Guidelines for Managing Chemo-Induced Myelosuppression in ES-SCLC

Charu Aggarwal, MD, MPH: What are the recommendations from the NCCN [National Cancer Comprehensive Network] with regard to management of chemotherapy-induced myelosuppression? We look at neutropenia, and I did discuss with you briefly earlier that we think in terms of what the risk is of febrile neutropenia in a patient who’s receiving chemotherapy. And we think about the chemotherapy regimens as either high risk for febrile neutropenia, intermediate risk, or low risk. For my high-risk regimens, I often will come in with prophylactic growth factor support, which may be short-acting growth factor support, but it’s not feasible because it has to be dosed daily subcutaneously. Or I would use a long-acting growth factor support like pegfilgrastim that could either be administered as an on-site body injector, so patients don’t have to come in the next day to receive it, or they come in the next day, depending on insurance approvals, etc.

Usually for anemia, if hemoglobin is less than 11 [g/dL], I would observe. If it’s less than 8 [g/dL], I usually proceed with a blood transfusion. I don’t use erythropoietin stimulating agents [ESAs], and the reason for that is because there is a black box warning, at least in the curative intent setting, that ESAshave been shown to accelerate oncogenesis. And since there is this black box warning in the adjuvant setting, I tend to stay away from it even in the metastatic setting. For platelets I will hold if they’re less than 100,000 [per μL], and I look for any additional underlying causes that may be causing thrombocytopenia.

Most recently, we also saw that trilaciclib, which is a CDK4/6 inhibitor, can support bone marrow and reduce myelosuppression, especially in patients who receive chemotherapy or chemoimmunotherapy for extensive-stage small cell lung cancer. It is included in the NCCN guidelines, but as a category 2B recommendation. It does involve a few extra steps in terms of its use, so I haven’t adopted it into my practice, but it certainly offers a new intriguing way to manage myelosuppression.

Jared Weiss, MD: The NCCN provides us guidance on how to manage and prevent myelosuppressive events. Of note, there’s the baseline guidance and then modified guidance during COVID-19. The baseline guidance is that for patients with at least a 20% risk of febrile neutropenia to give primary prophylactic filgrastim or pegfilgrastim. For patients at intermediate risk, which they define as a 10% to 20% risk of febrile neutropenia, they say that you can consider this prophylaxis based on patient-specific risk factors, such as prior chemotherapy or radiotherapy, persistent neutropenia, known bone marrow involvement with the cancer, recent surgery, liver or renal dysfunction or age of over 55 years. And for patients with low febrile neutropenia risk, defined as less than 10%, we shouldn’t do it. NCCN says that for secondary prophylaxis, if pegfilgrastim or filgrastim were not used as primary prophylaxis in a prior cycle, you can add them. If they were used, you should then consider dose reduction or a change in treatment. Interestingly, for treatment of febrile neutropenia, NCCN is mostly negative on this. First, if prophylactic pegfilgrastim or filgrastim had been used, they say there’s no purpose in doing anything further. And if there hadn’t been, you're only supposed to do it if the patient is at high risk for an infection-related complication.

Now in the COVID-19 era, the NCCN has liberalized guidance and they’ve expanded the primary prophylactic use of G-CSF [granulocyte colony-stimulating factor]. They’ve changed the threshold that for the intermediate-risk patients, they're now recommending the use of G-CSF. For chemotherapy-induced anemia, interestingly NCCN largely defers to the American Association of Blood Banks. And they want you to consider how symptomatic the patient is as well as their hemoglobin threshold. In the era of COVID-19, NCCN recommends reducing that threshold to only transfuse for hemoglobin less than 7 [g/dL]. For thrombocytopenia, again, the threshold has been lowered in the COVID-19 era for patients who are either bleeding, or you can even go far lower, they went all the way down to 10, and said you could consider thrombopoietin here to prevent the need for platelet transfusions. For anemia, I would call these guidelines controversial. Patients with cancer will start feeling more fatigued if hemoglobin’s below normal, and at least in the old ESA literature, feel better when you get their hemoglobin up. Of course, we all know the ESA story. They were overused, they led to adverse events, and they now have a black box warning. But those historic data do show us that if you get a patient down to a hemoglobin of 7 [g/dL], they’re going to feel quite lousy. And I will publicly confess that in my practice, I transfuse more liberally than that for reasons of quality of life of our patients.

Transcript edited for clarity.