Experts Emphasize Importance of Preventing Progression in CML

Published: Friday, Jan 29, 2016
Jorge E. Cortes, MD

Jorge E. Cortes, MD

Early diagnosis and early commencement of the most effective treatment available are essential in managing patients with chronic myeloid leukemia (CML), particularly since therapeutic options have expanded and testing technology has advanced.

Those were among the key take-home messages that CML experts conveyed during a recent OncLive Peer Exchange® roundtable entitled “Expert Perspectives on the Management of Chronic Myeloid Leukemia.”

The panel members were mindful of the advancements that have taken place in the CML field in the 15 years since the FDA approved imatinib (Gleevec) for the treatment of patients with Philadelphia chromosome-positive disease in 2001. Now, there are many nuanced treatment questions including the choice of frontline tyrosine kinase inhibitor (TKI) therapy, when to switch agents, and how best to monitor patients.

“The use of tyrosine kinase inhibitors targeting the BCRABL protein is the hallmark of therapy for patients with chronic myeloid leukemia and, as you know, it has transformed this disease from a life-threatening to a chronic one for most patients,” said moderator Jorge E. Cortes, MD. “We continue to refine our approaches to monitoring of CML and treatment of resistance to further improve outcomes for our patients.”

Choosing Upfront TKI Therapy

The panelists agreed that getting patients started on therapy is vital to outcomes. “The sooner they start on definitive treatment, the sooner they’ll reach their treatment milestones, and this can have an impact on their overall survival,” said Kevin Kelly, MD, PhD.

To obtain baseline readings, Harry P. Erba, MD, PhD always orders three assays with new patients: chromosome analysis, FISH testing, and PCR testing, and then orders each test every 3 months. Do not rely on PCR alone, cautions Javier Pinilla-Ibarz, MD, PhD, since “some patients are diagnosed with false-positive low PCR levels.” As to next-generation sequencing, it is not quite ready for use in the clinic, said Pinilla-Ibarz. Performing a baseline bone marrow assessment at the time of diagnosis is “mandatory,” noted Cortes.

Kelly, MD, PhD

Kevin Kelly, MD, PhD

The most important goal of therapy “is the prevention of progression to accelerated phase and blast crisis,” stressed Erba. “It’s really important for the community oncologist to know that when we’re talking about progression, we’re not talking about losing a response and the white count goes up again.”

Rather, Erba said, “progression means that the biology of the disease has changed. The outcome of these patients is worse. Their survival is worse. They’re facing decisions about allogeneic transplant in that position, and when patients progress to accelerated phase or blast crisis, their median survival is about 10 months, So prevention of progression becomes the most important goal in my book, and treating patients with an agent that they can tolerate to do that is important.” Two large randomized controlled trials have shown that second-generation TKIs have fewer progressions to accelerated- or blast-phase disease compared with imatinib.

In the ENESTnd trial, nilotinib (Tasigna) demonstrated a significantly lower probability of progression than imatinib among patients newly diagnosed with CML in chronic phase after a 3-year follow-up.1

In the DASISION trial, dasatinib (Sprycel) delivered faster and deeper responses than imatinib after a minimum follow-up of 3 years.2 The median time to complete cytogenetic response was 3 months with dasatinib compared with 6 months for imatinib, and the proportion of patients with BCR-ABL transcript levels ≤10% was higher in the dasatinib arm.2

Harry P. Erba, MD, PhD

Harry P. Erba, MD, PhD

“All three drugs are very effective, but there is a slight benefit to the second-generation drugs,” said Kelly, noting that the newer drugs are “slightly better tolerated” compared with imatinib. He said his choice of TKI is also influenced by the patient’s comorbidities. He takes the time to sit with each patient and “have a discussion, very much a two-way street, and I assess the comorbidities.”

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