expert roundtables

Chronic Myeloid Leukemia: Current Recommendations for Treatment and Monitoring

by Gabriela S. Hobbs, MD; Mark J. Levis, MD, PhD; and Neil P. Shah, MD, PhD

Overview

Current guidelines identify the goals of chronic myeloid leukemia (CML) treatment, with an emphasis on the achievement of a stable deep molecular response, allowing for the consideration of the discontinuation of tyrosine kinase inhibitor (TKI) therapy. Here, experts discuss their approaches to treating and monitoring CML in view of these guidelines.

Q:

How do you incorporate CML treatment and monitoring recommendations in your practice?

Neil P. Shah, MD, PhD

Edward S. Ageno Distinguished Professorship in Hematology/Oncology
Professor, Department of Medicine
Program Leader, Hematopoietic Malignancies Program
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, CA 

“The majority of patients who are adherent to treatment with TKIs have excellent outcomes. For these individuals, the focus in my clinic quickly shifts to trying to preserve QOL and reduce those bothersome toxicities."

Neil P. Shah, MD, PhD

We are fortunate that there are now several highly effective treatment options for CML. The goal of CML treatment is to not only improve rates of remission but also to ensure a good quality of life (QOL). The majority of patients who are adherent to treatment with TKIs have excellent outcomes. For these individuals, the focus in my clinic quickly shifts to trying to preserve QOL and reduce those bothersome toxicities. Side effects in some patients could be possibly ameliorated or substantially mitigated by dose reduction. There is a substantial amount of collective experience among CML experts to suggest that dose reductions are relatively safe in many cases, as long as the patient’s CML is being monitored and the patient is being assessed regularly for improvements in QOL. In the future, we will likely see dose modifications with CML therapies occurring more frequently to support the QOL end points that are most important to patients. Ideally, we will investigate the effect of dose modifications on treatment success through clinical trials.

The monitoring of treatment response has improved with the development of polymerase chain reaction–based molecular monitoring. Despite the usefulness of contemporary guidelines, there is some variability among clinicians in the optimal frequency of response monitoring. Following treatment initiation, I believe that an initial monitoring interval of every 3 months is appropriate. On the one hand, one does not want to be too relaxed about monitoring; on the other hand, monitoring more frequently may lead to micromanagement and unnecessary concern and alarm, as random fluctuations can occur. Ultimately, I think that following available guidelines makes good sense.

It is very important to monitor treatment adherence and treatment response, given the transformative nature of available therapies. Some patients who go into remission stop taking their medications and ultimately develop splenomegaly and leukocytosis. It is often difficult to recapture that same level of the initial response, and these patients become at risk for the development of secondary resistance and progression to advanced-phase CML, which can be difficult to manage medically.

Mark J. Levis, MD, PhD

Director, Adult Leukemia Service
Co-Division Director, Hematologic Malignancies
Professor of Oncology
The Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins University
Baltimore, MD

“When I first meet with a newly diagnosed patient, I make sure that they understand the alarming risks associated with CML, including early death. I then stress the importance of medication adherence."

Mark J. Levis, MD, PhD

Having lived through a time when CML was not as easily managed as it is today, including a period when patients were expected to eventually die from the disease unless they received a bone marrow transplant, I find that some clinicians have swung a little too far the other way in communicating risk, due to the effective treatment options that are now available (ie, the TKIs).

In my opinion, the big issue relates to medication adherence. When I first meet with a newly diagnosed patient, I make sure that they understand the alarming risks associated with CML, including early death. I then stress the importance of medication adherence. I do this because I have seen so much tragedy when patients are not adherent because they do not understand how serious the disease can be.

Side effects are a major contributor to nonadherence. When we are dealing with side effects, dose adjustment may be necessary. If the clinician has a “handle” on the molecular response, the dose can often be adjusted with confidence, as long as the patient is being monitored per the recommendations. In the future, I look forward to seeing emerging data on the long-term side effects of TKIs. It will be interesting to see how these data will influence practice recommendations moving forward.

Gabriela S. Hobbs, MD

Assistant Professor, Medicine
Harvard Medical School
Clinical Director, Leukemia
Massachusetts General Hospital
Boston, MA

“Following treatment initiation, monitoring is important. Fortunately, there are excellent CML guidelines available that can help providers make sure that a patient is being well monitored and treated."

Gabriela S. Hobbs, MD

We are fortunate in that 4 drugs are currently approved for first-line use in CML, and they are all excellent in helping patients achieve remission. Although TKIs are the standard of care, initially choosing the right TKI for each patient requires careful consideration. The choice of TKI should be based on the patient’s comorbidities, other medical issues, risk score at diagnosis, and insurance coverage.  

Following treatment initiation, monitoring is important. Fortunately, there are excellent CML guidelines available, including those from the National Comprehensive Cancer Network and the European LeukemiaNet, that can help providers make sure that a patient is being well monitored and treated. Although patients with CML may not always look ill, monitoring is essential to assess for early molecular remissions. Importantly, when individuals with CML are intermixed in a clinic of patients receiving active chemotherapy, one may be “fooled” into thinking that they are the healthiest. This, on top of a lack of resources or the busyness of a clinic, can result in guidelines not being followed as closely as they should.

References

An X, Tiwari AK, Sun Y, Ding P-R, Ashby CR Jr, Chen Z-S. BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review. Leuk Res. 2010;34(10):1255-1268. doi:10.1016/j.leukres.2010.04.016

Bower H, Björkholm M, Dickman PW, Höglund M, Lambert PC, Andersson TM-L. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol. 2016;34(24):2851-2857. doi:10.1200/JCO.2015.66.2866

Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966-984. doi:10.1038/s41375-020-0776-2

Hughes T, Deininger M, Hochhaus A, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108(1):28-37. doi:10.1182/blood-2006-01-0092

Soverini S, De Benedittis C, Mancini M, Martinelli G. Best practices in chronic myeloid leukemia monitoring and management. Oncologist. 2016;21(5):626-633. doi:10.1634/theoncologist.2015-0337

More in Chronic Myeloid Leukemia

Thumb

Chronic Myeloid Leukemia

Expert Perspectives in Chronic Myeloid Leukemia to Cover Key Topics in Chronic Myeloid Leukemia Treatment

Expert Perspectives

Expert Perspectives delivers health care providers with insights from key thought leaders on the latest advancements and current practices in medic...READ MORE

Thumb

Chronic Myeloid Leukemia

Next-Generation Sequencing–Detectable Mutations in Chronic Myeloid Leukemia

Clinical Topic Updates by Gabriela S. Hobbs, MD

Although upfront testing with next-generation sequencing (NGS) for BCR-ABL1 kinase domain mutations is not currently standard, the science of mutat...READ MORE

Thumb

Chronic Myeloid Leukemia

COVID-19 and Impacts in Patients With Chronic Myeloid Leukemia

Patient Care Perspectives by Gabriela S. Hobbs, MD

The COVID-19 pandemic has challenged clinical care, particularly for patients with chronic myeloid leukemia (CML). The increased uptake of telemedi...READ MORE

More In Oncology

cGVHD

Chronic Graft-versus-Host Disease: Biomarkers, Mediators, and Druggable Targets

Clinical Topic Updates by David Miklos, MD, PhD

cGVHD

Evolving Transplant Technology and Chronic Graft-versus-Host Disease

Patient Care Perspectives by Edmund K. Waller, MD, PhD, FACP

cGVHD

Advancements in the Management of Chronic Graft-versus-Host Disease

Expert Roundtables by Corey Cutler, MD, MPH, FRCPC; David Miklos, MD, PhD; and Edmund K. Waller, MD, PhD, FACP