New Clinic Tackles Mutations That Increase Risk of Blood Cancers and Heart Disease

Cleveland Clinic Cancer Center’s new CHIP Clinic — the first of its kind in Ohio and one of only a few in the U.S.— will screen and monitor patients with clonal hematopoiesis of indeterminate potential (CHIP): somatic mutations in blood or bone marrow cells that increase the risk of blood cancers and heart disease.

The clinic has been approved by Cleveland Clinic’s Institutional Review Board and will open in early 2020, according to hematologist/oncologist Bhumika Patel, MD, who helped develop the program along with hematologist/oncologist Hetty Carraway, MD, and Jaroslaw Maciejewski, MD, PhD, Chair of Cleveland Clinic Taussig Cancer Institute’s Department of Translational Hematology and Oncology Research.

“In the last five years, there have been several large studies conducted in healthy populations that found mutations associated with aging that we commonly see in myelodysplastic syndrome (MDS) and acute myeloid leukemia patients,” Dr. Patel says. “This has sparked interest in learning more and inspired us to launch the CHIP Clinic.”

“Studying these mutations in our cancer survivorship population will help us improve our understanding of their prevalence as well as the progression of CHIP,” she says. “Additionally, we will be able to better tailor interventions for these patients, including education and preventive care.”

The basics of CHIP

Clonal hematopoiesis (CH) — acquired gene mutations in a population of related myeloid cells — typically involves leukemia-associated genes such as DNMT3A, TET2 or ASXL1, although there may be non-leukemia-associated CH mutations as well.

Detection by next-generation DNA sequencing often is inadvertent, occurring when patients are being evaluated for hematologic or other disorders. However, the presence of a CH variant (usually only a single mutated gene rather than multiple ones) is not definitively determinative of progression to hematologic malignancy. Clinical outcomes of hematopoietic clonality range from asymptomatic apparent normalcy, as seen in the majority of the affected population, to cytopenia, cardiovascular complications and/or overt blood cancers. The dynamics of progression are unclear. CH prevalence is thought to be rare in persons younger than 40 but increases with age, affecting 10% of those older than 70.

CHIP is defined as the presence of a variant allele frequency of ≥ 2% of a leukemia-associated somatic mutation, but with normal peripheral blood count and no evidence of hematologic malignancy. Research shows CHIP is associated with heightened risks of all-cause mortality and hematologic cancer compared to the general population. The increased overall mortality may be due more to heart disease and stroke than to hematologic cancer.

Based on current knowledge about CH, there are no consensus guidelines on screening or monitoring for patients with CHIP.

Multidisciplinary approach

Initially, screening efforts of the CHIP clinic will focus on breast and head and neck cancer patients due to well-established survivorship programs for those malignancies, with plans to eventually expand to all disease groups This will include patients who have already undergone treatment as well as those who are newly diagnosed, to help researchers better understand the origin and evolution of CH mutations and determine whether cancer therapies may affect that process, according to Dr. Patel.

“Our research team will be working closely with clinicians to provide information to our patients and integrate data to study the implications of CH,” Dr. Patel says.

Through the clinic’s work, Dr. Patel and her colleagues aim to better understand the biology of CH, develop clinical trials and establish guidelines to manage individuals with CHIP mutations, with the goal of preventing progression to a hematologic malignancy, such as MDS or leukemia, or cardiovascular disease.

“We hope to prevent the complications associated with CHIP, as well as develop ways to manage these patients and eventually provide targeted interventions,” she says.

The clinic will screen patients with standard blood tests and next-generation sequencing, Dr. Patel explains. “Those who are identified to have a CHIP mutation will have the opportunity to meet with Dr. Carraway, Dr. Maciejewski or myself to discuss their results, further monitoring and to be referred to the appropriate specialists in preventive cardiology to help control risk factors through lifestyle modifications and other interventions,” she says.

Participating patients will receive ongoing blood tests and annual next-generation genetic sequencing. The team intends to screen approximately 50 patients per month initially, but over time hopes to add more, including patients with additional cancer types.

The CHIP Clinic will work closely with Cleveland Clinic Sydell and Arnold Miller Family Heart & Vascular Institute’s Preventative Cardiology and Rehabilitation Section. “The team and their multidisciplinary approach is fantastic,” Dr. Patel notes. “They risk-stratify patients, monitor and offer a variety of resources depending on their needs. This includes smoking cessation, physical fitness, endocrinology and nutrition.”

“This is what makes the CHIP Clinic so valuable,” she says. “We have the opportunity to provide a new level of care and connect patients with the resources they need to improve their health and hopefully mitigate risk factors associated with CHIP.”

Long-term implications

As cancer therapeutics continue to improve and more is learned about CHIP mutations, the clinic also will evolve.

“With more therapeutic options and an aging population of cancer survivors, the CHIP Clinic will continue to grow,” Dr. Patel says. “The clinic will be a platform to improve our understanding of the biology of these mutations and help us be better equipped to provide early interventions to cancer survivors.”

This is just the beginning for the CHIP Clinic, which has the potential to significantly impact not only Cleveland Clinic patients, but wider CHIP research efforts.

“We are going to be evaluating these patients longitudinally,” Dr. Patel notes. “This program is an opportunity to study patients with CHIP in a very broad, multi-dimensional way.”

“And, in the long term, we will have concrete data on the mutations, including the genomic impact of our interventions,” she says. “This will allow us to be at the forefront when it comes to developing guidelines to better manage these patients and their needs.”