Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in western countries.1-4 Accounting for nearly one-third of all leukemias in the United States, CLL is predominantly a disease of aging with two-thirds of patients being over age 65.1-5 It’s clinical course can range from an indolent, chronic condition, to one that rapidly leads to premature death.6
Recent genomic investigations have characterized CLL as a molecularly heterogeneous malignancy. Multiple chromosomal aberrations are responsible for this diversity and also influence prognosis.3 The CLL genome for example, carries more than 2,000 molecular lesions, including more than 20 nonsynonymous mutations and approximately five gross structural abnormalities.6 Deletions of the long arm of chromosome 13 is the single most observed cytogenetic aberration occurring in more than half of all cases.2, 3
CLL is most frequently diagnosed in asymptomatic patients when leukocytosis or lymphocytosis is accidentally identified in routine complete blood cell count evaluations.1 The diagnosis requires the presence of > 5,000 B lymphocytes in the peripheral blood for 3 months.2 Treatment is usually deferred until patients become symptomatic. However, patients with high-risk genomic features may be treated prior to symptom presentation.
Chemoimmunotherapy including fludarabine, cyclophosphamide, and rituxamab (Rituxin, FCR) is the standard first-line therapy.1, 4, 7 Patients with comorbidities and poor performance status may be prescribed monotherapy with chlormabucil (Leukeran), the agent historically used as initial therapy for CLL.2 Bendamustine (Treanda), a unique cytostatic agent containing both alkylating agent and purine analog properties, is now available for first-line treatment of patients not eligible for FCR.1 The targeted agents ibrutinib (Imbruvica) and idelalisib (Zydelig), small molecule inhibitors that impede pathways genetically altered in CLL, were approved for relapsed/refractory CLL in 2014.1, 7, 8
Recent small-scale trials have investigated these agents combined with rituximab in older patients.4 Other immunomodulating drugs such as lenalidomide (Revlimid) are being studied as single agents in dose-escalation studies in older patients.4 Yet, while an array of contemporary treatment options are available for this B-cell malignancy, it remains incurable with current therapy options.3 The exception is in cases where CLL patients are offered allogeneic hematopoietic cell transplantation (allo-HCT), especially in those with high-risk cytogenetic profiles.9
The rapid change characterizing the contemporary management of CLL is an exemplar of how scientific discovery can change the landscape of an individual malignancy, However, with this evolution comes many new challenges that have particular relevance to oncology nursing practice.
First is prevalence. With a growing aging society, we can expect more cases of CLL.2 Knowledge about how to treat a very heterogeneous older population, namely the fit, those with some physical compromise, and the frail, all require investigation, Second, is how to address adherence in this increasing paradigm of oral therapies. Our knowledge base in expanding on the deleterious effects of nonadherence in terms of treatment outcome. This phenomenon is a very nurse-sensitive construct that requires focused attention.
Oral therapies also switch the treatment venue to one out of our control. Patients are expected to oversee their care on their own. These problems are not related to cytotoxic therapies but from targeted and immune-modulating ones. Is the patient’s less than ideal control of their diarrhea associated with ibrutinib impacting their skipping doses? Or is it the out-of-pocket expenses associated with treatment? This issue of “financial toxicity” is a real one. Two studies of the effect of out-of-pocket expenses on treatment adherence revealed that even with as little as $30 up to a $500 co-pay, was associated with treatment abandonment.10-12 Of particular note is an estimated 10-year hypothetical pharmaceutical cost of $35,564 per person for 100 newly diagnosed CLL patients on Medicare Part D assuming the cost of ibrutinib as first-line therapy.13
A “chemo-free future” portends a new host of patient care concerns.7 Oncology nurses must begin to embrace this new destiny as different issues will require our patient advocacy. Changing toxicity profiles, increased reliance on self-management of symptom distress, and financial burden, will require novel thinking of how best to support this growing cohort of patients.
How are you preparing for this new landscape of care?
- Smolej L, Simkovic M. Practical approach to the management of chronic lymphocytic leukemia. Arch Med Sci. 2016 Apr 1; 12(2): 448–456.
- Hallek M. Chronic lymphocytic leukemia: 2015 update on diagnosis, risk stratification, and treatment. Am J Hematol. 2015 May;90(5):446-60.
- Delgado J, Villamor N, Lopez-Guillermo A, Campo E. Genetic evolution in chronic lymphocytic leukaemia. Best Pract Res Clin Haematol. 2016 Mar;29(1):67-78.
- Bachow SH, Lamanna N. Evolving Strategies for the Treatment of Chronic Lymphocytic Leukemia in the Upfront Setting. Curr Hematol Malig Rep. 2016 Feb;11(1):61-70.
- Eichhorst B, Dreyling M, Robak T, et al. Chronic lymphocytic leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011 Sep;22 Suppl 6:vi50-4.
- Rossi D, Gaidano G. The clinical implications of gene mutations in chronic lymphocytic leukaemia. British J Cancer. (2016) 114, 849–854.
- Jain N, O’Brien S. Targeted therapies for CLL: Practical issues with the changing treatment paradigm. Blood Rev. 2016 May;30(3):233-44.
- Koffman B, Schorr A. The 21st century revolution in CLL: Why this matters to patients. Best Pract Res Clin Haematol. 2016 Mar;29(1):122-132.
- Kharfan-Dabaja MA, Kumar A, Hamadani M, et al. Clinical Practice Recommendations for Use of Allogeneic Hematopoietic cell transplantation in Chronic Lymphocytic Leukemia on Behalf of the Guidelines Committee of the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2016 Sep 19.
- Gleason PP, Starner C, Gunderson BW. Oral Oncology Prescription Abandonment Association with High Out-of-Pocket Member Expense. J Manage Care Pharm. 2010;16: 161-162.
- Neuget A, Subar M, Wilde ET. Association with prescription co-payment amount and compliance with adjuvant hormonal therapy in women with early-stage breast cancer. J Clin Oncol. 2011 Jun 20;29(18):2534-42.
- Zafar SY, Peppercorn JM, Schraq D, et al. The financial toxicity of cancer treatment: A pilot study assessing out-of-pocket expenses and the insured cancer patient’s experience. Oncologist. 2013;18(4):381-90.
- Shanafelt TD, Borah BJ, Finnes HD, et al. Impact of ibrutinib and idelalisib on the pharmaceutical cost of treating chronic lymphocytic leukemia at the individual and societal levels. J Oncol Prac. 2015;11(3): 252-258.