Looking Beyond Overall Survival in Chronic Myeloid Leukemia

Christin Melton, ELS
Published: Thursday, Aug 30, 2018
 Harry Erba, MD, PhD
Harry Erba, MD, PhD
Chronic myeloid leukemia (CML) is one of the great success stories in anticancer therapy. The introduction of tyrosine kinase inhibitors (TKIs) transformed CML from a life-threatening disease to a chronic one for most patients. Although CML remains incurable without a stem cell transplant, the life expectancy for a patient with newly diagnosed disease today approaches that of the general population.1 The result, said Harry P. Erba, MD, PhD, moderator of an OncLive Peer Exchange® panel on current strategies for managing CML, is that the prevalence of CML is rising. One study estimated the prevalence of CML at 70,000 in 2010 and predicted it would increase to 112,000 in 2020, with further increases every decade thereafter before peaking at 181,000 in 2050.2

For a small subset of patients with CML, TKIs are ineffective or intolerable, whereas patients for whom TKIs are effective have historically been faced with the prospect of lifelong therapy. As investigators continue to look for ways to improve outcomes for the growing number of patients with CML, the primary goal has shifted from improving overall survival (OS) to helping patients achieve treatment-free remission (TFR). During the 90-minute OncLive Peer Exchange® panel, Erba and panelists Michael J. Mauro, MD, and Jorge E. Cortes, MD, discussed how new data on TFR and updated guidelines for monitoring patients have influenced their approach in the clinic.

Figure 1. Clinically Relevant Thresholds of BCR-ABL16

Clinically Relevant Thresholds of BCR-ABL1

Optimizing Outcomes With Proper Monitoring

Cortes started the discussion of monitoring by noting that although “close monitoring is critical to optimize benefits [of TKI therapy],”3 only 30% of patients with CML in the United States receive molecular monitoring at the appropriate intervals after starting a first-line TKI. He said failure to monitor patients appropriately prevents clinicians from identifying patients who respond poorly to the initial TKI while time remains to affect outcomes.

The panel agreed that real-time quantitative polymerase chain reaction (qPCR) for BCR-ABL1 transcript levels and bone marrow cytogenetic testing is standard for assessing treatment response and should be measured at diagnosis to provide a baseline comparison.4,5 Cortes said recommendations from the European LeukemiaNet (ELN), the National Comprehensive Cancer Network (NCCN), and other major organizations for subsequent monitoring of BCR-ABL1 transcript levels once patients start TKI therapy are similar: every 3 months until the patient achieves a stable major molecular response (MMR) and every 3 to 6 months thereafter.4,5 He said, at a minimum, every patient should have BCR-ABL1 transcript levels measured at 3, 6, 12, and 18 months after starting a TKI. “I think once a patient has a very stable MMR, every 6 months is fine,” Cortes said.

Erba noted there has been a shift in how molecular response (MR) is measured. Today BCR-ABL1 levels are reported using International Scale (IS) percentages, which correspond with the log reduction in BCR-ABL1 from baseline (Figure 1).6 MR is expressed as BCR-ABL1% on a log scale, where 10%, 1%, 0.1%, 0.01%, 0.0032%, and 0.001% correspond to a decrease of 1, 2, 3, 4, 4.5, and 5 logs, respectively, below the standard baseline that was used in the study. Using the IS, ELN defines an MMR as a BCR-ABL1 expression of ≤0.1% (MR3.0 or better) and a deep MR as MR4.0 or MR4.5 (BCR/ABL1 expression ≤0.0032%).4 Erba explained that NCCN and ELN monitoring recommendations were based on findings from a retrospective study of 282 patients with CML treated with imatinib (Gleevec) between 2000 and 2010 that showed “the BCR-ABL1 to ABL ratio at 3 months was informative regarding progression- free survival [PFS] and OS.”7 The 8-year OS and PFS rates for patients who had a BCR-ABL1 transcript level above or below 9.84% were almost identical: 93.3% for patients with a level ≤9.84% versus 56.9% for patients with a level >9.84% (P <.001 for both comparisons).7

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Online CME Activities
TitleExpiration DateCME Credits
Cancer Summaries and Commentaries™: Update from Atlanta: Advances in the Treatment of Chronic Lymphocytic LeukemiaFeb 28, 20190.5
Year in Review™: Reflecting on Recent Evidence for the Treatment of Hematologic MalignanciesFeb 28, 20192.0
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