Comorbidity: Treating the Whole Patient

TERESA ALTEMEYER OF INDIANAPOLIS HAD A CONCERN about her breast cancer treatment. After being diagnosed with stage I breast cancer in 2018, Altemeyer, then 68, was treated with surgery and radiation. She was prescribed the aromatase inhibitor letrozole after treatment to suppress her body’s production of estrogen, which fuels many cases of breast cancer. The treatment plan was standard for someone with Altemeyer’s diagnosis, and she had every reason to believe the medicine would lower her risk of the disease returning. But breast cancer wasn’t her only concern.

Just a few days after her cancer diagnosis, Altemeyer was diagnosed with Parkinson’s disease. In the course of her cancer treatment, she read about new research suggesting that estrogen helped mitigate the effects of Parkinson’s disease. She wanted to talk to her oncologist about switching from letrozole to a medicine that could block cancer from using the estrogen in her body, rather than deprive her body of estrogen and its possible benefits in managing Parkinson’s. The oncologist spoke to Altemeyer’s movement disorder specialist, and they decided to make the change.

The particulars of Altemeyer’s case are unique, but having two or more diseases at the same time is common, especially in older cancer patients. An analysis of Medicare beneficiaries with cancer found that four out of 10 have at least one other condition, and 15% have at least two. The term for this state is “comorbidity,” though when talking about cancer or other diseases, it’s common to hear second or third conditions referred to as “comorbidities.” 

“When a patient is diagnosed with cancer and they first walk in the door, this may not be their first interaction and should not be their first interaction with the medical system,” says Andrew H. Lipsky, a hematologist-oncologist at Columbia University Medical Center in New York City. “They have been living their life; they have been seen by a primary care doctor.”

Lipsky says many common conditions develop as people grow older—including high blood pressure, coronary artery disease and diabetes—and they are often present when a person is diagnosed with cancer.

Comorbidity has been associated with lower cancer survival and can affect a cancer treatment plan.  The diseases can interact, and treatments for cancer can also interact with other diseases and other medicines. For example, anthracycline-based chemotherapy, radiation to the chest and HER2-targeted therapy, such as Herceptin (trastuzumab), can affect the heart and worsen existing heart problems.

“Some patients, they can already have a lot on their plate medically, and that can add not only an additional source of stress but an additional degree of medical complexity when choosing a treatment regimen for that patient,” Lipsky says.

Managing Comorbidity

The specifics of a diagnosis are important in determining what organs are affected by your conditions, treatment side effects and interactions with other medicines. These factors impact whether you need to consider changing your treatment plan. For most cancers, possible effects from comorbidities are not described in treatment guidelines, and oncologists have to work with other members of the care team to determine the best way to balance treatment for cancer and other health concerns.

According to Alexey Danilov, a hematologist-oncologist at City of Hope Comprehensive Cancer Center in Duarte, California, early collaboration between doctors is key to effectively managing comorbidity.

“When we assess a patient, it’s always important to have all the information from the primary care physician,” says Danilov. The primary care physician will have more information about a new patient’s medical history—what conditions they have, how long they have had them, how well they have been managed and, importantly, what medicines they are currently taking for the conditions. 

With diverse new options for treating cancer with chemotherapy, immunotherapy and targeted therapy, doctors have a lot of options, Danilov says. “But, also, that means that there is a lot of complexity in terms of the metabolism of these drugs.” Getting a picture of all the medicines a person may be taking and having that information available for different providers is important to prevent harmful drug interactions. Danilov says pharmacists, who have expertise in the interactions between drugs, provide another layer of protection in making sure treatments aren’t given that would lessen the efficacy of a therapy or harm the patient.

Together, the medical team can decide if treatment changes should be made. These can include dose adjustments to cancer medicines, but Danilov says it’s also common to ask the primary care physician or a specialist if it is possible to change the dose of the medicine for the comorbidity or switch to another medicine that doesn’t have the same interaction with the cancer medicine.

“Typically, other specialists are very willing to work with us and make adjustments, because with cancer treatment, often it’s a question of life and death,” Danilov says.

In other patients, it’s a matter of watching closely how the addition of a cancer treatment affects the health conditions already present. This may involve extra tests as a person is treated, but if the different health care providers are in contact, this can be arranged in a way that isn’t overly burdensome to the patient.

Joan Godfrey, 51, from Yonkers, New York, had diabetes for almost 20 years when she was diagnosed with chronic lymphocytic leukemia (CLL) in 2019. Prior to her CLL diagnosis, she had gone to multiple doctors and been offered antibiotics, but her symptoms only worsened. As time passed, she had more trouble living her daily life and couldn’t walk for five minutes without stopping for a rest. One day, without warning, she lost her sight for a few minutes, and then she knew she needed more care. After another doctor diagnosed her with CLL, Godfrey saw Lipsky, who admitted her to the hospital immediately.

“He said to my husband, ‘If you let your wife walk through that door tonight, she’s going to die,’” Godfrey says about the decision to be admitted rather than returning home.

As Godfrey was treated for CLL with Calquence (acalabrutinib), Lipsky and her primary care physician, whom she sees for diabetes and blood pressure, wanted to keep an eye on her blood sugar as treatment progressed. To the relief of Godfrey, who does not like getting her blood drawn, Lipsky often checks with her primary care physician when he needs to have blood drawn. That way, they can collect the blood from one draw instead of making her report for separate tests.

Measuring Comorbidities

One study of patients with CLL found the effect of comorbidities to be similar to having multiple chromosomal abnormalities, known as a complex karyotype, which studies have shown predict shorter survival. Because of the potential of comorbidity to worsen cancer outcomes, researchers have tried to examine the effects of comorbidities on cancer outcomes in CLL patients and develop new tools that collect meaningful information on a patient’s comorbidities. That data can be used to guide treatment decisions for all of a patient’s diseases and help researchers better understand the relationship between CLL and other conditions.

The cumulative illness rating scale, commonly known as CIRS, is one tool researchers use to measure comorbidities in clinical trials, but Danilov says this system, in which 14 organ systems are examined and rated on severity of impairment, is not practical for regular cancer care at the clinic. Danilov is part of a team studying a tool called the CLL-comorbidity index, or CLL-CI, which could be more practical for clinical use and provide more directly relevant information on patients with CLL and other blood cancers. CLL-CI focuses on conditions in three systems of the body that have been associated with worse survival in CLL: the endocrine system (which includes diabetes), the vascular system and the gastrointestinal system. The goal of tools like this one is to provide standard, evidence-based measures that can easily be incorporated into clinical trials and clinical care, without a time-consuming assessment.

In a study of patients in the Danish National CLL Register published April 26, 2022, in Blood Advances, Danilov and his colleagues found that the CLL-CI categories of low, intermediate and high risk were associated with the time it took for patients to progress to the next line of therapy and overall patient survival. The length of time to the next line of treatment and overall survival decreased as the CLL-CI risk score increased.

In current practice for most patients, Lipsky says, doctors rely on overall impressions of a patient’s health, the doctors’ own knowledge, and the resources available outlining potential drug interactions and side effects associated with each medicine.

“The first thing [I think] when I look at somebody with comorbidities is, ‘Is this really affecting their activities of daily living in a way where what we call their performance status is different?’” Lipsky says. Performance status is a common way of evaluating the fitness of patients and understanding if they can perform regular tasks such as driving, doing light housekeeping and generally being up and active. Understanding performance status could guide what treatment a doctor thinks someone can tolerate and what other support a patient may need.

While many people come in knowing their pre-existing conditions, some patients may not be getting sufficient treatment for those health problems. Others may learn they have another condition while they are seeking care for their cancer, Lipsky says. He adds that it helps to address these other concerns before starting cancer treatment. This may include getting an accurate diagnosis, changing treatment in order to better control conditions such as hypertension and diabetes, or receiving routine care such as vaccinations before starting cancer treatment.

Putting Together the Pieces

When doctors collaborate, the experience for the patient can be reassuring, as Altemeyer found when getting care at Indiana University Health in Indianapolis. “I’ve kept all my doctors, including my general practitioner, who’s an internist, all within the same umbrella,” Altemeyer says. “And that’s paid off, that’s really made a difference.”

Altemeyer, who was diagnosed with CLL in 2009 before her diagnoses for breast cancer and Parkinson’s disease in 2018, has had plenty of interactions with the health care system and received care from different departments, including for infections related to CLL treatment and heart problems associated with chemotherapy. She says going to a large cancer center has given her access to clinical trials and connected her with specialists for her comorbidities. Throughout treatment, her hematologist, oncologist, primary care physician and other health care providers shared information about her case and made sure she got care that accounted for the different diseases and treatments.

That is not the case for everyone. Not all patients want to or are able to get all facets of their care from one health system. Lipsky says this can present challenges, which can include getting the needed information to all providers if the records at each office capture only part of the picture. In these cases, it is important for the patient to provide information on their case, especially when seeing a new doctor. When Lipsky sees a new patient with existing problems, he will try to get a sense of their medical history. What are they being seen for? Is the current medicine keeping the disease under control, and how long has that been the case? Does the patient take their own measurements, for example a blood pressure diary for people with hypertension? And, importantly, what medicines are they currently taking?

“From a doctor’s perspective, when a patient comes in and has an up-to-date list of all of their medications and knows exactly what they’re taking … that gives us a lot of confidence,” Lipsky says.

Patients should expect their doctors to directly address coordination of their care, Lipsky says, and should feel comfortable asking their oncologist to reach out to other providers to resolve any questions. He also encourages patients to remind their doctors of other conditions or medications whenever they change treatment.

“Asking those questions is never a bad idea on the patient front,” Lipsky says.

Learning More About Comorbidity

Clinical trials are an important path for understanding how cancer treatment works, and understanding more about comorbidities starts there. Danilov says that despite recent progress, younger and healthier people are still overrepresented in clinical trials. He says new efforts are being made to get more people who are older and have comorbidities in clinical trials to learn how they fare in treatment.

One example Danilov points to is the SWOG Cancer Research Network, which is currently recruiting patients for a trial studying a combination treatment in diffuse large B-cell lymphoma in patients age 75 or older. The results of the trial will offer insight on patients who, due to their age, are more prone to comorbidity and have not been well represented in drug approval trials. Since older adults are often missing from studies, researchers don’t know if these patients are getting the same benefit from treatment as younger patients with fewer health complications.

“[This trial] is trying to investigate that question by focusing on an older patient population, who tends to have comorbidity,” Danilov says. He stresses the need to have data on how older patients respond to treatment and what adjustments they may need based on their overall health.

Tools used to formalize the understanding of comorbidity may play an increasing role in the care of patients going forward. Lipsky says that with more data, a tool like the CLL-CI, if approved for clinical use, would help clinicians gain access to clear, evidence-based guidance instead of relying on their own judgment, especially in patients with multiple comorbidities.

Additionally, Lipsky says the development of new medicines offers more tools for doctors to use when managing comorbidity. In hematology and for CLL specifically, he says, there are more choices for treatment now than were available a decade ago. “We have many options for regimens to place patients on, and that give us a significant degree of flexibility in tailoring the therapy to both the patient’s preferences with regard to meaningful quality of life and with regard to facilitating the management of their preexisting conditions.”

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