Patient Compliance is Crucial

Another management challenge with CML is patient compliance with TKI-dosing schedules. “We know the people who don’t take the damned pills don’t do well,” he said. Missing even just 2 pills a month can cut survival time.

Communicating the importance of compliance to patients is “extremely important,” said Dr Medeiros. Compliance and its survival implications should be discussed with patients with CML at “every visit,” he told Cancer Therapy Advisor. Dr Lipton draws how compliance affects survival curves on his patients’ exam room tables.

The causes of noncompliance vary:5 side effects are one big factor and patient copays are another.6

Older patients frequently take several different medications, and drug interactions can result in more side effects, Dr Lipton noted. Patients don’t always report low-grade adverse events, even when they discourage compliance.

Avoidance is another problem. “Some people just don’t want to face their disease,” he added. “Younger males sometimes think they can get away with it, that they’re immortal. There’s a personality factor. Some look at pill, and they are feeling well, and the only thing that reminds them they are sick is that pill.”

Online support groups are important resources for patients, but online misinformation can be dangerous.

“Unfortunately, there is ‘literature’ on the web out there: people giving advice about taking drug holidays, or taking half-doses, and patients listen to this stuff. There’s a lot of misinformation, both on blogs and discussion boards.”

It is important to communicate to patients that untested herbal therapies like St. John’s Wort, as well as some dietary habits, can affect TKI pharmacology.

“There are TKI interactions with certain foods—fruits, primarily—that we tell a patient not to eat: grapefruit, pomegranate, and several others, because they all affect drug metabolism and toxicity,” Dr Lipton said. “Some people take pomegranate juice daily because they’ve read it has health benefits.”

Multiple dietary supplements and polypharmacy could conspire to diminish the effectiveness of TKI treatment, particularly among elderly patients. “We just don’t know,” Dr Lipton said. “The more you throw into the mix, the more likely there will be an effect.”

References

  1. Yun S, Vincelette ND, Segar JM, Dong Y, Shen, Y, Kim DW, et al. Comparative effectiveness of newer tyrosine kinase inhibitors versus imatinib in the first-line treatment of chronic-phase chronic myeloid leukemia across risk groups: a systematic review and meta-analysis of eight randomized trials [published online ahead of print 2016]. Clin Lymphoma Myeloma Leuk.doi: 10.1016/j.clml.2016.03.003.
  2. Jabbour E, Kantarjian H, Cortes J. Use of second- and third-generation tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia: an evolving treatment paradigm. Clin Lymphoma Myeloma Leuk. 2015;15(6):323-334.
  3. Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre R, Paquette CR, Chuah FE, et al. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013;369:1783-1796.
  4. Lipton JH, Chuah C, Guerci-Bresler A, Rosti G, Simpson D, Assouline S, et al. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukemia: an international, randomised, open-label, phase-3 trial. Lancet Oncol. 2016;17:612-621. doi: 10.1016/S1470-2045(16)00080-2.
  5. Jabbour EJ, Kantarjian H, Eliasson L, Cornelison AM, Marin D. Patient adherence to tyrosine kinase inhibitor therapy in chronic myeloid leukemia. Am J Hematol. 2012;87(7):687-691.
  6. Dusetzina SB, Winn AN, Abel GA, Huskamp HA, Keating NL, et al. Cost sharing and adherence to tyrosine kinase inhibitors for patients with chronic myeloid leukemia. J Clin Oncol. 2014;32(4):306-311.