Joy Anderson, MSN, RN, OCN, is the Clinical Operations Manager for medical oncology and radiation oncology at Saint Agnes Cancer Institute, Baltimore, Maryland, and Carole Miller, MD, is Section Chief in this eight-person medical oncology/hematology practice. Recently, they hosted an Institute for Clinical Immuno-oncology (ICLIO) Visting Experts workshop to accelerate their learning about managing patients being treated with immuno-oncology (I-O) agents.
The cancer team at Saint Agnes considers itself an academically focused community hospital program, having four standing tumor boards a week, and being accredited by several organizations to provide cancer care (i.e., American College of Surgeons Commission on Cancer, American Society of Clinical Oncology Quality Oncology Practice Initiative, American College of Radiology).
Despite these credentials, Miller and Anderson wanted to ensure that they build as much expertise in immuno-oncology as possible as a result of daily challenges that their institution faces, including but not limited to recognizing and managing immune-related adverse events (irAEs), understanding the differences between chemotherapy and I-O with regards to mechanisms of action, and, generally, other nuances and concerns that arise as a result of the ever-increasing availability of new I-O agent(s), new indications, and combination I-O therapies.
Although I-O treatment is an exciting area of oncology for Miller and her team, differences across guideline recommendations can compound the challenge of using these therapies in practice. In addition, the number of patients being treated with I-O agents at Saint Agnes is increasing rapidly, doubling within the last 10 months. This rapid increase is good news for patients, but requires that staff get up to speed quickly on how to use these immunotherapies effectively, understanding how a tumor responds to these immunotherapies, and recognizing irAEs which can differ significantly from typical side effects observed with chemotherapy agents.
"These drugs have incredible power, but also have a completely new class of toxicities. Anything can happen with these drugs. And so, it’s important to get any extra help we can to make sure we’re, number one, doing the best for our patients, and number two, educating our providers." –Carole Miller, MD
To build on their experience and gain more I-O education, Miller and Anderson hosted an ICLIO Visiting Experts workshop on May 23, 2017 where they shared some of their strategies for managing resources to accommodate I-O in their cancer center. Through moderated discussion and sessions, the following ICLIO faculty experts shared tools and tips for recognizing and treating side effects and irAEs: Jarushka Naidoo MBBCh; Joanne Riemer RN, BSN; Jeff Liticker RPh, PharmD, BCOP; Nicky Dozier, PharmD, and Jake Guinto, PhD.
Saint Agnes currently has two open I-O drug trials for melanoma: a basket protocol that has multiple different phase one endpoints, and a myeloma trial with nivolumab. Given the growth of the I-O program at Saint Agnes, it has been challenging for Anderson—whose role as Operations Manager involves physician management, quality assurance/quality improvement, educational materials, staffing, and budget—to ensure sufficient coverage across the oncology program (i.e., both medical oncology and I-O).
The Saint Agnes solution to this resourcing issue has been to cohort patients being treated with I-O therapies into a Friday I-O infusion clinic that is staffed by a core group of nurses. Having a core group strategy has enabled Saint Agnes to expand nursing expertise and ensure that nurses get to know patients "so they can really see a difference from one week, one visit to the next." Dr. Miller believes this strategy has helped their nurses to develop a deep appreciation of the nuances associated with immune-related adverse events (irAEs).
"I-O patients are 'different.' They’re not getting cycles of chemotherapy. They bring their own set of issues, and so we decided to strategically develop core nursing expertise." – Carole Miller, MD
The workshop further deepened this appreciation and showcased practical and process recommendations that Saint Agnes staff felt they could incorporate into their routine.
For both Anderson and Miller, the question of recognizing atypical toxicities resulting from I-O therapy was an especially important area covered by the workshop. In addition to being exposed to clinical pearls about how to recognize, monitor, and treat different irAEs (e.g., using decreases in exercise pulse oximetry as a risk marker for pneumonitis), Dr. Miller praised the workshop for covering the pathophysiology and patterns of pneumonitis, as well as new rheumatologic symptoms, such as arthritis and myopathies.
Anderson appreciated the "all-encompassing" range of content presented in the workshop and felt it touched on many different subjects that were especially helpful for nurses, such as how I-O therapies work with the different cells of the immune system and the management of irAEs, including the importance of educating emergency room staff on the differences between managing side effects for chemotherapy patients versus those being treated with an I-O agent.
"It really helped us to understand the actions of the medicines and how they work with the T-cells, B-cells, and antigens. Dr. Naidoo obviously knew there would be non-physicians in the room. She was able to explain the immune response and the use of I-O checkpoint inhibitors in a way we could understand.
And side effects are treated differently, so it’s concerning when our patients are brought into the emergency room. We were very grateful to get the [patient I-O identity] card that the patients can carry from ICLIO. That will definitely help. [It’s also challenging] to make sure other areas that may be treating those patients from time to time understand the differences in chemotherapy and autoimmune system and the side effects."
Faculty also focused on different patterns of progression and of pneumonitis, supported by images that Dr. Miller thought provided a very practical resource to help clinicians build familiarity with, and recognize, pseudoprogression.
The question of whether to hold treatment when a patient is experiencing an irAE and what the risk might be of withholding that treatment was discussed during the workshop. As Dr. Miller observed, checkpoint inhibitors have a longer half-life and distinct mechanisms of action, so that the therapeutic effect lasts long after the therapy is out of the body. This characteristic ensures that clinicans can withhold treatment and evaluate toxicity.
Nonetheless, for practicing clinicians, there is a difference between reading about this strategy in a journal and learning from experts with firsthand experience. As Miller noted, “It was nice to have someone who does this a lot tell you, ‘It’s okay if you’re not sure if the diarrhea is on its way up, or how the colitis is developing. Hold a week. It’s okay, and then you can restart.’”
An ongoing goal for the cancer care team is how best to deliver multidisciplinary I-O care. To this end, Saint Agnes has developed champions in pulmonary, cardiology, and endocrinology, and is trying to get them to work on developing a "dream team." The workshop has helped them think more about how best to do this, too. Dr. Miller noted:
"When we focused originally on our I-O dream team, it was basically what we needed within the cancer center, and what they talked about and what the sort of interesting takeaway is that you need to not just look at the cancer center, but you need to engage people outside the cancer center."
Miller is under no illusions about the challenges ahead to develop a dream team in a community cancer center. But Saint Agnes already has an onco-cardiologist who is interested in the cardiac manifestations of oncology, and Miller’s team works closely with clinicians in pulmonary, endocrinology, and gastrointestinal medicine. She believes these relationships offer a platform for initial education that can be expanded to include others who are interested in I-O. One education model she already has in mind is an ICLIO Case Study, which, she will use as a "stepping stone to get our dream team together."
Going forward, there are persistent obstacles in I-O that are going to be especially challenging for Saint Agnes to address. For Anderson, reimbursement remains a challenge.
"The reimbursement piece is tough. The drugs are expensive, and we’re in an area where there are disparities, and people have lots of financial issues such as; transportation, paying for housing and food, etc. It’s not easy for them to pay their copay and other out of pocket expenses. Those are huge challenges, the financial piece."
As a way to navigate the financial challenges, staff currently search for assistance by helping patients find insurance coverage, patient assistance programs and grants. Saint Agnes also has a charity care program for patients who meet the qualifications.
Regardless, Anderson observed, Saint Agnes is "certainly not not going to treat people." The Pharmacy Connection was one of the resources shared during the workshop that she felt could have immediate impact on how she and her nursing team seek patient assistance funds. This website, created by Virginia Health Care Foundation, is a tool that staff can use to enroll their patients in and determine their eligibility for pharmaceutical Patient Assistance Programs (PAP).
The value to Saint Agnes staff of such a resource will be to minimize data entry (and therefore precious clinical time), since the tool automatically sends a patient’s information to multiple patient assistance sites, tracks the status of applications, and streamlines paperwork. For Dr. Miller, a key challenge moving forward will be the anticipated financial and clinical toxicities with combination I-O therapies.
"They may be more effective, but the risk is higher. We have to make sure that we understand when are the risks appropriate, and do we know that we’re not accepting too much toxicity for the benefits? At this point, therapy is palliative and therefore the questions of doublet upfront versus addition of second drug depending on initial response needs to be examined in clinical trials as it is clear that toxicity is greater with combination therapy. Additionally, there needs to be serious discussion about the costs of these drugs especially in combination therapy."
The issue of possible overtreatment also remains a key question for Miller, especially in relation to the question of whether to treat to progression or toxicity. This is likely to be subject to investigation in future studies, since there are patients who have stopped therapy, but may continue to be in a stable response for years.
The moderated discussion helped keep participants on focus during the workshop, and address the issues identified by Miller and Anderson. Other workshop participants agreed that having experts on-site who were open to questions was key to learning. Content was conveniently divided into sections, and issues were tackled from a multidisciplinary perspective—an important strategy to ensure dialogue within and across disciplines and staff, such as social work, financial advocacy, infusion/oncology nurses, pharmacists, administrators, and physicians. As Miller observed, the combination of targeted content and an engaging format created a win-win for their program.
"The program was actually better than we even expected. It exceeded our expectations. We had really good discussions, and everyone felt that it was at an appropriate level that kept everyone’s interest. . . If you really want to sort of consolidate your ability to provide this program or this type of I-O therapy, it’s a win-win for your program."
–>Carole Miller, MD
Last review conducted on 10/08/2019.
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