Patients with advanced melanoma who received adjuvant therapy with pembrolizumab and subsequently developed immune-related adverse events (irAEs) saw a 63% reduced risk of recurrence, compared to 44% for those who did not develop irAEs. The study findings were presented at the 2019 American Society of Clinical Oncology annual meeting.

By rebalancing the immune system and re-engaging mechanisms that tumor cells have shut off, immunotherapies such as immune checkpoint inhibitors enable patients’ own bodies to fight their cancers for them. But those same mechanisms can also result in immune-related adverse events (irAEs).

Pembrolizumab, lenalidomide, and avelumab all received new treatment indications in spring 2019. Here’s what you need to know about dosing, adverse events, and other nursing considerations for these and other drugs that the U.S. Food and Drug Administration (FDA) approved from April–June 2019.

Pneumonitis is inflammation of the lung parenchyma; although rare, it can be fatal. Nishino et al. found that the overall incidence of pneumonitis with PD-1 inhibitor monotherapy was 2.7% for all-grade and 0.8% for grade 3 or higher pneumonitis. Naidoo et al. reported an approximate 5% incidence of all-grade pneumonitis, although the incidence of all-grade pneumonitis is higher with combination immunotherapy (up to 10%). The incidence is more common with higher grades in PD-1 inhibitors (versus PD-L1 inhibitors), but it occurs less often with anti-CTLA4 monoclonal antibodies. 

Researchers are testing a new approach using an amphiphilic cancer vaccine to deliver CAR T-cell therapy to solid tumors, and the results of preclinical studies are promising, according to findings published in the journal Science.

On September 17, 2019, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the combination of pembrolizumab (Keytruda^®) plus lenvatinib (Lenvima^®) for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation.

Two-year survival rates for patients with advanced melanoma increased quickly after the introduction of ipilimumab in 2011, according to an analysis published the journal Cancer.

The decision to allow Medicare to cover the cost of CAR T-cell therapy—a new and expensive form of immunotherapy—is an important one for patients seeking the treatment, especially after rounds of failed tradition therapies. Educating federal agencies and government representatives about the importance of new treatments like CAR T cells have helped drive coverage decisions, and the patient advocacy community—like ONS’s very own advocates—are to thank.

It’s an extraordinary time for biomedical research. Advancements in science, investments in research studies, and an increased access to patients through clinical trials have continued to transform the medical community’s understanding of cancer care and the best ways to treat and cure tumors. Achieving successful outcomes requires specific and dedicated therapies, tailored to each individual.

Two recent studies demonstrated CAR T-cell therapy activity in certain types of solid tumors, according to results presented at the American Society of Clinical Oncology annual meeting. The CAR T cells used new targets outside of the CD19 targets used for the therapy’s current approvals in leukemia and lymphoma. 
 

Care coordination, appropriate adverse event assessment and treatment, and rapid, continuous learning are essential priorities for oncology nurses to care for patients receiving immunotherapy, according to the experts who participated in ONS’s immunotherapy summit in March 2018. 

On July 30, 2019, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda®) for patients with recurrent, locally advanced or metastatic, squamous cell carcinoma of the esophagus (ESCC) whose tumors express PD-L1 (combined positive score [CPS] ≥10), as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Dermatologic toxicity is the most common side effect secondary to immunotherapy. The majority of dermatologic adverse events are mild to moderate rashes on the truck of the body and upper extremities, pruritis, and vitiligo. The most common is maculopapular rash with erythematous macules, papules, and/or plaques that can sometimes be scaly; pruritis is also frequent but often underreported and undertreated and may affect quality of life.

The U.S. Food and Drug Administration (FDA) first approved atezolizumab (Tecentriq^®) in 2016, but it received additional approvals when used in combination treatments for locally advanced or metastatic triple negative breast cancer (TNBC) and small cell lung cancer (SCLC) in March 2019.

Fresenius Kabi USA, LLC, is voluntarily recalling two lots of fluorouracil injection, USP 5 g/100 mL (50 mg/mL), 100 mL fill in 100 mL vials, to the user level because of the potential for glass particulate. The affected lots, distributed between December 6, 2018, and February 20, 2019, are listed below:

As of February 2019, only 160 institutions across the United States are certified to administer CAR T-cell therapy, meaning many eligible patients may need to be referred to a treatment center outside of the local ambulatory or community cancer center where they had previously received treatment. The transition from primary oncologist to certified center and back again requires careful coordination to ensure important steps and information aren’t lost.

On June 27, 2019, the U.S. Food and Drug Administration (FDA) approved daratumumab (Darzalex^®) in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.

Because two oral therapies received new indications in the U.S. Food and Drug Administration’s (FDA’s) most recent round of approvals, oncology nurses will want to focus on ways to manage patients in the home. Assessing oral adherence, encouraging patients to report adverse events, and ensuring their understanding of complex dosing regimens are critical components of nursing care. ONS offers an oral adherence toolkit and oral chemotherapy patient education sheets to help with patient management. 

On June 17, 2019, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab (Keytruda®) for patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy.

On June 10, 2019, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda®) for the first-line treatment of patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC).

As more patients receive treatment with chimeric antigen receptor (CAR) T-cell therapy, oncology nurses will need to be aware of the long-term effects of treatment that may persist into survivorship. However, because the treatment is so new, studies measuring those patient-reported concerns are still forthcoming. The majority of today’s recommendations for survivorship management are based on experts’ clinical experience.

On June 10, 2019, the U.S. Food and Drug Administration (FDA) granted accelerated approval to polatuzumab vedotin-piiq (Polivy^TM), a CD79b-directed antibody-drug conjugate indicated in combination with bendamustine and a rituximab product for adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, after at least two prior therapies.

Although immunotherapy has a unique set of toxicities compared to traditional chemotherapy, in general, grade 3 or 4 toxicities are rare—with the exception of grade 3 diarrhea and colitis. The mechanisms by which immune-related diarrhea and colitis occur are not clear. However, T-cell activation leads to high levels of CD4 T-helper cell cytokines and cytolytic CD8 T-cell tissue infiltration. Some research suggests that depleting regulatory T cells also induces autoimmunity.

Preliminary results reported in Nature Medicine showed that a redesigned CAR T-cell therapy produced complete response with no severe toxicities in 25 patients with refractory B-cell lymphoma.

Advanced practice RNs (APRNs), especially those with Doctorate of Nursing Practice degrees, in clinics across the country must not only focus on managing care for patients on novel therapies like immunotherapy but must also look at toxicities and adverse events from a population perspective. APRNs should look across all patients and disease types receiving the same novel treatments and recognize toxicity patterns to determine best practices for patient management. 

Clinical practice is in a constant state of evolution as new guidelines are released, drugs are approved for new indications, and technology reshapes the way care is delivered. Patients are also arming themselves with a more-advanced-than-ever knowledge and understanding of health care, and providers may be fielding new questions from patients and caregivers about novel treatments such as chimeric antigen receptor (CAR) T-cell therapy and biosimilars. 

A high-fiber diet leading to higher gut microbiome diversity may improve response to anti-PD-1 immunotherapy in patients with melanoma, according to the results of a new study presented at the 2019 American Association for Cancer Research Annual Meeting in Atlanta, GA. 

Immunotherapy may place patients at risk for distinctive toxicities that differ from traditional chemotherapy. One example is endocrine dysfunction, including hypophysitis, hypo- or hyperthyroidism, type 1 diabetes, and primary adrenal insufficiency. 

On April 19, 2019, the U.S. Food and Drug Administration (FDA) approved pembrolizumab plus axitinib for the first-line treatment of patients with advanced renal cell carcinoma.

A. Adoptive transfer 

B. Antibody-dependent cellular cytotoxicity 

C. Pathogen associated molecular patterns 

D. Phagocytosis 

On March 18, 2019, the U.S. Food and Drug Administration (FDA) approved atezolizumab in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer.

Using chemotherapy with immune checkpoint inhibitors may reactivate tumors’ responses to immunotherapy, researchers concluded in a review article published in the Annals of Oncology.

On March 8, 2019, the U.S. Food and Drug Administration (FDA) granted accelerated approval to atezolizumab in combination with paclitaxel protein-bound for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] of any intensity covering ≥ 1% of the tumor area), as determined by an FDA-approved test.

Pediatric cancers have more than an 80% overall cure rate, and that, at first glance, seems like something to celebrate. However, in terms of lives lost to different pediatric cancers, the American Cancer Society estimated that more than 1,100 children under the age of 15 will die from their disease in 2019—roughly one in five children diagnosed. Although survival rates are improving in cancers like acute lymphocytic leukemia and Hodgkin lymphoma, other childhood cancer types haven’t seen increased survival since the early 2000s.

To improve access to new cancer therapies and provide national consistency in coverage, on February 15, 2019, the Centers for Medicare and Medicaid Services (CMS) announced a proposed plan of coverage with evidence development for CAR T-cell therapy. The public is invited to share comments for the next 30 days.

Immunotherapy has a unique set of toxicities in comparison to traditional chemotherapy. Endocrine dysfunction, including hypo- or hyperthyroidism, hypophysitis, type-1 diabetes, and primary adrenal insufficiency, may occur. Advanced practice RNs (APRNs) have a role in monitoring and treating patients for endocrine-related toxicities.

On February 15, 2019, the U.S. Food and Drug Administration (FDA) approved pembrolizumab for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection. 

Although the National Cancer Institute on the National Institutes of Health (NIH) campus bears the bulk of research dollars for new discoveries and treatments, other campus institutes engage in cancer research and support. Researchers from the National Heart, Lung, and Blood Institute (NHLBI) are conducting a new study investigating novel immunotherapy treatments for metastatic kidney cancer.

When evaluated based on the cost per life-year gained, the chimeric antigen receptor (CAR) T-cell immunotherapy drug tisgenlecleucel is considered cost effective in pediatric B-cell acute lymphoblastic leukemia, researchers reported in a new study. The findings were published in JAMA Pediatrics.

Still a popular program throughout the government, the Cancer Moonshot Initiative challenged the United States to meet goals to accelerate cancer research progress, encourage collaboration in finding treatments and cures, and to improve data sharing to make a decade’s progress in half the time. Through NIH’s Moonshot Blue Ribbon Panel and the 2016 passage of the 21st Century Cures Act—allocating $1.8 billion over seven years for Moonshot—the initiative is moving out of planning and into the research phase.

Some patients receiving checkpoint inhibitors for lung cancer may experience increased risk for hyperprogressive disease (HPD), according to results of a study reported in JAMA Oncology.

One way that cancer has been able to evade the immune system is through overexpression of immune checkpoint proteins (immune inhibitory pathway), which allow cancer cells to be considered “self” instead of foreign and block T-cell action. Immune checkpoint proteins cytotoxic T-lymphocyte–associated 4 (CTLA-4) and programmed cell death protein (PD-1) are receptors that are expressed on the surface of cytotoxic T cells. Immune checkpoint inhibitors prevent those receptors from binding to their natural ligands, disrupting the immune inhibitory pathway. See Table 1 for a list of approved agents and indications.  

Two researchers whose discoveries led to the development of the first cancer immunotherapy treatments, immune checkpoint inhibitors, were awarded the 2018 Nobel Prize in Medicine in October.

On November 16, 2018, the U.S. Food and Drug Administration (FDA) approved brentuximab vedotin in combination with chemotherapy for previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified. This is the first FDA approval for previously untreated PTCL including sALCL.

On November 9, 2018, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab (Keytruda) for patients with hepatocellular carcinoma who have been previously treated with sorafenib.