Advances in cancer treatment have brought a range of potential issues hospitalists are likely to see in admitted patients – many of which can escalate quickly into life-threatening emergencies if they’re not handled properly, an oncologist said in a presentation at HM20 Virtual, hosted by the Society of Hospital Medicine.
Checkpoint inhibitors and CAR T-cell therapy – revolutions in fighting cancer but potential instigators of serious side effects because of the way they set the immune system in motion – can have consequences throughout the body, said, an oncologist at the Cleveland Clinic.
Checkpoint inhibitors, which cause the body to essentially take its foot off the break of the immune system, in particular have diverse effects, Dr. Kruse said.
“Suffice it to say that any odd symptom in any organ system in a patient on immunotherapy, or with a history of immunotherapy, can be cause for concern,” she said. Most common are skin, gut, endocrine, lung, and musculoskeletal involvement. Cardiovascular, hematologic, renal, neurologic, and ophthalmological effects are less common, but when they happen, they’re often dramatic and need urgent management.
With these medications –which include anti–programmed death-1 agents pembrolizumab and nivolumab and anti–PD-ligand 1 agents atezolizumab and avelumab, among others – rash is often seen first, followed by diarrhea and colitis. Hypophysitis, which requires intervention, and liver toxicity, which usually tapers off on its own, often occur about 6-8 weeks into treatment. There are no rigid rules for the arrival of these symptoms, however, Dr. Kruse said.
“We must have a high index of suspicion. ... They really can occur at any point after a patient has had even one dose of an immunologic agent,” she said.
In more serious cases, steroids are typically the go-to treatment, she added, because they will quickly tamp down the immune activation brought on by the medications.
“When these drugs first came out, we were all very concerned about adding steroids,” she said. “In follow-up studies, it actually looks like we don’t attenuate the anticancer response very much by instituting steroids when clinically appropriate. And so you all should feel very comfortable adding steroids while waiting to talk to oncology.”
In these cases, the steroid taper is done very slowly, over weeks or even months.
With CAR T-cell therapy – in which patients receive T cells to target liquid tumors – cytokine release syndrome (CRS) can occur, often within 14 days after treatment. Dr. Kruse cautioned that it can present with symptoms similar to tumor lysis syndrome or sepsis.
“Patients are at a high risk of bacterial infection, so antibiotics are advised,” she said.
In these cases, fever is often a harbinger, often arriving at least a day before the rest of the symptoms of CRS.
Early treatment with the interleukin-6 inhibitor tocilizumab is recommended for these patients, she said. This agent has been shown to have a 69% response rate in severe CRS and has no known effect on the efficacy of the CAR T-cell treatment.
Dr. Kruse also touched on several other conditions that can rise to the level of emergencies in cancer treatment:
- In cases of neutropenic fever, patients should be treated as soon as possible with antibiotics, and some solid-tumor patients at lower risk can be treated as outpatients, she said. Those with hematologic cancer, however, will need inpatient care.
- For tumor lysis syndrome with renal failure, fluids should be started quickly. Rasburicase, a recombinant urate oxidase enzyme, can be considered in some cases, but requires caution.
- In cases of spinal cord compression, a full spine MRI should be completed because about a third of patients have multilevel involvement. Steroids should be started as soon as possible.
In a question-and-answer session, much of the discussion focused on when outpatient care for neutropenic fever was possible. Dr. Kruse said those who need to be admitted for neutropenic fever treatment tend to be those with hematologic malignancies because their treatment is so myelosuppressive.
“Their window of complications is longer,” she said. Solid tumor patients, on the other hand, will usually improve “fairly rapidly” in about 3-4 days.
Many session viewers expressed surprise at the possibility of outpatient neutropenic fever treatment. Dr. Kruse said that the Cleveland Clinic’s incorporation of this approach has included the input of neutropenic fever risk index scoring into their electronic medical record and a good deal of in-service training.
Asked about appropriate swabbing of patients for COVID-19 before chemotherapy, Dr. Kruse said that her center screens only patients who need to be hospitalized for the treatment – those with a high incidence of prolonged neutropenia.
“For our typical outpatients who are receiving chemotherapy,” she said, “we are not swabbing them.” But they have intense fever screening and distance measures in place.
Dr. Kruse reported advisory board involvement for Novartis Oncology and consulting for Puma Biotechnology.