expert roundtables

Initial Approach to Newly Diagnosed Patients With Chronic Myeloid Leukemia

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

Overview

A number of patient-specific factors aid in fine-tuning the approach to the treatment of patients with newly diagnosed chronic myeloid leukemia (CML). An understanding of the role of molecular response and an awareness of treatment side-effect profiles can help patients to be more engaged and invested in their care.

Q:

What are some of the key points to discuss early on with patients with newly diagnosed CML?

Gabriela S. Hobbs, MD

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

When first meeting with newly diagnosed patients, involving them in their care is key.”

Gabriela S. Hobbs, MD

When first meeting with newly diagnosed patients, involving them in their care is key. This includes helping them to understand their disease and encouraging their active participation so that they can share in the decision making. It is important to introduce the verbiage that we use to discuss the disease, so I will tell them something like, “There’s a term you’re going to hear me say again and again called the Philadelphia chromosome or BCR-ABL, and we use this technique to monitor your CML called polymerase chain reaction or PCR, and we’re going to be following your BCR-ABL with this technique.” 

In addition to introducing CML terminology, it is important to discuss what patients can expect with treatment, including at the beginning of treatment vs later on, in terms of both response and side effects. For instance, some side effects at the beginning of treatment may lessen with time. Other side effects, such as pleural effusions, may be less common but no less important from the perspective of early recognition. Patients should also understand that they will be seen frequently at the beginning of treatment but the pace of the visits should slow as treatment progresses. Providing such guidance is helpful, and I think that it is also critical to be able to spend time with patients to develop good relationships so that you can help them succeed with their treatment. 

When selecting a medication for a newly diagnosed patient, there are several factors to consider, including disease risk, comorbidities, costs, and patient preferences. There are also those goals that are specific to the individual patient and their state in life. For example, achieving a major molecular response that might allow for discontinuation may be important to a young woman who plans to have a family in the future. And, when counseling a young patient who asks about long-term treatment with a tyrosine kinase inhibitor (TKI), I may share that treatment decisions are based on all of the available information at that moment in time. Forever is a long time, and it is likely that the field will change over the next few decades.

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 

“Younger patients with newly diagnosed CML would potentially be on therapy for decades and would therefore benefit the most from a level of response that would allow for treatment discontinuation.”

Neil P. Shah, MD, PhD

My initial approach to newly diagnosed CML is similar to the approach of Dr Hobbs, with an emphasis on patient education early on. I also agree with her general approach to selecting therapy and the importance of patient-specific goals and comorbidities. Regarding the question of when one would consider recommending an initial therapy other than imatinib, there are 3 second-generation agents that are available. These agents do show higher rates of response in patients with newly diagnosed CML, but there are still some individuals who do not respond to the second-generation agents while many respond adequately to imatinib. So, there are a number of additional considerations. We know that all of the TKIs tend to perform better in patients with low Sokal risk disease. Imatinib is highly active and entirely appropriate in the low-risk setting.

Patients with intermediate- and high-risk disease are more likely to achieve deep responses with second-generation drugs. Younger patients with newly diagnosed CML would potentially be on therapy for decades and would therefore benefit the most from a level of response that would allow for treatment discontinuation, and so, a second-generation agent may be indicated. In contrast, imatinib, with its relatively mild toxicity profile, may be fine for an older patient diagnosed with high Sokal risk CML. Therefore, the patient’s age and comorbidities at the time of diagnosis factor into treatment decision making. Patient preferences should also be included in the decision-making process, particularly as they relate to convenience of the treatment regimen and the potential for long-term toxicities.

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

“As my colleagues have detailed, ultimately, there is a great deal of art involved in choosing the right drug and in adjusting the treatment plan along the way."

Mark J. Levis, MD, PhD

To add to the discussion regarding patient age, I think that there are clear differences in how we approach patients who are younger vs patients who are older at the time of CML diagnosis. Compared with a younger patient, an older patient may be on several medications to manage multiple comorbidities, and the initiation of a TKI to treat newly diagnosed CML could interfere with these other drugs. A younger patient, however, can generally start treatment with relative ease.

Regardless of the patient’s age, it is important to discuss with the patient that treatment will be a joint journey with shared decision making. These patients have a leukemia diagnosis and are therefore deeply concerned, so conversations that help them understand all of the key issues can also help them regain a sense of control. During these discussions, I emphasize that it may take several months to find the right drug and the right dose to effectively manage their disease. Patients who are aware of the side-effect profiles of the various drugs and who understand the role of molecular response can be much more engaged and invested in their care. Each patient is different in how they respond to therapy, and there is not a reliable formula that a clinician can follow to reach an optimized treatment plan. As my colleagues have detailed, ultimately, there is a great deal of art involved in choosing the right drug and in adjusting the treatment plan along the way.

References

Chen K-K, Du T-F, Wu K-S, Yang W. First-line treatment strategies for newly diagnosed chronic myeloid leukemia: a network meta-analysis. Cancer Manag Res. 2018;10:3891-3910. doi:10.2147/CMAR.S177566

Gugliotta G, Castagnetti F, Breccia M, et al. Ten-year follow-up of patients with chronic myeloid leukemia treated with nilotinib in first-line: final results of the GIMEMA CML 0307 trial. Blood. 2019;134(suppl 1):4145. doi:10.1182/blood-2019-126163

Hochhaus A, Boquimpani C, Rea D, et al. Efficacy and safety results from ASCEMBL, a multicenter, open-label, phase 3 study of asciminib, a first-in-class STAMP inhibitor, vs bosutinib (BOS) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with ≥2 tyrosine kinase inhibitors (TKIs) [abstract LBA-4]. Abstract presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020.

Hochhaus A, Larson RA, Guilhot F, et al; IRIS Investigators. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376(10):917-927. doi:10.1056/NEJMoa1609324

Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. Am J Hematol. 2018;93(3):442-459. doi:10.1002/ajh.25011

Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic‐phase chronic myeloid leukemia. N Engl J Med. 2010;362(24):2260-2270. doi:10.1056/NEJMoa1002315

Pan P, Wang L, Wang Y, et al. Systematic review and meta-analysis of new-generation tyrosine kinase inhibitors versus imatinib for newly diagnosed chronic myeloid leukemia. Acta Haematol. 2020;143(3):204-216. doi:10.1159/000501537

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