Novel Oral TKI in Chronic Leukemia Requires Genetic Testing, Adherence to Therapy

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TKIs for chronic lymphocytic leukemia require not only long-term with oral medications but also prognostic genetic testing.
TKIs for chronic lymphocytic leukemia require not only long-term with oral medications but also prognostic genetic testing.

CHICAGO--Translating clinical findings from studies of novel agents such as the tyrosine kinase inhibitors (TKIs) to a “real world” chronic lymphocytic leukemia (CLL) population requires not only that patients comply long-term with oral medications but that those treated in United States practices consistently receive prognostic genetic testing, a poster discussant told attendees at the 2015 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL.

This requires an understanding of what drives compliance, such as the cost of agents or their toxicities, because studies have shown that patients who are more compliant with therapy have better outcomes, said Charalambos Andreadis, MD, MSCE, of the University of California, San Francisco in San Francisco, CA, as well as understanding patterns of CLL management.

Dr. Andreadis put into context the results of three poster presentations, two on the TKIs idelalisib and ibrutinib, and the third on prognostic testing patterns in patients with CLL treated in United States practices from the Connect® CLL Registry.

The “menu for CLL therapy [in] 2015,” he said, comprises three columns: “choose your chemo” (purine nucleoside analogues [PNAs], bendamustine, cyclophosphamide, chlorambucil), “add your antibody” (rituximab, ofatumumab, obinutuzumab, alemtuzumab), and “biologics” (ibrutinib, idelalisib, lenalidomide).

In the Barrientos et al idelalisib study,1 Dr. Andreadis said durable responses were observed in the majority of patients across established risk groups. The agent was relatively well tolerated, with few serious adverse events (AEs), and combines well with chemo/immunotherapy, especially for extended treatment duration.

Mean dose intensity in the Barr et al ibrutinib study,2 which examined dose adherence and baseline exposure, was 94.8% (median 99.6%).

However, 30% of patients missed 8 or more consecutive days of ibrutinib treatment, with an associated lower progression-free survival.

“This is expected but concerning,” said Dr. Andreadis, who added that “persistence and adherence issues will be magnified in the real world.” He advised attendees to keep this in mind for nonresponders or early progressors.

Oral medication compliance has three parts: initiation, or filling a prescription/starting to take a medication; persistence, or continuing medication for the prescribed duration; and adherence, or taking the prescribed amount of pills/doses.

Factors that affect compliance are the patient (age, ethnicity, socioeconomics, beliefs, support), therapy (duration, dosing, side effects, taste, route, cost), disease (symptoms and severity), and the health care system (accessibility, visit schedule, provider relationship).

Not surprisingly, he said, in the Mato et al study,3 low rates of FISH and IgVH testing were found in a largely community-based registry. Both the CLL International Working Group and the National Comprehensive Cancer Network guidelines recommend testing for prognosis, but not as “essential.”

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Results from the registry showed that an academic site—compared with a community/government site—was more likely to order FISH. The research also found that the community/government site was more likely to order the test for white patients compared with patients of any other race patients, for those younger than 75 years of age, and for patients with RAI stage 2 or higher compared with RAI stage 1.

This study points to the need to design better prospective trials that incorporate FISH and IgVH testing as predictive, not just prognostic, biomarkers.

“With the plethora of options, we need data to help us choose, combine, and sequence therapies,” Dr. Andreadis concluded, especially since “these are the key biomarkers to define the need for stem cell transplant in this era.”

References

  1. Barrientos JC, Coutre S, De Vos S, et al. Long-term follow-up of a phase Ib trial of idelalisib (IDELA) in combination with chemoimmunotherapy (CIT) in patients (pts) with relapsed/refractory (R/R) CLL including pts with del17p/TP53 mutation. J Clin Oncol. 2015;33:(suppl; abstr 7011).
  2. Barr PM, Brown JR, Hillmen P, et al. Dose adherence and baseline exposure analysis of the ibrutinib 420 mg dose administered to patients with previously treated chronic lymphocytic leukemia (CLL). J Clin Oncol. 2015;33:(suppl; abstr 7012).
  3. Mato A, Flowers C, Farber CM, et al. Prognostic testing patterns in CLL pts treated in U.S. practices from the Connect CLL registry. J Clin Oncol. 2015;33:(suppl; abstr 7013).

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