Managing Infection Risk in the Era of Cell Therapy

As many cancer treatments evolve from chemotherapy to immune or cell therapies, patients face a different set of vulnerabilities when it comes to infections. To address this situation, oncologists, hematologists, infectious disease physicians and infectious disease pharmacists at Cleveland Clinic’s Cancer Institute work together with their patients to proactively reduce their infection risk.

Background

With traditional chemotherapies, infection concerns tend to be cyclical. These patients are most susceptible to infection when their white blood counts drop. With certain cell therapies, however, a portion of the patient’s B cells and plasma cells remain suppressed for a longer timeframe.

“In some cases, we see viral reactivations that can result in Cytomegalovirus-related infections,” explains Sandra Mazzoni, DO, a hematologist with Cleveland Clinic’s Cancer Institute. “Prevention is the biggest learning point. For our patients post CAR T-cell therapy, for example, we’re encouraging re-vaccination based on a particular schedule as well as the use of immunoglobulins (IVIG). I can’t say enough about IVIG, because we’re seeing that it single-handedly has reduced rates of infection the most.”

As Dr. Mazzoni explains, although some patients with blood cancer may not mount a full response to vaccination, any response is better than no response.

Depending on the patient, their type of cancer, current and future treatment and lifestyle factors, preventative tools may include:

• Antibiotics like sulfamethoxazole/trimethoprim to protect against PJP pneumonia
• Shingles prophylaxis
• Gram-negative antibiotics

Additionally, hand hygiene as well as mask wearing continue to be highly beneficial for warding off illness. Health providers should take additional steps to safeguard patients during and after cancer therapy.

In some centers, this may involve directly admitting a patient to the hospital instead of sending them through a busy emergency room. In other instances, it may mean placing the patient in an individual room while they’re being triaged or ensuring the care team is masked while engaged with the patient.

Educating providers about emerging risks

Raising awareness among primary care, urgent care and other providers is essential, as infection in a patient treated with cancer may present differently than expected. For one thing, lack of a fever does not rule out infection in a patient who is immunocompromised. “After bone marrow transplantation, infections may present with a wide range of symptoms other than fever. Patients may not always mount a typical fever because of immunosuppression. For example, certain fungal infections and urinary tract infections may occur without a fever.

“I tell my patients to recognize their own patterns and if something doesn’t feel right, reach out to your oncologist or hematologist,” says Jessica Lum, MD, an infectious disease physician with Cleveland Clinic

Infectious disease providers encourage other physicians to maintain a low threshold for evaluation when patients develop new symptoms or experience clinical worsening from their baseline. Immunocompromised patients may become ill if they contract infections such as RSV or adenovirus, so staying on top of that is essential. In some cases, if a patient was near someone with influenza, for instance, it may be appropriate to immediately prescribe oseltamivir for prevention.

It can sometimes be more challenging to address infection risk with newer therapies that may have drug interactions. As one example, the AML medication ivosidenib can interfere with certain antifungal treatment.

If a unique clinical scenario like this emerges, caregivers at Cleveland Clinic may consult with a member of the infectious disease team and pharmacy team on the best approach. Additionally, infectious disease, pharmacy and hematology teams developed an antimicrobial protocol to guide Cleveland Clinic providers caring for patients after receiving CAR T-cell therapy.

Personalizing preventative measures

“The preventative recommendations we suggest may depend on the patient’s type of cancer, underlying disease progress, their treatment regimen for their cancer and the next steps for managing their disease and the goals of therapy,” says Dr. Lum. “Management decisions are individualized and depend not only on these factors, but also on the patient’s potential environmental exposure risks and lifestyle, including hobbies, occupational exposures, animal contacts and dietary habits. For example, the infection risk profile is very different in a patient receiving chemo as a bridge therapy versus someone who’s receiving it for many cycles.”

Patient education

Open communication is key in counseling patients about infection risk. “It’s about figuring out what is the patient's day-to-day life right now, what's really important to them and how can we help them balance risks versus safely enjoying their life,” says Dr. Mazzoni. “Particularly with cell therapies, infection is a long-term concern but patients’ mental health really needs to be cared for as well. We need to guide the patient in how to live safely yet balance their mental health so they’re not feeling locked in a bubble.”

As patients recover from a stem cell transplant or cell therapy, a member of the infectious disease team meets with them to learn about them and make individual recommendations based on their needs. Risk mitigation can vary based on many elements, such as:

• Medical history. “I get a detailed history of the patient, including how their recent medication and/or transplant has affected their immune system thus far,” says Dr. Lum.
• Occupation. Those working in health care, law enforcement or in prison systems may consider latent tuberculosis screening, for example.
• Place of residence. Depending on where they live, patients may need to be cautious about inhalation of dust or dirt, particularly if it’s a region where histoplasmosis, valley fever coccidioides or other fungus are prevalent.
• Medications received. The therapies the patient received will determine how soon they can be re-vaccinated.
• Patient’s hobbies and other personal interests. Post-transplant, patients need to take extra precautions when gardening. Additionally, hot tub use is discouraged due to the risk of non-tuberculous mycobacteria.
• Upcoming plans. The timing and destinations of upcoming international travel may warrant additional preventive measures, including travel vaccinations and counseling on safe living practices to reduce the risk of infection
• Diet. The infectious disease team provides guidance on food and water safety and can guide patients on best practices.
• Pets. “In general, having a dog or cat is fine for patients – they’re part of the family – but there are certain things we recommend being careful about, like watching for ticks during warmer weather. We’re less enthusiastic about patients after a stem cell transplant having reptiles due to the risk of salmonella. Chicken coops also put patients at higher risk of fungal infections like histoplasmosis,” says Dr. Lum.
• Sexual lifestyle. “We encourage patients to safely enjoy their relationship but just be open with their provider to avoid any preventative infections,” says Dr. Mazzoni. “I have plenty of patients who are not in monogamous relationships and that’s ok too. It’s all about building trust so that they feel comfortable telling me so that we can find a way to balance what’s important to them while keeping them safe.”

The purpose of the consultation isn’t to dictate to the patients what to do but to understand their wants and needs and how best to recommend safety measures in line with those goals. “Our patients have survived a lot,” says Dr. Lum. “They've gone through tough regimens. They’ve done the hard work and now it’s our job to make sure they can enjoy the benefits of that.”