Dr. Bishal Gyawali and Dr. Tessa Cigler share the new, comprehensive, evidence-based update of the ASCO guideline on the use of hematopoietic colony-stimulating factors in patients with cancer. They discuss recommendations on primary prophylaxis, secondary prophylaxis, and treatment of febrile neutropenia along with stem cell mobilization, efficacy, safety, duration, dosing, and administration of CSFs – including biosimilars. They highlight where it is appropriate to use a CSF, and importantly, when not to use a CSF. They touch on the significance of individual patient considerations and cost implications, and future work to refine the risk factors for the development of complications of febrile neutropenia. Read the full guideline, "White Blood Cell Growth Factors: ASCO Guideline Update" at www.asco.org/supportive-care-guidelines TRANSCRIPT This guideline, clinical tools and resources are available at www.asco.org/supportive-care-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-25-02938 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Bishal Gyawali from Queen's University in Kingston, Ontario, Canada, and Dr. Tessa Cigler from Weill Cornell Medicine in New York, New York, co-chairs on "White Blood Cell Growth Factors: ASCO Guideline Update." Thank you for being here today, Dr. Gyawali and Dr. Cigler. Dr. Bishal Gyawali: Thank you very much for having me. It's a pleasure. Dr. Tessa Cigler: Hi there. Nice to be here as well. Brittany Harvey: Great. And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Cigler and Dr. Gyawali, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then I'd like to dive into the guideline that we're here today to talk about. So first, what prompted an update to this guideline on the use of hematopoietic colony-stimulating factors in patients with cancer, and what is the scope of this updated guideline? Dr. Bishal Gyawali: The last version of the guidelines from ASCO on this topic was back in 2015, so it has been more than a decade since ASCO had a guideline on the use of G-CSF in patients with cancer receiving treatment. So it was due for an update because there has been a lot more evidence based on not necessarily new drugs, but evidence for proper timing of these agents and the duration of these agents, as well as there have been a lot of new biosimilars, and there are questions about are these biosimilars equivalent or how do we choose among these different options. One is that content of the evidence that has evolved over time in the last decade, but also I think the last time we had these guidelines, the ASCO guidelines were not incorporated to have those evidence GRADE tables. So the quality of the ASCO guidelines itself has evolved over the years, so we wanted to have a new version of the guideline that includes not only the new evidence, but also contains those evidence GRADE tables that will help to quantify the benefits. And so I think it was high time, and even more than that, the newer ASCO guidelines for any guideline, they also include considerations of cost, access, equity, and all these factors that were not included in the previous version of the guideline. So I think it's only natural that with time the guideline should also evolve. Dr. Tessa Cigler: I agree completely, and just as a framework, as we all know, neutropenia and its complications, including febrile neutropenia and infections, are still an important toxicity of many myelosuppressive chemotherapies. And these neutropenic complications do require prompt evaluation and treatment and often hospitalization, and we know that hematopoietic colony-stimulating factors, which I'm going to refer to as growth factors, can reduce the duration and severity of neutropenia and the risk of febrile neutropenia, so it remains an important topic in the practice of clinical oncology. Brittany Harvey: Absolutely. It's an important topic for both clinicians and for patients who are receiving treatment for their cancer. And as you said, there was a substantial amount of literature to review here and updating everything to be in line with the GRADE evidence rating system, so there was a lot of work that you both put into this. So then next, I'd like to review the key recommendations of this guideline by clinical question. So first, what factors did the expert panel identify that should influence the decision to administer primary prophylaxis of febrile neutropenia with a CSF? Dr. Bishal Gyawali: Yeah, so I think that constitutes one of the most important recommendations in our guidelines about primary prophylaxis with G-CSF. And this is important because not only it's about when to use it, it's also about when not to use it, as in the ASCO "Choosing Wisely" campaign has also made some recommendations about this. So our guideline recommendations are also aligned with that. So first of all, we recommend that primary prophylaxis with G-CSF is recommended when the risk of febrile neutropenia because of the chemotherapy regimen is equal to or more than 20% unless an alternative chemotherapy regimen with comparable efficacy and safety that does not need G-CSF is available. And the quality of evidence to make this recommendation is high, so we give a strong strength of recommendation for this. Having said that, even for patients where the risk of febrile neutropenia is not necessarily 20%, it's a little lower, but because of other patient-related factors, the patient is at a higher risk of complications from febrile neutropenia, such as age, comorbidities, and other factors, in such case primary prophylaxis with G-CSF should be offered. And we also make a recommendation that if G-CSF is not affordable or available, then antibiotic prophylaxis can also be offered, but the evidence quality for this is low, and the strength of recommendation is very conditional. A couple of things to highlight here would be that, I think Dr. Cigler can attest to that, we ran into lots of problems about finding the data for the evidence base to say what are the patient-related factors that actually make them at a higher risk of febrile neutropenia, you know, like how did that 20% benchmark come about? Why 20%? Or when we say even if it's less than 20%, if based on other comorbidities, if the risk is higher, we tried to dig into that evidence. For example, we're talking about our "Box 1" in the guideline, what is the evidence for each item we have included under that "Box 1"? And we tried to do a lot of search to find the evidence for that, and some of them do have strong evidence, and that will tie into our future research ideas as well. And some of them actually don't have such solid evidence too, so that was one of the reasons why we ran into lots of problems about how do we quantify whether someone is at a high risk of febrile neutropenia and where that 20% benchmark comes from. Dr. Tessa Cigler: And definitely, because there's not very clear data, our guidelines definitely leave room for physician discretion in all these situations. Brittany Harvey: Absolutely. I find that in a lot of these guidelines the key point is that there's a lot of shared decision-making with patients after talking through what risk factors they may have and what is best for them in their individual clinical scenario. So then moving on to secondary prophylaxis, what factors did the expert panel identify that should influence the decision to administer secondary prophylaxis of febrile neutropenia with a CSF? Dr. Tessa Cigler: So for patients who've already experienced a neutropenic complication from a previous cycle of chemotherapy, the question is which patients should then receive prophylactic G-CSF for subsequent cycles of chemotherapy. And without a lot of evidence again to guide us, the panel really felt strongly that secondary prophylaxis should be used when a treatment delay or when a reduced dose of chemotherapy would be thought to compromise cure rates or survival outcomes. We do note that in many situations, certainly a dose reduction or a delay would be a very reasonable alternative or an additional strategy to G-CSF administration. Dr. Bishal Gyawali: Yeah, I think it's more like if there is going to be compromise in outcomes without using G-CSF, as in if we can't maintain the dose intensity and that's going to lead to inferior outcomes, then we should. But if we can reduce the dose intensity and treatment frequency and still have the same outcomes, then I guess in simple words, we're just trying to say use it when it's absolutely needed, or you can also look into other alternatives that might not need G-CSF but you could maintain the same outcomes. Brittany Harvey: Understood. It's helpful to review those options for clinicians and showing that there's not just one way to address potential neutropenic complications for later cycles of chemotherapy. So then following those recommendations for prophylaxis, what does the expert panel recommend regarding CSFs for the treatment of febrile neutropenia? Dr. Bishal Gyawali: This is an important question because this ties strongly with the "Choosing Wisely" campaign. In other w
