Precision Medicine in the Care of Patients With Leukemia/Lymphoma

The leukemias and lymphomas represent a group of heterogeneous myeloid or lymphoid clonal stem cell disorders with variable clinical presentation, pathological characteristics, prognosis and recommendations for treatment.[1] Recent clinical trials have refined the diagnostic process, established risk-stratified treatment guidelines, introduced novel therapies, and improved supportive care strategies; this has resulted in improvements in response rates, overall survival, disease control, and quality of life for patients.[2] Death rates from lymphoma decreased by 16.85% between 1991 and 2007, and death rates for all types of leukemia combined decreased by 11.86%. Survival trends for chronic myelogenous leukemia (CML) in that same period improved by 18%.[3] The reduction in mortality for CML is attributed to the development of tyrosine kinase inhibitor (TKI) agents that target the BCR-ABL fusion gene, an oncoprotein thought to promote transformation of normal myeloid cells into the abnormal cells of CML.[4] The first FDA-approved TKI agent, imatinib (Gleevec), was approved in 2001. Advances in molecular biology, development of targeted therapies, and refinement of treatment strategies have significantly improved the prognosis for leukemia and lymphoma, yet wide variations exist in survival and response to treatment, based on disease attributes and individual patient characteristics.

The shift from dose-intense standard chemotherapy to therapies targeting specific signaling pathways, molecular targets, or elements of the tumor microenvironment has ushered in the concept of precision medicine.[5] Precision medicine is the application of predictive biomarkers together with consideration of prognostic biomarkers and patient attributes in the selection of therapy, using a personalized life-span approach.[1,6] Applying the concepts of predictive and prognostic indices in risk-adapted treatment selection is expected based on recent scientific discoveries. Selecting treatment based on the general diagnosis of leukemia or lymphoma is no longer acceptable. The selection of therapies based on specific diagnostic criteria adds an element of complexity and variability to therapy for each patient and challenges the oncology professional to maintain a working knowledge of the diagnostic process, which in turn drives treatment selection and, in many cases, evaluation of treatment response.

Most of these diseases are not curable but are highly treatable, with a shift toward a chronic-disease model and primarily outpatient clinical management. The peak incidence for each disease is in patients over the age of 65 years.[1] Given the anticipated increase in incidence and prevalence of these hematologic diseases, the predominance of cases in older adults, and a shift toward a chronic-disease model with clinical monitoring and treatment continuing over many years, familiarity with recent clinical trials data-including risk-adapted treatment selection, monitoring guidelines and management of disease- and treatment-related adverse events-will be essential for optimal management of these diseases.[7] Scientific practicality is perhaps the most important component of precision medicine. This is a term I use to describe the application of clinical trials data to the population at large in a way that allows effective control of the disease for as long as possible with an acceptable level of toxicity.[5] This concept is of particular importance in patients with leukemia and lymphoma who have incurable disease.

Rogers has provided a comprehensive, timely, and clinically relevant overview of targeted therapies used in the management of leukemias and lymphomas, including monoclonal antibodies, radioimmunotherapy, TKIs, histone deacetylase inhibitors, hypomethylating agents, and proteasome inhibitors. These therapies are in large part responsible for the improvement in clinical outcomes in these diseases. They do, however, have unique toxicity profiles that require specific screening, monitoring, and patient and caregiver education to ensure safe and effective treatment. These toxicity profiles may vary for individual agents based on the disease treated and use as a single agent or in combination therapies. Some of the treatment requirements and potential adverse events are unique to these agents. The Rogers article will provide an invaluable clinical tool for oncology professionals involved in the care of patients with leukemia or lymphoma.

Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

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References

1. Kurtin S: Risk analysis in the treatment of hematologic malignancies in the elderly. J Adv Pract Oncol 1(1):19–29, 2010.

2. Kurtin S: Leukemia and myelodysplastic syndromes. In Yarbro CH et al (eds): Cancer Nursing: Principles and Practice, 7th ed. Boston, MA, Jones and Bartlett Publishers, LLC, 2011.

3. Siegel R, Ward E, Brawley O, et al: Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 61(4):212–236, 2011.

4. Kantarjian H, Cortes J: Considerations in the management of patients with Philadelphia chromosome–positive chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy. 29(12):1512–1516, 2011.

5. Kurtin S: Precision medicine: Applying predictive and prognostic indices to risk-adapted treatment selection. The Oncol Nurse April 2012 [In press].

6. Yap TA, Sandhu SK, Workman P, et al: Envisioning the future of early anticancer drug development. Nature Reviews Cancer 10:514–523, 2010.

7. Kurtin S: Managing hematological malignancies: The balancing act. J Adv Pract Oncol 2(suppl 2):5–6, 2011.