Topics Alert

G-CSF or GM-CSF? Which Is the Safer Choice?

Date: June 22, 2024

Yesterday I sent out an Alert (# 102) that described the positive responses seen in NHL when Leukine (GM-CSF) was added to Rituxan. We have also discussed on this website the potential value of adding G-CSF (Neupogen and Neulasta: generic names – filgrastim and pegfilgrastim) to Rituxan therapy (the "RHK Protocol”). Unfortunately, we do not have formal, documented clinical trial results on either combination. The reported results of the combinations of Rituxan with these two growth factors in NHL also fail to compare the two growth factors head-to-head.

For some readers it has become a matter of strong-arming your local oncologist to add one of these growth factors to Rituxan therapy (hopefully you will also consider — and discuss with your doctor — the value of adding EGCG and fish oil capsules to the mix). In the absence of solid clinical data to help you make the decision, which growth factor should you chose?

G-CSF (Neupogen, Neulasta) is a more narrow gauge growth factor. It is supposed to influence only the granulocyte (neutrophil) creation. GM-CSF (Leukine), on the other hand, is a more broad spectrum growth factor in that it influences both granulocyte production as well as macrophage production. Growth factors are very potent agents, not to be used lightly. I hope you have read the latest article we published on this website, which reviewed the unexpectedly high and serious complications in combining Campath with G-CSF (Campath plus G-CSF). In that review we speculated on the possible mechanism of both early onset and delayed onset neutropenia with that combination. A while ago we also published a cautionary article titled The Dark Side of Epoetin. The links are below, if you want to refresh your memory.

Campath plus G-CSF;
The Dark Side of Epoetin;
The Difficult Case of the Round-Headed Kid.

So, is there any information out there to help us make a rational choice between GM-CSF and G-CSF? Not yet. There are little bits of the puzzle becoming clear, not yet the whole story. Below is an abstract that has one such piece of the puzzle, from the University of California. They compared 29 cancer patients who received G-CSF versus 27 patients who got GM-CSF. While both growth factors did the required job of recovery of neutrophil counts, GM-CSF seems to have been associated with quite a bit more adverse effects (febrile neutropenia, need for platelet and red blood cell transfusions, intravenous antibiotics use, even hospitalizations). Wow! That is quite a list. There are also reports that GM-CSF causes more bone pain than G-CSF; in fact patients cannot get GM-CSF in many European countries.

In the absence of definite published results on the “rewards” side of the balancing act, at this point I would say G-CSF is the winner as the growth factor with fewer “risks”. Of course, we are entirely willing and happy to turn ourselves around if new information says otherwise. There is no free lunch, but some lunches are more expensive than others, and you need to try and make sure you are getting bang for the buck.

Be well,

Chaya
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Abstract

Pharmacotherapy. 2024 Mar;25(3):372-8.

Effects of a formulary change from granulocyte colony-stimulating factor to granulocyte-macrophage colony-stimulating factor on outcomes in patients treated with myelosuppressive chemotherapy.

Wong SF, Chan HO.

Department of Pharmacy, University of California-Irvine Medical Center, Irvine, CA

STUDY OBJECTIVE: To evaluate the effects on efficacy and safety of a formulary change from granulocyte colony-stimulating factor (G-CSF) to granulocyte-macrophage CSF (GM-CSF).
DESIGN: Retrospective chart review.
SETTING: Single-center academic institution.
PATIENTS: Fifty-six patients aged 18 years or older with breast cancer, lung cancer, melanoma, Hodgkin's lymphoma, or non-Hodgkin's lymphoma who developed neutropenia within 4 weeks after treatment with myelosuppressive chemotherapy and who had been given five or more doses of CSF as primary or secondary prophylaxis from January 1995-March 2024. Twenty-nine patients treated before January 2024 were given G-CSF; after the formulary change in January 2024, 27 patients were primarily given GM-CSF.
MEASUREMENTS AND MAIN RESULTS: The primary efficacy end point was time to an absolute neutrophil count of 1.5x10(3)/mm3 or greater after treatment with CSF. Second and third efficacy end points, respectively, were frequency of febrile neutropenia and effect of CSF treatment on schedule and dose intensity of subsequent chemotherapy cycles. Primary and secondary safety end points, respectively, were frequency of adverse events and use of resources used to manage these events. The time to neutrophil recovery was similar with G-CSF and GM-CSF. Febrile neutropenia was more common in the patients given GM-CSF. Chemotherapy dose delays also were more common in patients treated with GM-CSF, as was the frequency of fever. Use of resources (platelet and red blood cell transfusions, intravenous antibiotics, and hospitalizations) was greater in the patients treated with GM-CSF.
CONCLUSION: The formulary change to GM-CSF was associated with a higher frequency of febrile neutropenia, resultant chemotherapy dose delays, more adverse events, and greater use of resources to manage the adverse events. These results suggest that G-CSF and GM-CSF are not therapeutically equivalent, with G-CSF having a superior safety and efficacy profile for the prevention of chemotherapy-induced neutropenic events.

PMID: 15843284
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