Discontinuation of Treatment With TKIs in CML

Panelists: Rafael Bejar, MD, PhD, UCSD; Harry P. Erba, MD, PhD, UAB; Elias J. Jabbour, MD, MD Anderson;
Rami S. Komrokji, MD, Moffitt; Mark J. Levis, MD, PhD, Johns Hopkins; Ruben A. Mesa, MD, Mayo Clinic
Published Online: Friday, January 10, 2014
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The treatment of patients with chronic myelogenous leukemia (CML) changed drastically with the approval of TKIs that target the BCR-ABL fusion gene, effectively transforming CML into a chronic condition in many situations. However, the long-term administration of TKIs to control CML can result in a range of side effects and financial burdens, begging the question of whether or not their administration should ever be stopped.

To address these concerns, the STIM1 and STIM2 trials explored the discontinuation of the TKI imatinib in patients with CML who experienced a sustained deep molecular response (DMR) for more than 2 consecutive years, explains Elias J. Jabbour, MD. In a median 12-month follow up from the STIM2 study, a molecular relapse occurred in 39% of patients. Additionally, all patients were able to achieve a complete molecular remission (CMR) when rechallenged with a TKI, Jabbour notes.

In the STIM trials, the numbers of natural killer (NK) cells were assessed at the time of treatment discontinuation, Jabbour notes. In general, patients with sufficient levels of functional NK cells were less likely to relapse when compared to patients with low levels of dysfunctional cells. These results suggest that NK cell-related immunity to may contribute to CML control after TKI cessation, Jabbour believes. However, more research is needed to discover whether NK cells could be used as a biomarker to predict relapse.

Despite these promising findings, Jabbour cautions that stopping treatment with TKIs should still only be performed within the confines of a clinical trial. Rami S. Komrokji, MD, also reiterates that more research is needed before TKI cessation becomes standard practice.

With the multiple agents now available for CML, another issue that has become common is a premature switch in therapies at the first sign of toxicity, Ruben A. Mesa, MD, says. Every therapy comes with some degree of side effects, it’s important to remember this, before rapidly switching between treatments, Jabbour notes.

In select circumstances, patients may request that treatment be stopped, specifically for female patients wishing to become pregnant. For these patients, Rafael Bejar, MD, PhD, suggests closely monitoring patients for relapse after discontinuation. If needed, treatment with interferon alfa can be utilized, although it is uncommon. For male patients, there is not a need to stop treatment with TKIs, as teratogenic effects related to treatment are unlikely.

View More From This Discussion
Episode 1 Introduction: Treatment Landscape of MDS
Episode 2 Discontinuation of Treatment With TKIs in CML
Episode 3 Frontline Treatment of Chronic Myelogenous Leukemia
Episode 4 Second-Generation Tyrosine Kinase Inhibitors in CML
Episode 5 Treatment Selection for Resistant or Intolerant CML
Episode 6 Hypomethylating Agents in the Treatment of High-Risk MDS
Episode 7 Role of Genetic Testing in Myelodysplastic Syndromes
Episode 8 Defining and Predicting Response to HMAs in MDS
Episode 9 Treatment of MDS Refractory to Hypomethylating Agent
Episode 10 Current and Future Treatment Landscape for MDS
Episode 11 Novel Agents and Treatment Strategies in MDS
Episode 12 Oral Azacitidine and Lenalidomide Combinations in MDS
Episode 13 Final Thoughts on Clinical Advances in MDS and CML
Expert Panelists
Harry Erba Moderator

Harry P. Erba, MD, PhD

Professor of Internal Medicine
Director of Hematologic Malignancy Program
University of Alabama
Birmingham, Alabama

Mark J. Levis, MD, PhD

Director, Adult Leukemia Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland

Elias J. Jabbour, MD

Associate Professor,
Department of Leukemia,
Division of Cancer Medicine,
MD Anderson Cancer Center, Houston, Texas

Rami S. Komrokji, MD

Clinical Director, Associate Member, Department of Malignant Hematology
H Lee Moffitt Cancer Center
Tampa, Florida

Ruben A. Mesa, MD

Chair, Division of Hematology
& Medical Oncology, Mayo Clinic, Scottsdale, Arizona

Rafael Bejar, MD, PhD

Assistant Professor of Medicine, Division of Hematology-Oncology
University of California, San Diego, La Jolla, California
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