Recombinant Granulocyte-Macrophage Colony-Stimulating Factor (rGM-CSF)

Summary

Synopsis

Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) expedites neutrophil recovery in cancer patients receiving chemotherapy with or without autologous bone marrow transplant (ABMT). The limited cost analyses available in patients undergoing ABMT support a cost reduction of about 25 to 35% with rGM-CSF therapy, relative to placebo, generated primarily by decreases of 20 to 30% in hospitalisation costs reflecting reductions in length of hospitalisation. Results of 1 trial show equivalent cost savings of 40% versus placebo with either rGM-CSF or recombinant granulocyte colony-stimulating factor (rG-CSF) in patients with chemotherapy-induced febrile neutropenia. Whether reduced infection rates seen with rGM-CSF may lessen costs of antimicrobial therapy is undetermined; however, a 16% decrease in this cost factor was reported in 1 evaluation of high dose chemotherapy with ABMT. No analyses have assessed the cost effectiveness of rGM-CSF as prophylaxis in patients receiving chemotherapy.

Survival rates have increased in patients treated with rGM-CSF after bone marrow graft failure. In contrast, with the exception of one small trial, improvements in mortality or relapse rates have not occurred with rGM-CSF used prophylactically with chemotherapy, despite favourable effects on neutrophil recovery and facilitation of dose-intensified chemotherapy regimens. Similarly, survival has not increased in patients undergoing ABMT. The long term economic impact of rGM-CSF in these indications is thus unknown.

Other factors predicted to produce modest cost savings include possible reductions in expenditure related to treating mucositis, and lowered transfusion requirements in some patients. Whether rGM-CSF may provide benefits in other areas that can be expressed in economic terms, such as quality of life, also remains to be established. On the whole, rGM-CSF has a good tolerability profile, obviating the need for costly monitoring procedures. Like other expensive biotechnology products, its cost effectiveness will be aided by implementation of appropriate prescribing techniques and protocols to minimise wastage.

Thus, at present rGM-CSF therapy appears to offer a means of reducing hospitalisation costs, itand therefore a substantial component of treatment expenditure, in patients undergoing ABMT or with chemotherapy-induced febrile neutropenia.

Disease Considerations

Neutropenia is a deleterious consequence of myelosuppressive chemotherapy with or without autologous bone marrow transplant (ABMT). Persistent neutropenia, lasting approximately 15 to 30 days in patients undergoing ABMT and up to 2 weeks after high dose chemotherapy, predisposes patients to a higher risk of infection (febrile neutropenia) and jeopardises optimal delivery of chemotherapy regimens.

Hospitalisation costs comprise the largest expenditure associated with neutropenia management. If neutropenia is severe, care in specialised isolation units will increase the “hotel” costs. Acquisition and administration costs of broad-spectrum empirical intravenous antimicrobial therapy, needed to treat immunodepressed patients infected with Gram-positive and Gram-negative organisms, represent a significant cost estimated to range from approximately $US3850 to more than $US10 000, depending on the regimen prescribed and cost factors taken into account. Requirements in some patients for drugs active against viral, fungal, anaerobic and resistant organisms add further expense.

Factors Influencing Pharmacoeconomic Assessment of rGM-CSF

In conjunction with other colony-stimulating factors, native GM-CSF influences differentiation and maturation of multiple cell lineages, and is crucial for development of the granulocyte-macrophage lineage. rGM-CSF shortens the neutropenic period in patients undergoing chemotherapy with or without ABMT by up to 2 weeks. In patients undergoing ABMT, this has translated into a reduction in duration of hospitalisation, which represents the main area of prospective cost savings. Trends toward decreased infection rates and thus reduced need for antimicrobial therapy demonstrated in some studies may also contribute to cost savings.

Prophylactic adjuvant therapy with rGM-CSF permits delivery of chemotherapy regimens on time and, frequently, in dose-intensified regimens. Such an approach may entail higher initial costs because of chemotherapy-related expenses, including dose-limiting nonhaematological toxicities. Theoretically, however, costs may be recouped over the longer term through reduced numbers of hospital visits.

Decreases in rates of mucositis and transfusion requirements noted in some patients receiving rGM-CSF may contribute a modest cost saving. However, there have been no clear and consistent indications of improvements in relapse and survival rates with rGM-CSF therapy in clinical trials in patients receiving chemotherapy with or without bone marrow transplant, nor has quality of life amongst survivors been surveyed.

Enhanced bone marrow transplant outcome in patients treated with rGM-CSF after failure of engraftment has, however, improved survival. Facilitation of progenitor cell harvest for use in engraftment may in theory provide cost reductions, since the duration of hospitalisation tends to be longer in such patients. The economic implications of these effects of rGM-CSF have yet to be formally considered.

Expenditure incurred by acquisition cost and administration (pharmaceutical and nursing time) of rGM-CSF may be reduced by use of subcutaneous rather than intravenous injection methods, and by implementing dosage schedules and protocols to minimise wastage. Laboratory monitoring during rGM-CSF therapy is unlikely to consume significant additional resources, as oncology patients are routinely assessed during chemotherapy and bone marrow transplant. rGM-CSF, with its good tolerability profile, is relatively free of serious unwanted effects likely to require cost-intensive treatment. An exception may be the infrequent development (in < 1 % of patients) of pleural or pericardial effusions in susceptible patients with pre-existing conditions.

Cost Analyses

Of the few available analyses, 2 may be considered formal evaluations. A US report in 24 patients with relapsed Hodgkin’s disease undergoing ABMT describes a reduction of 36% for molgramostim in median total charges relative to placebo, arising primarily from a 30% reduction in hospital room charges due to shortened neutropenic periods and thus fewer days spent in hospital. These results are similar to those of another US study documenting a 21% reduction in initial hospitalisation charges in 40 patients with lymphoma administered sargramostim. Data from briefly reported and less well-designed evaluations using molgramostim support savings with rGM-CSF of about 25% in total costs expended in this clinical setting. A significant reduction of 16% for specific antimicrobial charges was observed in 1 study.

When used as intervention in patients with chemotherapy-induced febrile neutropenia, rGM-CSF resembles recombinant granulocyte colony-stimulating factor (rG-CSF) in clinical efficacy and tolerability, a finding reflected in the identical reductions of 40% in total costs achieved with both drugs in an abstract of a Spanish placebo-controlled cost analysis trial. The cost effectiveness of rGM-CSF used prophylactically in patients receiving chemotherapy has not been evaluated.