A New Era of Oral Therapies for Multiple Myeloma Implementing routines and strategies to promote adherence

TON January 2016 Vol 9 No 1 - Oral Oncolytics, Hematologic Cancers
Sabby Muneer, PhD

Recent advancements in the treatment of multiple myeloma (MM) have led to significant improvements in patient outcomes, including unprecedented survival rates. Such progress has allowed a paradigm shift toward a chronic care model, with attention increasingly focused on improving patients' quality of life. This MM treatment evolution has ushered in a new era of oral anticancer agents. Several of these therapies are currently approved by the US Food and Drug Administration, including thalidomide, lenalidomide, pomalidomide, and panobinostat, as well as others that are in clinical development.2 There are numerous benefits to these oral oncolytic therapies. They are easier and faster to administer, less invasive, and more flexible and convenient than injections and infusions, resulting in minimal disruption of patients' activities of daily living, and improvements in their quality of life.

The advent of oral anticancer agents has had a major impact on the practical management of MM; they are challenging traditional attitudes toward myeloma care, redefining the roles and responsibilities of providers and patients, and demanding a new model of oncology services for patient education, monitoring, and support. Importantly, the incorporation of oral oncolytic therapies has caused a shift in medication responsibility. Although healthcare providers are traditionally responsible for the administration of intravenous medications, this burden has now shifted to patients, creating new challenges for healthcare professionals to maintain medication adherence.3

This monograph reviews these emerging concepts that were developed to address the unique issues presented by the increasing use of oral therapies, with a focus on their relevance to oncology nurses and nurse navigators, considering their essential role in the oncology team, and their presence on the frontline of MM care.

Barriers to Adherence

Adherence is defined as the extent to which a patient's behavior coincides with instructions from a healthcare provider. Nonadherence is associated with suboptimal drug efficacy, resulting in poor clinical outcomes and increased healthcare costs.5 Medication nonadherence is identified as the largest driver of avoidable US health-care costs, accounting for > $200 billion annually.6 Unfortunately, available reports indicate that nonadherence to oral oncolytic therapy is rampant, ranging from < 20% to 100%, contrary to healthcare providers' assumptions that it is a nonissue compared with the gravity of the disease.7 Because of the clinical and economic implications of nonadherence to oral oncolytic therapies, it is imperative that healthcare providers acknowledge and address the unique issues of adherence.

Adherence behavior has been proposed as a continuum from fully adherent to totally nonadherent, and can be classified into 6 behavior types, including adherer, partial adherer, overuser, erratic user, partial dropout, and dropout.8,9 The reasons dictating adherent behavior may differ for each patient's situation. Many barriers to medication adherence have been identified that may be broadly grouped as treatment-, patient-, physician-, and environment-related variables.3-5 Patient-related factors may include poor understanding of the disease and associated risks, a perception of being cured or having asymptomatic disease, a lack of belief in treatment benefits, reluctance to change behaviors, age and sex, cognitive impairment (eg, forgetfulness), comorbid conditions, and polypharmacy.

Treatment-related factors, such as medication side effects and drug-drug interactions, can result in medication nonadherence when the patient is unprepared or unable to manage his or her symptoms. In addition, the complexity of the regimen, such as a complicated dosing schedule, may negatively impact the patient's ability to follow a regimen; typically, longer treatment duration is associated with noncompliance. Physician-related barriers include poor patient-provider communication, lack of positive reinforcement from the healthcare provider, insufficient educational measures on the medication regimen or importance of adherence, and infrequent follow-up. Socioeconomic factors, such as lack of health insurance, medication cost, limited access to healthcare facilities and/or pharmacies, social lifestyle, lack of family or social support network, and inadequate supervision, are also strong determinants of medication nonadherence.

Because of these varied logistic, perceptual, physiologic, and social impediments to treatment, it is critical that healthcare providers identify individual barriers to, and facilitators of, oral oncolytic therapy, and work with patients to isolate strategies that would enable them to take their medications as prescribed. In the practice context, the onus of identifying and addressing specific patient adherence barriers falls largely on oncology nurses and nurse navigators, owing to their skills of helping patients with side effect management, procurement, routine handling of medications, and follow-up care. Indeed, nursing interventions have been shown to positively impact medication adherence, as well as symptom management.10,11

Medication Adherence Assessment

In providing patient-centered oncology care, it is important to perform routine assessments of medication adherence to oral therapies. There is no gold standard medication adherence measurement, but several strategies are available that may be broadly grouped as direct and indirect methods, as outlined in Table 1; each has its own advantages and limitations, and may not assess all aspects of prescription adherence.12 Direct methods include directly observed therapy, measurement of the level of a drug or its metabolite in blood or urine, and measurement of a biologic marker in the blood. Direct approaches are one of the most accurate methods of measuring adherence, but they are expensive and may require additional physician visits that could compromise patient convenience.


Indirect methods include patient questionnaires, patient self-reports, pill counts, rates of prescription refills, assessment of the patient's clinical response, electronic medication monitors, measurement of physiologic markers, and patient diaries.7,12 However, these methods are subjective and susceptible to alteration by patients, inaccurate data entries, recall bias, or errors because of increased intervals between patient visits. Patient questionnaires and self-reports are simple, inexpensive, and widely used in clinical settings, although they may be easily distorted by patients. Pill counts may also be easily manipulated, and do not provide information about adherence to the dosing schedule. Using pill containers with a microelectronic monitoring system allows for tracking of the opening of the pill container, but this cannot be correlated with pill ingestion, and is cost-prohibitive. Evidence of a clinical response can confirm patient adherence to oral medication, but be affected by other factors. Assessing prescription filling and insurance records is considered to provide the most accurate estimate of actual medication use over a period of time; however, it does not necessarily translate to pill consumption, or provide information about whether the patient is taking the medication as prescribed.

Interventional Strategies to Improve Medication Adherence

It is well-accepted that improving patient adherence requires a multifaceted approach, and cannot rely on one method. Typically, models of adherence interventions are based on the key elements of patient education, behavioral interventions, and affective support, which may include symptom management, simplifying medication regimens, improving patinet-provider communication, and applying reminder cues, as outlined in Table 2.3 In fact, a Cochrane review recently found that successful adherence interventions for long-term care involved education, reminders, self-monitoring, reinforcement, counseling, family and caregiver therapy, psychological therapy, crisis intervention, manual telephone follow-up, and supportive care.13,14 Importantly, because of the lifestyle differences among patients, identifying individual barriers and tailoring adherence interventions to their individual needs is critical.15


Foremost, patient education regarding the disease, treatment plan, risks and benefits of treatment, side effects, drug-drug or drug-food interactions, and importance of adherence is essential to ensure that oral oncolytic therapies are being taken correctly.3,16 Education may alleviate patients' fears and concerns regarding the side effects of the prescribed drugs, and must include early recognition signs, how to proactively prevent side effects with supportive agents, and how and when to contact their healthcare provider.3,16 In addition, all concomitant medications must be reviewed with the patient to avoid potential drugs that may cause additional adverse events.3 During counseling, the unique characteristics of an oral drug treatment plan must be emphasized, including the patient's role in managing his or her drug administration, the patient's responsibility to report these effects to the oncology care team, the importance of adherence, and that patients are entering into a partnership with their healthcare provider.17 Ongoing education must be implemented as part of routine care for patients receiving oral oncolytic therapies; working from a check-off list may be helpful, and may ensure consistency and completeness of information.17

Instructions and information pamphlets that are provided during counseling in the clinic setting alone may not be sufficient for many patients. In addition, patients may need clear, simple, written instructions for reference at home regarding correct medication dosing and timing, as well as the adverse consequences of missing or rationing doses.3 A comprehensive treatment plan that includes the goal of therapy, timing and dosing of therapy, special considerations, monitoring and follow-up procedures, and symptom management must also be provided.17

The frequency of monitoring and follow-up strategies, such as office visits, Internet-based patient portals, and phone-based check-ups that are appropriate for the patient and the oncolytic agent prescribed must be determined and defined in the treatment plan.18 It is recommended that an office visit is scheduled once per cycle for an assessment; most importantly, follow-up visits, calls, e-mails, or text message reminders must be used as opportunities to reiterate the importance of adherence.19 During these follow-up visits, medication adherence must be assessed, and any identified barriers must be addressed.

The Health Belief Model allows for better understanding of patients' motivations, beliefs, and barriers to facilitate appropriate adherence interventions.20 This model consists of 5 concepts, including perceived susceptibility, perceived severity, perceived benefits, perceived barriers, and cues to action. Other concepts, such as self-efficacy and facilitation, may also be incorporated to define a workable model in everyday practice, as shown in the Figure.20

Perceived susceptibility is defined as patients' beliefs about their risk of disease progression, symptom worsening, and survival with and without medication, whereas perceived severity is patients' beliefs on the extent of their disease severity; together, they account for the perceived threat of myeloma.20 This understanding is essential for patients to make a change in their adherence behavior. Oncology nurses and nurse navigators need to work with patients to educate them about the disease threat based on patients' baseline levels of understanding. On a related note, perceived benefits refer to patients' understanding of the short-and long-term efficacies of their prescribed oral oncolytics for myeloma control; perceived barriers are patient-specific barriers to medication adherence.20 Oncology nurses and nurse navigators need to identify and address individual barriers, and convey that the benefits of medication adherence outweigh the barriers.

Facilitation is defined as the process of providing the tools and resources necessary to enable patients to adhere to their medications. Oncology nurses and nurse navigators need to address any modifiable factors that have been identified. Before the initiation of an oral regimen, the best practice is to conduct an assessment of the patient's ability to obtain the drug and administer it according to the treatment plan, along with a plan to address any identified issues. The assessment should include socioeconomic, psychosocial, financial, administrative, and regulatory factors that may influence initiation and/or adherence to the prescribed regimen.18 In this context, oncology nurses and nurse navigators may also need to assist patients with medical access and acquisition, and work with insurers and oncology pharmacists to complete the authorization processes, understand the refill policy and medication delivery time frame, and determine a start date.17 They may also need to connect patients with prescription drug assistance programs to enable patients to afford their medications. Thus, the role of oncology nurses and nurse navigators is to reduce barriers to adherence, and provide patients with the skills and resources necessary to adhere to medications after the intervention ends. To facilitate adherence behavior, the navigator will need to employ cues to action that are individually tailored to the patient's specific needs. The cues may be in the form of e-mails, text messages, or phone calls depending on the patient's preference.

Self-efficacy can be defined as a patient's belief in his or her ability to engage in the behaviors necessary to adhere to oral medication.7 To improve self-efficacy, oncology nurses and nurse navigators must be trained in motivational interviewing techniques to engage the patient in discovering and developing new beliefs, expectations, and strategies for overcoming barriers to adherence.19 Motivational interviewing emphasizes more patient engagement, and several other techniques-such as reflective listening and the use of open-ended querstions-are more effective methods to assess adherence, identify barriers, and establish adherent behavior, as well as a nurse-patient collaborative partnership. In contrast to traditional health-care provider-driven counseling that dictates certain behavioral changes and does not focus on patient engagement, motivational interviewing respects patients' self-determination, acknowledges autonomy, and recognizes that the patient decides whether or not to change his or her own behaviors. In this context, the concept of change theory may also be applied to modify adherence behaviors, and focuses on the decision-making abilities of the individual rather than the social and biological influences on his or her behavior.

Adherence Tools and Resources

Patients should be encouraged to use adherence aids and reminder cues to improve adherence outcomes.3 There are several reminder triggers that can be used to improve patients' adherence to their oral therapies, such as pillboxes, pill diaries, and treatment calendars.15 Reminders set up on the phone or with text messages based on the dosing schedule are popular methods that may be employed. Calendars, checklists, and postcards or e-mails may be used as refill reminders so that patients have an adequate supply of medications.

The Oncology Nursing Society has developed an oral adherence toolkit that includes tools, resources, and information for interventional strategies that nurses may employ to promote medication adherence.12 These include information on adverse effects and drug-drug interactions associated with common oral drugs, adherence assessment methods, sample treatment calendars and schedules that map a weekly oral treatment, pharmacy and reimbursement/financial resources to direct patients to financial assistance, motivational interviewing, and counseling, as well as concept of change theory.12 The medication calendar typically maps out a weekly oral treatment plan, and includes the number of pills per dose, the number of doses per day, and times to take the medication. Patients can then record the times their medication was taken.12 The Multinational Association of Supportive Care in Cancer Oral Agent Teaching Tool is a framework that helps clinicians identify barriers and facilitators to adherence; ensures that adherence assessment, symptom management, and adherence strategies are addressed; provides suggestions for patient education; and provides examples of its usefulness in clinical settings.21



The advent of oral oncolytic therapy predicts a future of effective, convenient regimens for patients with MM; however, this will necessitate changes in current management practices. To optimally implement best practices, all stakeholders in the delivery of care to patients with MM-inclusing physicians, oncology nurses, nurse navigators, patients, and caregivers-must be engaged in the process and collaborate effectively to ensure adherence to oral oncolytic therapy.


1. Kyle R. Historical overview of multiple myeloma therapy. Managing Myeloma. www.managingmyeloma.com/ knowledge-center/commentary/810-historical-overview-of-multiple-myeloma-therapy. Updated March 13, 2014. Accessed August 27, 2015.
2. CenterWatch. FDA approved drugs for oncology. www.centerwatch.com/drug-information/fda-approved-drugs/ therapeutic-area/12/oncology. Accessed August 27, 2015.
3. Cheung WY. Difficult to swallow: issues affecting optimal adherence to oral anticancer agents. Am Soc Clin Oncol Educ Book. 2013:265-270.
4. World Health Organization. Adherence to long-term therapies: evidence for action. http://apps.who.int/medicinedocs/ en/d/Js4883e. 2003. Accessed October 15, 2015.
5. Accordino MK, Hershman DL. Disparities and challenges in adherence to oral antineoplastic agents. Am Soc Clin Oncol Educ Book. 2013:271-276.
6. IMS Institute for Healthcare Informatics. Avoidable costs in U.S. health care. www.imshealth.com/deployedfiles/ imshealth/Global/Content/Corporate/IMS%20Institute/RUOM-2013/IHII_Responsible_Use_Medicines_2013.pdf. Published June 2013. Accessed October 10, 2015.
7. Partridge AH, Avorn J, Wang PS, Winer EP. Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst. 2002;94:652-661.
8. Vander Stichele R. Measurement of patient compliance and the interpretation of randomized clinical trials. Eur J Clin Pharmacol. 1991;41:27-35.
9. Kehoe WA, Katz RC. Health behaviors and pharmacotherapy. Ann Pharmacother. 1998;32:1076-1086.
10. Schneider SM, Adams DB, Gosselin T. A tailored nurse coaching intervention for oral chemotherapy adherence. J Adv Pract Oncol. 2014;5:163-172.
11. McCauley KM, Bixby MB, Naylor MD. Advanced practice nurse strategies to improve outcomes and reduce cost in elders with heart failure. Dis Manag. 2006;9:302-310.
12. Oncology Nursing Society. Tools for oral adherence toolkit. www.ons.org/sites/default/files/oral%20adherence %20toolkit.pdf. Updated December 24, 2009. Accessed October 15, 2015.
13. Nieuwlaat R, Wilczynski N, Navarro T, et al. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2014;11:CD000011.
14. Haynes RB, Ackloo E, Sahota N, et al. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2008:CD000011.
15. Schneider SM, Hess K, Gosselin T. Interventions to promote adherence with oral agents. Semin Oncol Nurs. 2011;27:133-141.
16. Jimmy B, Jose J. Patient medication adherence: measures in daily practice. Oman Med J. 2011;26:155-159.
17. Pagan J. Managing oral oncology/hematology treatments in your practice. Arizona Oncology. http://arizonaoncology. com/news/article/managing-oral-oncology-hematology-treatments-in-your-practice. Accessed October 18, 2015.
18. Neuss MN, Polovich M, McNiff K, et al. 2013 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards including standards for the safe administration and management of oral chemotherapy. J Oncol Pract. 2013;9(Suppl 2):5s-13s.
19. Lombardi C. Patient adherence to oral cancer therapies: a nursing resource. Oncolink. www.oncolink.org/ resources/article.cfm?c=424&id=7058. Updated May 23, 2014. Accessed October 15, 2015.
20. Janz NK, Becker MH. The health belief model: a decade later. Health Educ Q. 1984;11:1-47.
21. Multinational Association of Supportive Care in Cancer. MASCC oral agent teaching tool (MOATT). www.mascc. org/MOATT. Accessed October 18, 2015.


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Last modified: February 16, 2016