The number of FDA approved CAR T-cell therapies has increased from 3 to 5 drugs in the past year. This novel treatment regime shows promise to continue to evolve in the coming years, providing hope for patients with relapsed hematologic malignancies that failed to respond to prior chemotherapy treatments, says Kelly Garvin, BSN, RN, OCN.

In a recent interview with Oncology Nursing News®, Garvin, from the Department of Malignant Hematology, H. Lee Moffit Cancer Center, discussed her 

School of Nursing Oncology meeting. She outlined how nurses can 

 in detecting CAR T-related adverse events (AEs), and commented on how the evolution of CAR T-cell therapy has continued to change the prognosis for patients with blood cancer and where she hopes the treatment direction will go.

Oncology Nursing News: How can nurses anticipate, and respond aggressively to, CAR T-cell therapy-related AEs?

Good question. One thing that we do is we have specially trained nursing staff. So, the nurses that work on the CAR T-cell floor are almost intensivists. In other words, we can float nurses from the intensive care unit to the CAR T-cell floor, but we cannot load nurses from MedSurg to the CAR T[-cell therapy] floor. So, these nurses, first of all, have to be specially trained in how to recognize the signs and symptoms of cytokine release syndrome, neurotoxicity, and ICANS.

Another thing that we do is we take vital signs more often. So, instead of [taking vitals] once a shift, we do it every 4 hours. We can do a cranial nerve check every time we go in there. We can be on the lookout for signs like headaches, aphasia, or confusion. We can ask the patient to write out a sentence and notice if there's any tremors in their penmanship that might be indicative that something is brewing. We can take their temperature more often. We can use family members to help us and alert us if the patient seems a little off. So, things like that all work together to keep the patient safe.

Would you be able to comment on how CAR T-cell therapy has changed the outcomes and prognosis of patients with blood cancers?

Oh, this is my favorite thing to talk about. So much has happened recently. Last year, I gave this talk, and, at the time, there were only 3 products that were FDA approved for certain malignancies, and 1 of them had been approved days before I gave the talk. In fact, I had to redo all the slides just to include them. Now, there are 5 different products and there are more indications.

So, if I have a patient who, for example, [has] diffuse large B-cell lymphoma, 1 of the most common non-Hodgkin lymphomas diagnosed in the United States every year, and is very aggressive, [the] good news is that we can cure about two-thirds of these patients with traditional archtop chemotherapy and immunotherapy. But for the one-third who relapse, or don't respond, the data is not good. There's not much we can do. Standard of care says [to] try salvage chemotherapy and then take them to autologous stem cell transplant. But if chemotherapy didn't work that well the first time what's to say heavy duty chemotherapy is going to work the second time. Right now, there's a trial going on in my cancer center looking at whether CAR T-cell therapy is just as good or maybe even better than standard of care. So, for patients who maybe have poor prognosticating factors, like bad genetics, or maybe they have BCL2 or BCL6 translocation or overexpression, and it doesn't look like they're probably going to respond very well to chemotherapy, if we could take those patients, and identify them early and take them to CAR T-cell therapy, where we're not using chemotherapy to fight the disease, we're using the body and the patient's own immune system, might they have a better outcome? Might their remission be deeper and longer? That's what we're going for.

And what do you hope to see in the next 5 to 10 years?

So many good things. So, one of the hurdles that we have to get over with CAR T-cell therapy is that we're using the patient's own T cells, and we're sending them off to be manufactured and to be reprogrammed in a way that is better able to fight the cancer. But sometimes that process takes too long. These are patients who have seen multiple lines of therapy. By the time they get to CAR T-cell therapy, they might not be able to wait the 2, 4, or, in some cases, even 6 weeks to get those T cells manufactured for them. So, 1 thing that we're looking at is allogeneic T-cell therapy or off-the-shelf [therapy]. So, we'll have donor T cells, kind of like we have donor allogeneic stem cell transplant. So that's 1 area.

Another area is more indications. Can we use CAR T-cell therapy for other diseases? For example, follicular lymphoma, which often transforms into diffuse large B-cell [lymphoma], can we use it in follicular lymphoma, just like we can in diffuse large B-cell [lymphoma] to get better outcomes for these patients? As a matter of fact? Yes. Axicabtagene ciloleucel (Yescarta), the first generation CAR T-cell therapy, just became approved in that particular setting as well.

Another thing I'd like to see is maybe using CAR T-cell therapy as first[-line therapy] rather than in the relapsed/refractory setting. So, would it be better to maybe replace chemotherapy sometimes or replace stem cell transplant in some cases, and start with CAR T-cell therapy for some of these patients, especially if they have 

mutations, or other genetic markers that lead us to suspect maybe they're not going to respond very well to chemo? Let's start thinking: Can we use immunotherapy instead? That's what I'd like to see.

What is the grand takeaway for oncology nurses from your presentation?

Well, on a very tangible level, nurses who already do oncology and who see patients that have these B-cell malignancies, these multiple myelomas and these diffuse large B-cell [and[ follicular or mantle cell [lymphomas], they’re going to know how to prepare the patients that they've identified as good candidates for what CAR T-cell therapy will feel like and look like for the patient. So that's 1 thing.

And for the other nurses who maybe don't do lymphomas, I want to leave them with this idea: CAR T-cell therapy is huge. It's exciting. It's dynamic. And it's a very fun place to be in medicine right now. And stay tuned, more is coming down the pipeline.

Articles

Kelly Garvin, BSN, RN, OCN, discusses the impact of CAR T-cell therapy on patients and how nurses care for them, as well as her expectations on how indications will grow. 

CAR T-Cell Therapy Continues to Revolutionize Hematologic Cancer Treatment

Kelly L. Garvin, BSN, RN, OCN, H. Lee Moffit Cancer Center, discusses where she hopes to see the direction of 

chimeric antigen receptor (CAR) T-cell therapy

 go over the next 5 to 10 years, in an interview with Oncology Nursing News®. Garvin recently presented about 

managing CAR T-cell therapy-related adverse events (AEs)

Some of the CAR T-therapy applications that Garvin would like to see include expanded approvals to use the therapy to treat other diseases and other lymphomas, as well as to potentially have the therapy approved as an earlier treatment for patients with TP53 or other biomarkers that suggest they won’t respond well to chemotherapy. One other change Garvin hopes to see is a shortened wait time to get the manufactured T cells ready for the patients.

“Sometimes [the] process takes too long,” she said. “These are patients who have seen multiple lines of therapy. By the time they get to CAR T[-cell therapy], they may not be able to wait the 2, 4, or even 6 weeks it takes to get those T cells manufactured for them. So, one thing we’re looking at is allogeneic T-cell therapy, or off-the-shelf... so we’ll have doner T cells, kind of like how we have donor allogeneic stem cell transplants.”

Overall, Garvin wants nurses to take away the idea that “CAR T[-cell therapy] is huge, it’s exciting, its dynamic, and it’s a very fun place to be in medicine right now and [nurses should] stay tuned­. More is coming down the pipeline.”

Videos

Kelly L. Garvin, BSN, RN, OCN, discusses what changes she hopes to see in CAR T-Cell therapy treatment over the coming years. 

Expert Weighs in on Future of CAR T-Cell Therapy Treatment Directions

Patients with non-small cell lung cancer (NSCLC) and specific driver mutations respond better to targeted therapy compared with chemotherapy, explained Beth Sandy, MSN, CRNP, Abramson Cancer Center, University of Pennsylvania, during a presentation at the 5th Annual School of Nursing Oncology Meeting.

According to a pooled analysis of patients who received National Comprehensive Cancer Network (NCCN)-guided therapies in accordance with their biomarkers, overall survival (OS) was significantly improved in patients who receive targeted therapy (18.6 months) compared with patients who do not received targeted therapy (11.4 months).

“You can never treat a mutation that you never found,” emphasized Sandy. “We must test and find out what this biomarker is because [their treatment] is going to be better if they get their targeted therapy for that driver mutation.”

Current NCCN recommendations for biomarker testing say that, whenever feasible, providers should recommend a broad panel-based, molecular test. Next generation sequencing (NGS) is the most common way to complete this. These can be performed either in-house or through a commercial company. If no biomarkers are uncovered, providers should consider an RNA sequencing panel to detect RNA fusions.

In addition, all patients with metastatic NSCLC with non-squamous histologic subtypes should be tested for biomarkers. Testing should be considered in any patients with squamous histology or with early stage resected NSCLC. The minimum testing recommendations include 

; however, testing should be considered for 

Yet, despite the NCCN guidelines, less than 50% of patients with NSCLC are actually tested for the minimum 5 recommended biomarkers, according to the MYLUNG Consortium Data, presented at the 2021 ASCO annual meeting.

NGS is a broad molecular panel that tests for over 100 gene alterations. While there only 9 necessary tests, each additional test can help guide treatment. Additionally, even the variant of uncertain significance can be useful for future clinical trials, Sandy said.

NGS tests are often more efficient than individual tests for different biomarkers because it requires less tissue. While they may have a reputation for being expensive for the patient, Sandy says that most companies will absorb or reduce the payment.

She also outlined reflex testing, or the testing of all samples of NSCLC that has been identified by pathologists as non-squamous histology. The diagnostician who performs the biopsy suspected to be NSCLC will automatically check a box ordering the molecular test.

It is important to note that the pathologist cannot order the test because it is considered a conflict of interest. This new way of ordering tests is much quicker because now the medical oncologist has the results, or they are being processed by the time they see the patient.

Current challenges for molecular testing include the fact that lung cancer biopsies are less cellular than other solid tumors. Bone biopsies yield poor samples; they need to be decalcified. Furthermore, the tests can take weeks so they can present a logistical challenge. Occasionally, the test can return saying QNS, or quality not sufficient, which means that all the efforts need to be attempted again from square 1. There needs to be 10% to 20% of viable cancer cells in the sample to get a reliable result.

DNA sequencing scans tissue for an activating somatic mutation, like insertions, point substitutions, and in-frame deletions. This test will detect mutations in 

. DNA sequencing can be performed via PCR, a direct sequencing or NGS. Direct sequencing tends to be the most tedious and time consuming.

RNA fusion panels differ from DNA sequencing because they detect gene rearrangements, not mutations. 

 are all fusion abnormalities that are through these tests. While these aren’t necessarily clinically useful in NSCLC, they can be helpful for future clinical trials. 

 can both be detected through fluorescence in situ hybridization (FISH) or HCL, although the latter is not considered an acceptable result per NCCN guidelines.

Sandy acknowledged that the results of these tests can be difficult to decipher, “One time my RNA fusion reported an 

 mutation. And I was like, ‘Oh, they have 

,’ I called molecular pathology, and they said, ‘No, no, no, that's a gene rearrangement, not a DNA mutation… So, don't be afraid to call molecular pathology, I have them on speed dial.”

Liquid biopsies can work great in conjunction with a tissue biopsy, said Sandy. The advantages of the blood test are its minimally invasive nature, and its strong ability to detect any resistance mutations. Unfortunately, the liquid biopsy functions by detecting DNA shedding from the tumor in the bloodstream, and shedding can vary. So, depending on the day, the test’s sensitivity might be different. In addition, these tests cannot detect histology, and cannot therefore determine a “small cell transformation” from 

The Nile study (NCT03615443) found that performing both tissue and liquid biopsy identifies the highest amount of circulating tumor DNA (ctDNA) and the highest number of mutations. Some institutions, including the Abramson Cancer Center hospital at the University of Pennsylvania in Philadelphia, where Sandy works, perform both the blood and tissue scans on their patients. “Test. Test. Test.” she emphasized.

Approved Targeted Therapies for Different Driver Mutations

Sandy also outlined different approved agents that are preferred to treat common mutations in NSCLC.

Osimertinib (Tagrisso) is the preferred treatment for 

 exon 19 or 21. These mutations are fairly common: They consist of about 30% of 

 mutations. Osimertinib demonstrated superiority over erlotinib (Tarceva) and dacomitinib (Visimpro) in the FLAURA trial (NCT02296125) through a clinically significant improvement in progression-free survival (PFS). Patients in the osimertinib arm reported a PFS of 18.9 months, compared with 10.2 months with either erlotinib or dacomitinib. With a hazard ratio (HR) of (95% CI, 0.37-0.57; 

 < .0001), it was pretty clear evidence, Sandy said.

While some patients reported grade 1 or 2 rash in clinical trial, these symptoms can usually be managed with topicals or doxycycline. About half of trial patients also reported diarrhea, and that is manageable with over-the-counter anti-diarrheal agents. Overall, the drug is fairly tolerable.

Osimertinib is also now approved in the early stage, post-operative setting.

 mutations, however, it is actionable, and it has approved targeted therapy, amavantamab (Rybrevant). Sandy noted that “this is the only target therapy that's IV. It's a monoclonal antibody, and it's got a pretty odd administration, scheduled weekly for 4 weeks and every other week as a high infusion reaction with the first dose… but it's not analyphylactic, it's usually mild, and we can get them through it.”

ALK inhibitors make up about 4% to 6% of NSCLC and their preferred first-line treatment include alectinib (Alecensa), brigatinib (Alunbrig), lorlatinib (Lorbrena), and alectinib is also recommended for second- andthird-line treatment.

, though uncommon, makes up to 3% of NSCLC cases, and has 4 approved drugs that are recommended in accordance with NCCN guidelines: crizotinib (Xalkori), entrectinib (Rozlytrek), ceritinib (Zykadia), and lorlatinib. Crizotinib is the most trusted treatment of those 4.

Sotorasib (Lumakras) is the recommended drug for a 

mutation. Sandy advised that nurses should “remember that this is more common in smokers. So again, we’ve got to be testing everybody, not just the never-smokers. It's a pill and it's taken in 8 tabs daily, all at once. So, this is a little bit hard for adherence. We have to work with these patients for sure.”

Dabrafenib (Tafinlar) plus trametinib (Mekinist) is recommended for 

, which is more common in smokers than non-smokers. MET exon14 skipping has 3 approved agents: capmatinib (Tabrecta), crizotinib, and tepotinib (Tepmetko), while a RET rearrangement can be treated by the any of the following 4: selpercatinib (Retevmo), pralsetinib (Gavreto), cabozantinib (Cabometyx), and vandetanib (Caprelsa). 

, though extremely rare (less than 1 out of 1,000 cases), has 2 approved targeted drugs: entrectinib and larotrectinib (Vitrakvi).

“Our take home messages here are that the NCCN guidelines recommend testing in these populations of patients, especially the non-squamous [NSCLC], which is [the] majority, and adenocarcinoma. You can never treat a mutation that you never found,” said Sandy.

With so many approved targetable agents available in the metastatic setting, (as well as 1 approved drug in the early-stage setting), each with different dosages, and adverse event profiles, there is a lot more for nurses to keep up with, Sandy concluded. Her best advice? A team-based approach. Diagnosticians, medical oncologists, oncology nurses, and pathology all need to collaborate and communicate in order to ensure that patients are being tested and that the patient has access to the best resources available to treat their disease.

Sandy B. Molecular Testing and Targeted Therapies in NSCLC. Presented at: 5th Annual School of Nursing Oncology; August 6-7, 2021; Virtual.

Patients with non-small cell lung cancer driver mutations respond better to targeted treatments compared to chemotherapy, yet less than half of these patients receive next generation sequencing. 

More Broad Molecular Tests Are Needed to Accurately Treat Non-Small Cell Lung Cancer

Oncology nurses taking care of patients treated with immunotherapy can ensure they continue to receive this therapy and lower hospitalizations by remaining diligent in suspecting and detecting immune-related adverse events (irAEs), said Grace Cherry, RN, MS, NP, UCLA melanoma program, during a presentation at the 5th Annual School of Nursing Oncology meeting.

“If you're an oncology nurse, you will have patients with immunotherapy–which is why we want to make sure that we are really familiar with these side effects,” Cherry emphasized.

IrAEs are currently unpredictable. They can appear at any time, in any organ or tissue. There are currently no markers to indicate which patients will have a reaction, although it is suspected that those who are autoimmune are at greater risk.

Common irAEs include fatigue, dermatitis, colitis, endocrinopathies, hepatitis, and pneumonitis. However, there are also rare irAEs that can occur, such as neurological, hematological, cardiac, musculoskeletal, and renal symptoms. Cherry urges oncology nurses to always “be suspicious.”

“I would like to invite for you to be that person who will be suspicious. Be that person who will [ask]: Is this an immune related adverse event?” encouraged Cherry. “And report it… because if it is [an irAE] we can treat them with prednisone, and the expectation is that it will get better.”

The primary principle of irAE management is early diagnosis. For this to be possible, patients must be taught to communicate any change they experience.

Communication, communication, communication,” stressed Cherry. “We have to let them know how to communicate to us if they're having symptoms. Do they know who to call? Do they have a phone number? Do they know to call on the weekend if they’re having a cough or profuse diarrhea?

The second step is to rule out other causes. IrAEs are unpredictable and difficult to diagnose, so Cherry advises involving other specialists with different instruments and training whenever possible. For example, if a patient experiences blurry vision, it is important to call an ophthalmologist, because they can look inside the eyeballs and provide a truly thorough evaluation.Using an interdisciplinary team is often the best way to receive early and accurate diagnoses.

Cherry also emphasized the importance of understanding common terminology criteria for adverse event (CTCAE) because it provides clinicians with a common language. Generally, immunotherapy can be continued with frequent monitoring as long as the AE is grade 1.

Grade 2 indicates that immunotherapy should be held, and symptoms managed. If symptoms are improved to grade 1, the therapy can continue. Glucocorticosteroids are recommended at 0.5–mg/kg per day if symptoms persist beyond 5 to 7 days.

If symptoms are not improved with use of steroids and worsen to a grade 3, not only should immunotherapy be held, but the glucocorticosteroids dosage should be increased to 1 to 2 mg/kg per day and hospitalization should be considered.

If the irAE reaches grade 4, therapy should be discontinued, and the patient should receive urgent intervention.

There are currently 7 FDA approved immunotherapies. Anti-PD-1 therapies such as nivolumab (Opdivo), pembrolizumab (Keytruda), and cemiplimab (Libtayo), are generally much better tolerated than anti-PD-L1 drugs like atezolizumab (Tecentriq), avelumab (Bavencio), and durvalumab (Imfinzi), or the anti-ctla-4 therapy, ipilimumab (Yervoy).

The standard treatment for irAE is systemic steroids therapy; 0.5 to 2 mg/kg/d of prednisone or equivalent should be administered in either IV or oral form, depending on the severity, and should be tapered gradually over the next 4 to 6 weeks. Various literature suggests that the use of steroids does not impact the efficacy of the immunotherapy, said Cherry.

If steroid therapy does not induce a positive response within 2 to 3 days, the next step is usually an immunosuppressant. Guidelines recommend infliximab for colitis, mycophenolate for hepatitis, and an antifungal prophylaxis for pneumocystis.

Prednisone can affect glucose levels, so blood sugar should be monitored when administering that steroid. In addition, PP1 and H2 blockers are recommended to prevent gastritis, while vitamin-d and calcium are encouraged to prevent osteoporosis.

Cherry reminded nurses that irAEs are treatable. She recounted how gratifying it feels as an oncology nurse to successfully catch and manage an irAE and allow a patient to continue treatment.

As an example, she recalled a patient who was successfully treated for their adrenal insufficiency with 20mg hydrocortisone twice a day and was consequently able to continue their monthly monotherapy of nivolumab.

“I have to say personally, it's really gratifying when we catch patients with adrenal insufficiency, because.. they look so sick, and they feel horrible, but when we properly diagnose, and give the supplement of hydrocortisone, symptoms immediately get better. So, it's really, really gratifying. But even more gratifying than that is they continue to take therapy that is lifesaving.”

Some patients receiving immunotherapy are apprehensive to receive the COVID-19 vaccine. However, the NCCN has stated that patients with cancer respond well to messenger RNA SARS-CoV-2 vaccines and should continue to be prioritized for immunizations. Exceptions include patients who have received stem call transplant, cellular therapy, major surgery or have acute leukemia.

Both the NCCN and the Society of Immunotherapy of Cancer have patient geared resources for understanding immunotherapy. Furthermore, both the NCCN and ASCO release regularly updated immunotherapy management guidelines for clinicians.

Cherry also urges that patients use immunotherapy wallet cards and that families and caregivers be incorporated in the symptom management process. Any change from baseline should be reported right away.

“Communication is the key. Communication with patients. Communication with other health care providers. Early reporting is so important, make sure your patients know who to call, how to call, how to report symptoms. Let them know what their baseline is. If it's anything different, report it to us. Our job is to figure out is this immune related or not… So, we continue to give these treatments safely, so that our patients can continue with their life saving treatments.”

Cherry G. Management of Immune Related Adverse Events (irAE). Presented at: 5th Annual School of Nursing Oncology; August 6-7, 2021; Virtual.

“If you're an oncology nurse, you will have patients with immunotherapy–which is why we want to make sure that we are really familiar with these side effects.”

Immunotherapy Related AEs Are Manageable with Nurse Intervention

Oncology nurses need adequate training to be able to recognize the signs and symptoms of CAR T-cell therapy-related adverse events (AEs) to ensure their patients can remain on their treatment, according to Kelly L. Garvin, BSN, RN, OCN.

Garvin, of the H. Lee Moffitt Cancer Center, recently spoke with Oncology Nursing News® and offered insight into how nurses could proactively help their patients manage CAR T-cell therapy-related AEs. Garvin recently presented on the topic at the 5th Annual School of Nursing Oncology.

Nurses who support patients receiving CAR T-cell treatments, Garvin noted, are specially trained to operate similarly to intensivists, which means they can float between the intensive care floor and the CAR T floor, while nurses from Med-Surg cannot. In addition, nurses who work with patients receiving CAR T treatments need to be able to recognize the early signs of cytokine release syndrome (CRS), neurotoxicity, and ICANS, before the symptoms begin to progress.

Garvin also noted that nurses should take their patients’ vital signs more often and perform other tasks to be quickly alerted if a patient is experiencing CAR T-cell therapy-related AEs.

“So, instead of once-a-shift, we (take vital signs) every four hours and do a cranial nerve check every time we go in there. We can look for signs like headaches, aphasia, or confusion,” she said. “We can (also) ask the patient to write out a sentence and see if there are any tremors in their penmanship.”

Garvin KL. CAR-T Therapy Nursing Considerations; Patient Education & Toxicity Management. Presented at: 5th Annual School of Nursing Oncology Live, Interactive Webcast. August 6-August 7, 20201.

Proper training can help oncology nurses act as intensivists and quickly identify if their patients are experiencing any CAR T-cell therapy-related adverse events. 



Oncology Nurses Who Proactively Manage CAR T-Cell Therapy-Related AEs Can Ensure Their Patients Remain on Treatment

Oncology nurses must understand how biosimilar products function and how they compare to other drugs on the market, according to a presenter at the 

Although the first biosimilar for the treatment of multiple cancers was not approved until 2017, oncology nurses have had to brush up on their knowledge of those drugs ever since Congress passed the Biologics Price Competition and Innovation Act in 2009.

Teresa Knoop, MSN, RN, AOCN, director at large, Oncology Nursing Society Board of Directors, outlined how nurses can differentiate between biosimilars and generic drugs.

The first thing that nurses need to understand, according to Knoop, is what a biosimilar is. A biosimilar is a biological product that has been approved by the FDA based on evidence that the drug is highly similar to a preexisting biological product (the reference product, or originator) that has also been FDA approved. For a biosimilar to be approved, it must demonstrate that it induces no clinically meaningful differences from the original product in terms of safety, purity, or potency. For the biosimilar to be accepted as highly similar, only minor differences in clinically inactive components are permissible.

As an example, Knoop explained that “the drug trastuzumab, which has been around since 1998, would be considered a reference or originator product. The biosimilars that are then produced have to have studies that prove the safety and efficacy against the originator the reference product, trastuzumab.”

Biologic products are often more difficult to characterize than small molecule drugs due to their generally large, complex nature, she said. They are produced in living systems using biotechnology.

While biosimilars go through abbreviated approval pathways, they are tested against reference products which were approved after undergoing a rigorous testing process and multiple phase 3 and phase 4 trials. The biosimilars are screened for their similarities to these approved original products through studies assessing pharmacokinetic exposure, pharmacodynamic response, clinical immunogenetic, and they are also screened through additional clinical studies, if needed.

Additionally, the immunogenetic assessments can also be quite rigorous as, according to Knoop, “they have to prove that this biosimilar is not creating an immunogenicity (which) means that your body is developing antibodies to the drugs. So, you have to prove that your body — with these biosimilars — (is) not producing anti-drug antibodies”

Difference Between Generic and Biosimilar Drugs

As Knoop explained, it is also important for oncology nurses to recognize how biosimilars differ from generic drugs. The two share certain similarities; they undergo abbreviated approval processes, they are both versions of brand name drugs, and they share the same active ingredients as the brand name drugs. Both drugs are also useful because they “help to complete the cost of clinical trials and shorten the time that we can get these drugs to market.”

However, the responsibility of biosimilar manufacturers differs from those who manufacture generic drugs because they need to prove that their product is highly like the originator or reference product and that there are no clinically meaningful differences between their product and the reference.

In addition, biosimilars are biologic products, while generic drugs consist of a chemical composition, and, because of this, the active ingredients in generics are the same as in the brand name. This is different than in biosimilars.

Knoop noted that, “it is acceptable that there will be a few product variations due to manufacturing because these are based on living mechanisms and biotechnology, even in a reference product. This is true in the reference product and the biosimilar is therefore also allowed to have those kinds of variations so long as they have no meaning on the outcome of the drug treatment.”

In continuation, a biosimilar might receive the same number of indications that its reference drug has, or it might have fewer. If an originator product has an unexpired exclusivity, this can impede on the corresponding biosimilar’s ability to obtain the same extent of indications. Knoop’s response was to encourage nurses to understand this and ensure that they review the prescribing information each time a new biosimilar is approved, so that they understand which indications the approval encompasses.

She also explained that an interchangeable product would be a biosimilar that has demonstrated such a high similarity to the original product that the two could be interchanged without consulting the prescriber.

As of now, no cancer biosimilars are interchangeable, partly because the amount of information needed for the FDA to approve an interchangeable product is extensive. The process involves multiple clinical trials, including “switching studies,” where the interchangeable product is switched with the original to certify that it produces the same clinical results in every patient.

Despite the number of years and clinical trials needed to approve an interchangeable biosimilar product for cancer, oncology nurses should watch for this and understand that manufacturers would need to prove that their product produces the same clinical result as the reference product for the FDA to conclude that the two are interchangeable.

Knoop offered a couple useful reminders on how oncology nurses can navigate the naming conventions of a couple different biosimilars. She explained that understanding the naming system and their connection to the mechanism of action and the target of the drug is an important aspect of anticipating adverse events.

To recap, “TU” indicates that a drug will target a tumor. Tras(tu)zumab is a great example, she said, because it targets HER2 breast cancer tumors and adverse events will therefore be related to targeting the tumor. A drug with “CI” refers to the circulatory system. Knoop explained that “in circulatory beva(ci)zumab, the target are the epithelial cells that grow in the circulatory system and are part of the tumor’s blood supply. This should alert nurses to look for circulatory adverse events, such as wound healing, bleeding, proteinuria, and circulatory high hypertension.”

Finally, an “L” or “Li” indicates that the drug is targeting the immune system. A great example of this, according to Knoop, is ipi(li)mumab. This monoclonal antibody functions by affecting the immune system. Understanding this allows nurses to proactively anticipate the patient’s responses.

Additionally, Knoop reminded nurses that in 2017, it was decided that all biologic products would have a suffix with four lowercase letters devoid of meaning attached to the name. Knoop stressed that nurses should recognize that not every new biologic product is a biosimilar.

“The FDA did not want biosimilars identified per se to it because they did not want to squelch competition, they wanted to make sure they were never seen as an inferior product,” she said. The FDA, according to Knoop, has therefore helped to foster a highly competitive, high quality market, which seeks to advance patient safety by allowing biosimilars a place to grow.

Knoop T. Biosimilars: Essentials for Oncology Nurses. Presented at: 5th Annual School of Nursing Oncology Live, Interactive Webcast. August 6-August 7, 20201.

Teresa Knoop, MSN, RN, AOCN, says it is important for oncology nurses to understand the naming convention of biosimilars as it is an important aspect of anticipating adverse events. 



Understanding the Essentials of Biosimilars: What Oncology Nurses Need to Know

Non-small cell lung cancer (NSCLC) can oftentimes be diagnosed at a later stage because there are few signs indicative of cancer when the disease first appears. However, by the time NSCLC becomes locally advanced — meaning it spread to the mediastinal nodes in the center of the chest – patients may start to experience symptoms, leading to their diagnosis, according to Beth Sandy, CRNP.

Standard of care still leaves much to be desired in the second-line setting for these patients. However, immunotherapy may be changing that.

Sandy, a nurse practitioner at the University of Pennsylvania Abramson Cancer Center, recently discussed treatment for locally advanced NSCLC at the 

 School of Nursing Oncology Live, Interactive Webcast.

“Once those lymph nodes get big … you start to have symptoms like shortness of breath,” Sandy said.

Experts are currently debating whether or not it is appropriate to conduct surgery on stage III locally advanced NSCLC, according to Sandy, who noted that the potential survival advantage of surgery could come with more adverse events.

“So it appears the concurrent chemo radiation is the better way to go,” Sandy said. “The median progression-free survival (PFS) is only about 8 to 10 months, meaning that patients often are going to recur in that first year after chemo radiation, if they’re going to recur.”

Sandy outlined 3 common drug regimens given with radiation:

Paclitaxel/carboplatin, given at a low dose once a week

Pemetrexed/carboplatin or cisplatin, given at a full dose every 3 weeks

Etoposide/cisplatin, with etoposide given on days 1 through 5 and cisplatin given on day 1 and day 8, repeating for 28 days

“Paclitaxel and carboplatin is probably the most common, as it’s the easiest to tolerate,” she said. “With pemetrexed and platinum cisplatin or carboplatin, the good thing about that regimen is that it’s full-dose… but it can be more toxic with full-dose chemo. Then, etoposide and cisplatin is kind of a middle-of-the road dose.”

After chemoradiation, there traditionally was no further treatment for patients with locally advanced NSCLC. However, the immunotherapy agent durvalumab (Imfinzi) has been showing benefit.

Findings from a randomized, phase 3 clinical trial (NCT02125461) showed that durvalumab (Imfinzi) improved outcomes in patients with stage III, locally advanced, unresectable NSCLC who have not progressed after 2 or more platinum-based chemotherapy/radiation treatments.

Durvalumab bested placebo in median PFS (16.8 months versus 5.6 months, respectively), as well as 12- (55.9% versus 35.3%) and 18-month PFS (44.2% versus 27.0%).

“With PFS, we had significant improvement [with durvalumab],” Sandy said. “

The immunotherapy agent was better than placebo in overall survival, too. In fact, at the 36-month mark, 57.0% of participants on the durvalumab arm were alive, compared to 43.5% on the placebo arm.

“You can see that there is a significant number of more patients alive at the 3-year mark. This is really exciting,” Sandy said. “Once we get to that 5-year overall survival, we can then look and see not only an overall survival, but also maybe that they’re never relapsing…our cure rates may be improving.”

Sandy B. Lung Cancer: Essentials for Oncology Nurses. Presented at: 

 School of Nursing Oncology Live, Interactive Webcast. July 31-August 1, 2020.

Dennis P. A Global Study to Assess the Effects of MEDI4736 Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (PACIFIC). Updated March 19, 2020.

Locally advanced non-small cell lung cancer traditionally had high relapse rates after initial treatment. Now durvalumab may bring better survival rates to these patients.

Durvalumab Boosts Survival Outcomes in Locally Advanced NSCLC

The advent of CAR T-cell therapy is a “game changer for blood cancers,” according to Kelly Garvin, MA, BSN, RN. However, they do have potentially lethal adverse events (AEs), highlighting the importance of specific training and education for nurses who are administering this treatment.

“CAR T-cell therapy is powerful with impressive success rates, but also with specific dangerous [adverse events] that require trained nursing staff to manage,” Garvin, a nurse at the Moffitt Cancer Center, said in a presentation at the 4

 Annual School of Nursing Oncology Live, Interactive webcast.

There are currently 4 FDA-approved CAR T-cell therapies, all indicated for patients with relapsed or refractory blood cancers: axicabtagene ciloleucel (Yescarta), brexucabtagene autoleucel (Tecartus), tisagenlecleucel (Kymriah), and tocilizumab (Actemra).

The treatments work by extracting blood from a patient and programming their T cells to recognize and attack cancer cells. That process can take 10 to 14 days, according to Garvin.

“While B cells develop a very specialized affinity for specific antigens, T cells are more like professional mercenaries that go after the bad guys. And sometimes, cancer cells develop ways of hiding from the immune system escaping that surveillance,” Garvin said. “But with CAR T-cell therapy, we’re combining the specificity and the affinity of a B cell with the cytotoxic fighting ability of a T cell.”

After patients are infused with the re-engineered T cells, they typically stay in the hospital for 2 weeks or longer, Garvin explained. At this time, it is crucial for nurses to monitor for major AEs, namely cytokine release syndrome and neurotoxicity.

“These can occur quickly while the patient is still inpatient and you’re taking care of them. They occur commonly and can be deadly,” Garvin said. 

Cytokine release syndrome (CRS) commonly occurs about 2 to 3 days after a CAR T-cell infusion, but can happen as early as a few hours after. It is caused when a high amount of cytokines — an immune substance – are released into the bloodstream.

Signs of CRS include fever, chills, and rapid heart rate.

“We take vital signs at least every 4 hours on the floor and more often if we feel like something is brewing,” Garvin said. “And then after you can see that hypoxia and hypotension. [We also] monitor labs every day.”

Severe or life-threatening CRS is treated with tocilizumab, and if that does not work, steroids may also be used.

Neurotoxicity can be any number of AEs originating from the nervous system, including delirium, dysphasia, word searching, encephalopathy, and seizures. The first sign is often a headache, and nurses should also look out for a “blank look” in patients’ eyes, Garvin said.

Garvin told the story of when she realized that a patient she had been treating for 2 weeks was experiencing neurotoxicity. “I walked into [her room] 1 morning and I handed her the pill cup, and she just stared at me like she’d never seen it before,” Garvin said. “She didn’t answer any of my questions; she didn’t look at me, and then she poured her pills down her shirt. That was the first time that [I noticed] that some [neurotoxicity] was beginning to brew.”

Risk factors for neurotoxicity — which usually happens about 4 to 6 days after CAR T-cell infusion – include higher disease burden and concurrent CRS.

Treatment for neurotoxicity is often supportive care and steroids may be administered, if needed. Garvin explained that neurotoxicity and CRS both have treatment guidelines depending on what specific type of CAR T-cell therapy the patient is receiving.

Ultimately, CAR T-cell therapy is a game-changer for blood cancer, but — like every other treatment – is not perfect and comes with risks.

“We do see relapse after treatment, we see death from [adverse events],” Garvin said. “I don’t want to oversell the treatment, but what I saw is that this treatment offers the promise of hope for patients for whom traditional chemotherapy didn’t work, and their prognosis is very poor.”

Garvin, K. CAR-T Therapy: Nursing Considerations. Presented at: 4

 Annual School of Nursing Oncology; July 31-August 1, 2020.

Nurses need to know the potentially life-threatening adverse events of CAR T-cell therapy.

CAR T-Cell Therapy: Promising, But Not Perfect

Despite many exciting advances in recent years, there are still aspects of melanoma treatment that need to be further studied and understood, said Grace Cherry, NP, a nurse practitioner at UCLA Health.

We need more research. Not everyone responds to the treatments. It's a lot better now compared to 10 years ago ... and a lot of our patients are living longer. That's the good news.

However, we still have patients that don't respond. So we need to continue with clinical trials so we can improve that and hopefully find a cure for our patients. Something that was never even thought of for many years for advanced melanoma, but now we're actually seeing patients that are responding and perhaps are even cured. So we want to improve on that.

Another unmet need, I would say, would be to learn more about the [adverse event] profiles of these medications. Some of them can be really toxic as far as immunotherapies. And is there a way that we can predict [adverse events]? Is there a way that we can treat them better so that toxicity doesn't have to stop the patient from getting treatment or doesn't decrease the quality of their life? We definitely need more studies on that too.

More for Melanoma: Nurse Discusses Unmet Needs

 mutations occurring in about 50% of patients with cutaneous melanoma

, the advent of BRAF/MEK inhibitors for this disease type have drastically improved outcomes in recent years, according to Grace Cherry, NP, MSN, RN, a hematology/oncology nurse practitioner at the Ronald Regan UCLA Medical Center.

Cherry discussed recent exciting advancements in the melanoma field at the 

 is a driver mutation,” Cherry said. “It’s like a light switch that signals cells to constantly grow…When it’s switched on, there’s no stopping that signal. It’s continuing to allow those tumors to grow rapidly. So, when given a BRAF/MEK inhibitor, it’s like turning off that switch.”

There are 3 different categories of BRAF/MEK inhibitors. And while there are some overlapping adverse events (AEs) between them, such as fatigue and nausea, each regimen has common AEs that nurses need to be aware of when treating their patients, according to Cherry. In particular, she noted the following:

dabrafenib (Tafinlar)/trametinib (Mekinist): fever

vemurafenib (Zelboraf)/cobimetinib (Cotellic): rash and photosensitivity

encorafeinb (Braftovi)/binimetinib (Mektovi): nausea

“Nurses are our frontline as far as giving these treatments and also in teaching our patients about side effects and detecting them,” Cherry said.

The first step in managing AEs from BRAF/MEK inhibition is confirming that patients have a 

 mutation. “If [patients] get these drugs and they’re 

 negative, they can have a paradoxical effect and make the tumor grow.”

Patients should then undergo a dermatological exam and an echocardiogram, since there is a small chance that they may have a cardiotoxicity. If the patient is experiencing blurred vision — which is rare – they should be sent to an ophthalmologist to check for ocular toxicity.

All patients experiencing AEs from their BRAF/MEK inhibition treatment should undergo labwork, where clinicians can monitor for elevated levels of liver enzymes, white blood cell counts, and rare AEs. Cherry also said that dose interruptions and dose reductions were very common in the clinical trials leading up to the drugs’ approvals.

“It’s warranted to do a dose reduction so [patients] can continue taking it on a continuous basis and sometimes they may discontinue if [toxicities] are really severe,” Cherry said.

Despite the landmark advances of BRAF/MEK inhibitors — as well as other agents, such as immunotherapy – in melanoma, there is still more work to be done

“Our patients have come a long way, compared to before BRAF/MEK inhibitors and immunotherapy came along, but we have a long way to go,” Cherry said. “Not everybody responds to [these agents] and we need to improve them.”

Cheng, et. al. Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. 

“Nurses are our frontline as far as giving these treatments and also in teaching our patients about side effects and detecting them,” Grace Cherry, NP, MSN, RN said.
 

Annual School of Nursing Oncology