transplant.3
Over recent decades, the introduction of new chemotherapy combinations, targeted small-molecule inhibitors, and monoclonal antibodies has improved outcomes. The evolving treatment options offer patients more extended disease control and improved outcomes, transforming them to become more functionally curable. The recently approved monoclonal antibody daratumumab has become a favorite for later-line induction regimens. Other monoclonal antibodies approved include elotuzumab and isatuximab.3 Another area of interest, along with utilizing monoclonal antibodies, is B-cell maturation antigen (BCMA) targeting. Recent clinical trials include evaluation for emerging therapies such as BCMA and CAR T-cell therapies.
Clinical Trials, So What?
Treatment advances occur largely through the clinical trial process. Cancer is a leading cause of death in the United States, with an estimated 1.8 million new cases diagnosed in 2020, resulting in 606,520 deaths.7 In 2015, less than 5% of adult patients with cancer enrolled in clinical trials,8 while today, that has risen to 8%.9 Unger and colleagues found in a systematic literature review that about half of the patients approached in consideration for research participation agreed to volunteer.9 These rates were similar regardless of race: white, black, Hispanic, and Asian.9
Part of the oncologic clinical trial spectrum includes the hope for an eventual cure for MM. In addition, ongoing trials will allow providers to incorporate novel cutting-edge therapies to induce more profound responses.10 There are several types of research activities that can be encountered in the clinical setting. Health services research is conducted to determine patterns of care, use of services by healthcare stakeholders, or the impact of events on healthcare, such as the impact of COVID-19 on patients. These research activities can use methods such as quality-of-life surveys or data abstraction from the standard-of-care treatment. Other research efforts may focus on biological specimen collection and long-term follow-up using a registry approach. These trials are not designed to set a hypothesis but to contribute to scientific knowledge by acquiring new knowledge. New treatments are evaluated through clinical trials.
Clinical trials are designed to test treatments and are categorized by phases. The earlier-phase trials are designed to find the optimal dose for testing and to identify potential toxicities. The later-phase trials gather the data for FDA approval by comparing the safety and efficacy of the investigational drug with the standard of care. Important considerations for patients involved in clinical trials are to support patients for 100% medication adherence to ensure the data are usable to support an approval application to the FDA. MM treatment regimens can be challenging with triplet and now quadruplet regimens being tested in clinical trials. When patients involved in trials have poor adherence, questions about efficacy and toxicities cannot be adequately answered.
Research teams are configured according to the size of the facility. All clinical trials are led by a principal investigator, who is a physician for most clinical trials. Members of the research team may also include study coordinators, data managers, regulatory associates, and other operational members involved in finance and management. Study coordinators may or may not be nurses. The role of a study coordinator is to ensure that the clinical trial is conducted according to the research protocol and institutional review board requirements. Study coordinators ensure that research procedures are completed in a timely fashion as specified by the protocol to yield usable data and to protect research participants’ rights. Procedures that may be normally encountered in routine care may have defined parameters for a research protocol. For example, even vital signs may require a specific period of rest, blood pressure measurements in both arms or the same arm across all measurements in the study, and a particular patient positioning. If these criteria are not documented and followed, then the vital signs may be considered unusable as data points and result in a protocol deviation. All data in a clinical research study must be collected in a prescribed fashion to allow data analysis across all patients at all sites to be considered equivalent. This example is offered to increase awareness about the intricacies of clinical research and the value of each data point. Careful consideration must be given for changes in scheduling or orders because these intricate requirements may be unknowingly violated with detrimental effects. Clinical trial data abstracted from the medical record and entered into a research database are regularly reviewed against the medical record for accuracy and completeness by external monitors.
Institutional review boards are committees required by federal and international agencies to oversee all human subject research to ensure the protection of participants. The committee functions from a platform of regulations and ethical principles. The study sponsor writes a research protocol to outline the procedures required for the study, while the institutional review board approves plans for obtaining research consent, reporting adverse events, and protocol deviations. Serious adverse events, such as hospitalizations, are required to be reported using an extensive form to the sponsor and institutional review board within 24 hours. There is overlap between the stakeholder functions to support achieving the goals for clinical research. All aspects of clinical research are reviewed and approved by multiple layers of protective bodies.
The Role of the Nurse Navigator in the Clinical Trials Process
Nurse navigators may interact with the physician-researcher and the coordinator when patients choose to receive cancer care through a clinical trial. Role delineation and collaboration can enhance the workflow processes and professional development between nurse navigators and clinical research team members. It is essential for the nurse navigator to participate as a key member of the multidisciplinary team, assisting with patient education and ensuring that patients are given fair access to all treatment options to make a well-informed decision about their care.
One of the hallmarks for nurse navigators is the importance of eliminating barriers to care. Social, emotional, educational, and financial barriers are often present and preclude patients from initiating or complying with prescribed treatments. Some barriers to clinical trials enrollment are not patient-specific but relate more to organizational processes and trials availability. Some of these include language and cultural barriers impacting communication, scheduling challenges for appointments and procedures, and distance for care from research centers for patients in rural settings.11 Minority patients are particularly underrepresented in clinical trials, and working to eliminate barriers can help improve enrollment and retention of this patient population.12 Navigators can “stand in the gap” for and with patients during clinic visits, where they can help patients understand complex information about their treatment regimens and required protocols.
The nurse navigator serves as a patient advocate throughout the healthcare continuum. They may assist with identification and screening for potential candidates for clinical trials and help advocate for care that is driven from a patient-centered perspective. Furthermore, the nurse navigator may help patients overcome fear and myths about trials. Developing and maintaining trust is essential in the navigator and patient relationship. When patients are followed by a navigator, they know they have mutual support and understanding about their unique situation and how it relates to the entire continuum of their cancer care journey.
For the nurse navigators to ensure they are providing best-practice care for patients as it relates to clinical trials, they must be supported from a professional and organizational perspective. The navigators should engage in continuous educational opportunities aimed at developing an understanding and awareness of historical and current aspects of the clinical trials paradigm. Novice nurse navigators should receive training and should engage with their local clinical trials or research office for a mutual understanding of best practices in both patient navigation and the clinical trials processes.
For navigation programs to meet accreditation requirements through the Commission on Cancer, nurses must meet and maintain educational standards or obtain certification as an oncology certified nurse (OCN).13 The OCN testing content includes a scientific basis for practice that includes understanding the themes and trajectory of clinical trials as they relate to patient care.14 Continuing education opportunities for navigators that include treatments should include topics related to clinical trials to help nurses maintain competency and confidence about this paramount topic.
Mr Smith is a 74-year-old African American male who lives in a medically underserved rural county. He is recently widowed and lives alone in a small house adjacent to the farm where he worked all his life. He has 2 grown children who are supportive but reside in other states. Mr Smith is active in his small community and regularly attends church. He counts himself as lucky because he never had to go to the hospital except for a couple of minor farming injuries. He has no diagnosed conditions and does not take any medicines.
Mr Smith has been referred to a community-based hematology-oncology practice 2 hours away with complaints of fatigue, anemia, bone pain, and mildly elevated creatinine. The patient was evaluated in the clinic, and a bone marrow procedure confirmed the diagnosis of MM. The attending physician consults nurse navigation to assess this new patient and the clinical trial coordinator to determine the patient’s eligibility for a new research trial.
Mr Smith has decided to enroll in a new clinical trial and will be the first participant placed on the study from this site. The study involves randomizing research participants between 2 arms: one standard-of-care arm with intravenous therapy and the investigational arm involving daily dosing of oral medications. The patients will go to transplant as part of the study on the first remission. The participants will be eligible to receive investigational medications delivered to their homes after the first 2 cycles and for some telehealth visits to reduce onsite follow-up. In addition, patients may have some labs drawn at a local provider upon verification by the sponsor. The nurse navigator and clinical coordinator discuss the patient.
The nurse navigator is experienced in caring for patients diagnosed with MM but has not worked with a research patient on a study before. The clinical coordinator is experienced with research but has just transferred from an inpatient research position to the oncology research office. The collaborative opportunities between the nurse navigator and the clinical research coordinator are summarized in the chart below.
- Aguaron A, Armour M, Biru Y, et al. Uncovering the unmet needs of people living with multiple myeloma. Conquer: the patient voice. https://conquer-magazine.com/issues/special-issues/unmet-needs-people-living-multiple-myeloma. 2017.
- Chakraborty R, Majhail NS. Treatment and disease-related complications in multiple myeloma: implications for survivorship. Am J Hematol. 2020;95:672-690.
- Padala SA, Barsouk A, Barsouk A, et al. Epidemiology, staging, and management of multiple myeloma. Med Sci (Basel). 2021;9:3.
- American Society of Clinical Oncology. Multiple Myeloma: Statistics. www.cancer.net/cancer-types/multiple-myeloma/statistics. 2021.
- Ribatti D. A historical perspective on milestone in multiple myeloma research. Eur J Haematol. 2018;100:221-228.
- Leukemia & Lymphoma Society. Facts and Statistics Overview. www.lls.org/facts-and-statistics/facts-and-statistics-overview/facts-and-statistics.
- National Cancer Institute. Cancer Statistics. www.cancer.gov/about-cancer/understanding/statistics. 2020.
- Unger JM, Cook E, Tai E, Bleyer A. The role of clinical trial participation in cancer research: barriers, evidence, and strategies. Am Soc Clin Oncol Educ Book. 2016;35:185-198.
- Unger JM, Hershman DL, Till C, et al. “When offered to participate”: a systematic literature review and meta-analysis of patient agreement to participate in clinical trials. J Natl Cancer Inst. 2021;113:244-257.
- Branagan A, Lei M, Lou U, Raje N. Current treatment strategies for multiple myeloma. JCO Oncol Pract. 2020;16:5-14.
- Holmes DR, Major J, Lyonga DE, et al. Increasing minority patient participation in cancer clinical trials using oncology nurse navigation. Am J Surg. 2012;203:415-422.
- Uveges MK, Lansey DG, Mbah O, et al. Patient navigation and clinical trial participation: a randomized controlled trial design. Contemp Clin Trials Commun. 2018;12:98-102.
- American College of Surgeons. Commission on Cancer. Optional resources for cancer care: 2020 standards. www.facs.org/-/media/files/quality-programs/cancer/coc/optimal_resources_for_cancer_care_2020_stan dards.ashx. 2020.
- Oncology Nursing Certification Corporation. Oncology Certified Nurse (OCN) Test Content Outline. www.oncc.org/files/2018OCNTestContentOutline.pdf. 2018.