{'fraction_non_alphanumeric': 0.04067796610169491, 'fraction_numerical': 0.02288135593220339, 'mean_word_length': 4.661870503597123, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
CERA (Continuous Erythropoiesis Receptor Activator) in patients with multiple myeloma: An exploratory phase I-II dose escalation study.

6552 Background: Preclinical/phase I studies indicate that CERA has distinct properties that point to a unique mechanism of action and potent erythropoietic activity both in magnitude and duration of action. This study aimed to identify a suitable CERA dose range for further clinical testing in patients with cancer-related anemia.


METHODS
This was an open-label, exploratory, multicenter, dose-escalation study in patients (≥18 y) with multiple myeloma (receiving chemotherapy) and with anemia (Hb ≤11 g/dL). Patients (n=64, in groups of 8-10) received CERA SC once every 3 wk for 6 wk (core period), with an optional extension to 12 wk. Initially patients were randomized to receive doses of 2.0, 3.5 or 5.0 μg/kg. Following review of efficacy and safety data, additional patients were assigned sequentially to doses of 6.5 and 1.0 μg/kg, then 8.0 and 4.2 μg/kg. Demographics were similar in all subgroups of patients. The primary efficacy variable was Hb change from baseline to end of initial treatment (completion of the core study period, transfusion or dose change) as assessed by regression analysis. Pharmacokinetic (PK) parameters were assessed throughout.


RESULTS
CERA produced a rapid, clinically relevant, dose-related increase in Hb with a trend for a plateau in response at doses of 5.0-8.0 μg/kg. During the core period, CERA 3.5-8.0 μg/kg produced a mean Hb increase of 1.6-2.3 g/dL; 50-62.5% of patients had a response of ≥2 g/dL; levels were maintained or improved during the following 12 wk. PK measurements will be reported. AEs attributed to CERA were rare (4 hypertension, 1 pyrexia) during the core period. There were no unusual clinical and laboratory measurements. No evidence of antibody development was observed.


CONCLUSIONS
In patients with multiple myeloma, CERA administered once every 3 wk was generally well tolerated and produced a rapid and sustained increase in Hb, which was consistent with its prolonged serum half-life. The long dosing interval of CERA may enable administration on the same dosing schedule as chemotherapy agents and offers flexibility and convenience in the treatment of patients with cancer-related anemia. No significant financial relationships to disclose.