Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 626

Anaemia may respond to the administration of erythroid‐stimulating agents (ESAs),^64‐66 which is generally first‐line therapy for mild anaemia. Response to ESA therapy is influenced by the MDS prognostic category, level of baseline serum EPO, and degree of transfusion dependence. Prognostic models have been developed to predict the response to ESA.⁶⁷ Lower levels of endogenous EPO, transfusion independence, and good‐risk MDS (based on IPSS classification) predict better response to ESA (Table 26.8).

Erythroid‐stimulating agents (ESAs) are commonly used to treat MDS patients to reduce transfusion requirements. The use of ESAs in MDS is supported by the American Society of Hematology (ASH), the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN).^68,69

Two large phase 3 studies investigated the role of ESA in treating anaemia in MDS patients.^70,71 Based on the results of these randomized controlled trials (RCTs), which showed a lower response rate for darbepoetin compared to epoetin‐alfa (14.7 versus 31.8%), EMA approved the use of the second one for this indication.

Table 26.8 Prognostic models for ESA response in MDS.

Source: Adaped from Buckstein et al.⁶⁷

Nordic score	ITACA score
Variables (1 point each):Transfusions >2 units per monthSerum erythropoietin >500 units I–1	Variables (1 point each):Transfusion independence (either < 1 unit every 8 weeks, over 16 weeks, or < 2 units of blood every 4 weeks)Erythropoietin (EPO) level <100 IU/LIPSS low‐risk
Score	Probability of response (%)	Score	Probability of response (%)
0	74	0	23
1	23	1	43
2	7	2	67
	3	85

Recombinant erythropoietin (EPO) is given subcutaneously one to three times weekly (starting at a dose of 450 IU/kg, up to 40,000 IU total dose). The choice of ESA regimen varies based on practitioner experience and/or patient preference. However, it’s better to treat with an ESA for at least 6–12 weeks before concluding that the therapy is ineffective. If the response is not adequate after 12 weeks, potential strategies include dose escalation, an increase in administration frequency, or the addition of a myeloid growth factor. There is no demonstrated benefit in crossing over from epoetin to darbepoetin or vice versa.

The combination of EPO and granulocyte‐colony stimulating factor (G‐CSF, 1–2 mg/kg subcutaneously weekly) has been shown to increase the haematocrit, and the number of circulating neutrophils and the combination may be synergistic. A predictive model for response can be utilized to identify patients who have a low, intermediate, or high probability of responding to ESAs and G‐CSF. The combination of G‐CSF and EPO appears to be particularly synergistic in patients with refractory anaemia with ring sideroblasts.^72–74

The risk for thrombosis should be evaluated before initiating ESAs. The risk for thrombosis in patients with MDS appears to be no higher than in age‐matched patients without MDS. Nevertheless, patients should be evaluated for a history of prior thromboembolism, heritable or acquired thrombophilic conditions, prolonged immobility, and other features.

Randomized trials have demonstrated an increased risk of thromboembolic complications and inferior survival in patients with solid tumours receiving ESAs.^75,76 Two independent retrospective analyses comparing MDS patients treated with ESAs with MDS patients not treated with ESAs have demonstrated a survival benefit for those treated with ESAs.^66,74 This benefit probably arises because they minimize transfusion and hence decrease iron overload. However, another retrospective study demonstrated no survival benefit for MDS patients treated with ESAs.⁷⁷ The Eastern Cooperative Oncology Group conducted a prospective randomized trial comparing the efficacy and long‐term safety of EPO with or without G‐CSF plus supportive care versus supportive care alone to treat anaemic patients with lower‐risk MDS.⁶⁵ With a median follow up of 5.8 years, no differences were found in the overall survival of patients in the EPO versus the supportive care arm or the incidence of transformation to acute myeloid leukaemia. Response rates in this trial were 36% in the EPO‐alone arm versus 9.6% in the supportive care arm. One patient developed a deep venous thrombosis in the EPO arm. Hence EPO can be effective in those patients with lower risk MDS, is considered safe and is not associated with an increased risk for mortality or leukaemic transformation.