The Who, What, and When of Managing Adverse Events

Dwight C. Macero, MS, PA-C
Mr. Macero is an instructor in the Blood Cancer and Bone Marrow Transplant Program at the University of Colorado Cancer Center.

In this edition, Dwight C. Macero, MS, PA-C, discusses the role that advanced practice providers play in managing the side effects of hematologic treatments.


Therapies to treat hematologic malignancies (including cytotoxic chemotherapies, targeted therapies, immunotherapies, radiation, and hematopoietic cell transplantation [HCT]) continue to improve outcomes and extend the lives of our patients. However, nearly all patients will experience some side effects of these life-saving treatments. Treatment-related adverse events (AEs) affect patients’ overall health, including quality of life, and may lead to treatment delays or interruptions that can affect clinical outcomes.

Early identification is key to managing AEs. Establishing rapport and maintaining open communication with our patients is of the utmost importance for being clued in early to any potential side effects, allowing for easier management and lessening severity. As advanced practice providers (APPs), our clinical knowledge and experience, together with our close relationships with patients, put us on the frontline of identifying and managing AEs.

With the advent of newer targeted therapies and immunotherapies, we are seeing a whole new set of toxicities and adverse events.

Knowing What to Expect

I practice in both inpatient and outpatient settings, supporting all physicians in our HCT program. This means I see patients with a variety of underlying hematologic malignancies at varying stages in their treatment receiving a broad range of therapies – each with their own side effect profile.

To support clinicians in the management of AEs, our program developed comprehensive guidelines of chemotherapy regimens and their anticipated side effects. These guidelines are largely based on the AEs outlined in the package inserts (PIs) approved by the U.S. Food and Drug Administration, as well as in published clinical trials data. Management can involve holding the drug, reducing its dose, delaying treatment, or introducing new therapies to treat AEs. Specific parameters requiring dose reductions or delaying treatment are usually specified in the PIs.

Before a patient visit, my first step is to review his or her treatment plan and our guidelines to help identify potential issues that could arise during treatment. I also refer to drug databases to identify the AEs experienced during the clinical trials that led to the guideline’s recommendations.

Because I also manage patients who are enrolled in clinical trials at our institution, I carefully review the trial protocols to identify potential pitfalls and AEs we might encounter. Our clinical research coordinators, pharmacists, and primary investigators also are invaluable resources for identifying and managing AEs in our patient population. With the advent of newer targeted therapies and immunotherapies such as checkpoint inhibitors and chimeric antigen receptor T-cell therapies, we are seeing a whole new set of toxicities and AEs.

While clinicians are accustomed to handling the “traditional” side effects of cytotoxic therapies (e.g., infections, gastrointestinal toxicity, mucositis, and nausea), novel mechanisms of action mean different AE profiles and different management strategies. We are now seeing more “non-traditional” and immune-related AEs (such as cytokine release syndrome, neurotoxicity, endocrinopathies and other previously uncommon inflammatory sequelae) that require educating ourselves about the toxicity profiles of these new therapies and the medications to manage them.

Calling in the Troops

To manage our patients with hematologic malignancies, we rely on our whole team and expect everybody in the group to practice to the best of his or her ability.

Before seeing a patient, I touch base with our nursing staff. Our nurses do an excellent job of obtaining patient histories, reviewing symptoms, and identifying problems early during treatment. I rely on their input and make sure that we, as a team, are abreast of any clinical changes our patients may be experiencing.

Once we identify any AEs, we typically go through our standard management guidelines. If the AEs are atypical or not “clear-cut,” I confer with my APP colleagues and our clinical pharmacist or check in with the primary hematologist/ oncologist for advice on how to manage the AE.

In the outpatient setting, our APPs staff the clinic and infusion center and are heavily involved in caring for patients. We also have a proactive system for non-visit follow-ups; a triage nurse checks in with patients a day or two following the identification of an AE to monitor for any progression of symptoms or failure of our interventions. In addition, we provide our patients with educational materials and a phone number to reach us at 24/7 if any changes occur. We work closely with our inpatient team should the patient require hospitalization for further toxicity management.

Every APP has a different threshold for deciding what should be reported to the attending hematologist/oncologist immediately. For me, the urgency to notify the physician is guided by the severity of the toxicity or if I anticipate it will require management changes such as delaying or adjusting treatment.

In our practice, APPs typically handle acute symptom management. For example, if a patient experiences a common or mild AE (like gastrointestinal toxicity with nausea, vomiting, constipation, or diarrhea), the management is up to my clinical discretion. For rare AEs that aren’t thoroughly covered in previous literature or clinical trial experience, or for serious AEs that can affect the treatment plan, I discuss the situation with the hematologist/oncologist and develop a plan as to how to proceed.

Fortunately, our program fosters open communication and great working relationships across our entire team, and APPs are often not even faced with the question of whether to notify the primary hematologist/oncologist of an AE, regardless of severity. Our collaborative approach ultimately enables us to standardize the management of treatment-related AEs, overcoming the challenges that arise with both traditional and novel therapies to provide optimal care for our patients.

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