Yelena Shames, MSA, ACNP-BC, CNRN, argues that frequent hematologic evaluations may not always be warranted with immune checkpoint inhibitors.
Frequent hematologic evaluations, including blood draws, to assess abnormal laboratory values may not be necessary for patients receiving immune checkpoint inhibitors (ICIs), such as pembrolizumab (Keytruda), according to Yelena Shames,MSA, ACNP-BC, CNRN.
Data presented at the 48th Annual Oncology Nursing Society showed that patients (n = 183) who were given pembrolizumab received 778 doses and of those, only 15 doses were delayed or discontinued because of laboratory abnormalities.
Grade 3 or 4 adverse events occurred in 8 of the 15 patients, several patients experienced hyponatremia ranging from grade 1 to 3 in severity, and 6 patients permanently discontinued treatment. AST/ALT/bilirubin increase (n = 7) as well as amylase/lipase (n = 4) and platelet count increases (n = 3) were the most common laboratory abnormalities. Most of these abnormalities were identified via chemistry evaluation rather than hematologic evaluation. Investigators said additional research is needed with a larger sample size of patients who are ICI-naïve as prior ICI treatment may have contributed to recurrence of laboratory abnormalities.
In an interview with Oncology Nursing News®, Shames, the clinical trials nurse leader at Memorial Sloan Kettering Cancer Center, discussed the process behind assessing dose delays in the study as well as implications of the data.
Oncology Nursing News: What observations led to the initiation of this project?
Shames: [In the] initial phases [of] clinical trials, laboratory monitoring frequency, as well as management of abnormal laboratory values, were based on [an] individual protocol. It was not based on any American Society of Clinical Oncology or National Comprehensive Cancer Network guidance: there were no clear instructions for the providers [on] what needs to be done should patients develop clinically significant laboratory abnormalities.
Ironically, when we took care of patients in our clinic, our observations were that clinically significant laboratory abnormalities were rarely contributing to dose delays by itself because, a lot of times, they were concurrent with other clinical toxicities. We hypothesized that in patients who tolerated initial doses of ICIs uneventfully, the frequency of laboratory abnormalities could be reconsidered, as well as the pathology between the clinically significant laboratory abnormalities. Dose delays or dose discontinuations could also be reconsidered.
Could you briefly describe the methodology of the research?
We wrote a proposal to our local institutional review board. After receiving approval for that proposal, we performed a retrospective review of 211 records of patient history [for those treated with] commercial pembrolizumab. We performed descriptive statistical analyses looking into demographics, frequency of some of the laboratory abnormalities/other data, as well as central trends using ranges, means, and median numbers to describe our information and results.
Did any findings from this research surprise you?
Yes, we had the feeling that laboratory abnormality alone rarely contributed to dose delays, but to see the actual number to what degree they have contributed to dose delays was quite surprising. Out of 211 records that we reviewed, 183 patients were evaluable for the primary and secondary end points. Out of 183 patients, only 78 patients experienced dose delays during treatment. Further, out of 78 patients, only 15 doses were held due to clinically significant laboratory abnormalities.
When we looked further into the number of doses that were delayed in relation to total number of doses of pembrolizumab that were administered within the window, the number was very surprising; 0.19% of dose delays [were] attributed to clinically significant laboratory abnormalities.
Our second “aha” moment was a patient who was diagnosed with end-stage renal disease prior to his diagnosis of melanoma. He had undergone cadaveric renal transplant surgery prior to being treated for his cancer [and] was offered pembrolizumab monotherapy [but] after his first dose he developed acute renal rejection of his allograft. After careful discussion of risks, benefits, and alternatives, that patient opted to proceed with hemodialysis and continue with pembrolizumab. [He] was able to tolerate a total of 17 doses of pembrolizumab which raises another question of [what] patients with different autoimmune diseases or patients with immunosuppressive therapies, [and] their ability to tolerate ICIs [is].
What are the overall implications of this research for oncology nursing?
The implications are large because as nurses or advanced practice nurses we always advocate for our patients and to know that patients may not necessarily have to undergo all the blood draws is probably one of the largest points of nursing advocacy. It would improve patient’s experience. Financially it also has implications in terms of reducing financial burdens on patients [with] unnecessary blood draws which may or may not be reimbursed by insurance companies.
For the institutions, it also has implications both on clinic wait times associated with physicians or advanced practice providers having to wait for results to come back prior to determination of clearing patients for treatment. [Additionally, there are the] financial implications of having facility fees and everything else associated with blood draws.
What continues to be one of the biggest challenges in optimizing ICI care?
In the initial phase clinical trials a lot of patient populations were excluded from participation [because of safety concerns]—I do not think we have any specific data related to using ICIs in the geriatric patient population. In our practice most of the time we would offer monotherapy [with] PD-1 or PD-L1 ICIs rather than combination immunotherapy [out of] the concern of how elderly patients may tolerate ICIs, but I don’t think this is data driven. We also do not have a lot of knowledge on how patients with preexisting autoimmune diseases tolerate ICIs because they were excluded for the most part as well as patients who received immunosuppressive therapies for management of their preexisting conditions—for example, our patient who received renal allograft.
Another group of patients that we would like to explore further [is] patients who were treated with immunosuppressive therapies such as steroids or secondary immunosuppression [agents such as] infliximab or CellCept for management of their ICI related toxicities. [There’s] an opportunity for a lot of research for the future.
Shames Y, Errante M, and Prempeh-Keteku N. To treat or not to treat? Evaluating abnormal laboratory values in patients receiving immune-checkpoint inhibitors. Poster presented at: 48th Annual Oncology Nursing Society Congress; April 26-30, 2023; San Antonio, TX. Accessed May 15, 2023. https://ons.confex.com/ons/2023/rs/eposterview.cgi?eposterid=2784