The use of r‐HuEpo in the treatment of anaemia related to myelodysplasia (MDS)

Abstract

One hundred and sixteen (1 16) anaemic patients with myelodysplastic syndromes (MDS) were treated with recombinant human erythropoietin (r-HuEpo) in an openlabel, multicentre, compassionate treatment trial: 100 patients received therapy for > 4 weeks and were evaluable for efficacy. The distribution of FAB subtypes was: 44RA. 40 RARS, eight RAEB, two RAEB-t, one CMML, and five not specified. Mean baseline haematocrit was 245%, and the mean prestudy transfusion requirement in the 12 weeks immediately prior to study entry was 6.5 units. r-HuEpo treatment was initiated at a dose of 150U/kg three times weekly, with dose escalations of SOU/kg monthly (up to 300U/kg 3 x/week) permitted if the haematocrit failed to rise. Response to therapy was defined as either an increase in haematocrit of > 6 percentage points over baseline, unrelated to transfusion, or a > SO% decrease in transfusion requirement in the last 3 months of study treatment, compared to the baseline period (12 weeks). By these criteria, 28% (28/100) of patients responded to r-HuEpo treatment. Overall, 86% (24/28) of patients responding to therapy had baseline Epo levels < 100mU/ml. Response rates by FAB subtype were: RA 39% (17/44), RARS 17.5% (7/40) andRAEB 12.5% (1/8). Additionally, a 54% (15/28) response rate was seen in RA patients with baseline EPo levels < 100mU/ml. Responses to therapy were durable and generally occurred at r-HuEpo doses of 150-200 U/ kg t.i.w. There were no reports of thrombosis, seizures or therapy-related hypertension. The data show that patients with MDS, especially those with the RA and RARS subtypes, can benefit from treatment with r-HuEpo. Those patients with baseline Epo levels < 100mU/ml were most likely to respond to therapy.

Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience

“…[26][27][28] Prognostic factors of response were largely similar to those previously published, including serum EPO less than 200 IU/L, absence of transfusion requirement, and IPSS low and int-1. 15,28 Some findings were, however, somewhat different from previously published literature. First, in RARS and RCMD-RS, response rates to rEPO alone were similar to those of rEPO with G-CSF, using both IWG 2000 and IWG 2006 criteria.…”

Aberrant immunophenotype of blasts in myelodysplastic syndromes is a clinically relevant biomarker in predicting response to growth factor treatment

“…2,11 Other reports state that Epo levels less than 100 U/L are indicative of a greater probability of response to Epo/G-CSF. 7,9,26 This cutoff level of 100 U/L appeared to be most discriminatory in our patient group: at an Epo level less than 100 U/L, 71% of patients (15/21) were responsive to Epo/G-CSF treatment, whereas 88% of the patients (22/25) with Epo levels greater than 100 U/L failed to respond. Thus, Epo levels greater than 100 U/L are highly associated with treatment failure (P Ͻ .001).…”

“…[3][4][5][6] Approximately 40% to 50% of anemic MDS patients demonstrate erythroid response to the combined administration of Epo and G-CSF. 2,[7][8][9][10][11] Response to growth factor treatment can be predicted by a model created on the basis of pretreatment serum Epo levels (Ͻ 100, 100-500, and Ͼ 500 U/L) and transfusion need (Ͻ or Ն 2 units per month). 8 This validated scoring system distinguishes 3 patient groups: 1 with a high probability of erythroid responses (74%), 1 intermediate (23%), and 1 poor (7%).…”

Clinical Use of Erythropoietic Stimulating Agents in Myelodysplastic Syndromes

“…Regarding thromboembolic events during ESA treatment, there are few published reports involving MDS patients [45][46][47], whereas in several meta-analyses of clinical trials with EPO, including several thousands of patients, no episodes of hypertension, seizures, or cardiovascular events directly resulting from the growth factor were reported [25,39,48,49]. In contrast, several studies indicated longer survival times in MDS patients responding to therapy with ESAs [26] (50 and 51).…”