An analysis of baseline AAG levels in 45 patients revealed that patients with low AAG remained on study longer than did those with high AAG in both cohort one (3.4 months vs. 1.7 months) and cohort two (6.2 months vs. 1.6 months). Moreover, 24% of low-AAG patients on monotherapy and 22% on combination therapy achieved at least a partial response, whereas no patient with high AAG levels did so.
In vitro work has shown that increasing levels of AAG result in increased half maximal inhibitory concentration (IC50) of ARRY-520, suggesting that patients with elevated AAG may have subtherapeutic exposure to the drug, Dr. Shah explained. AAG does not bind to other standard multiple myeloma agents on the market, and is not correlated with prognostic markers in myeloma.
Nonhematologic adverse events were very low, including one case each of grade 4 fatigue and hypokalemia, and two cases of grade 4 pneumonia.
As expected from the biology of the drug, grade 3/4 hematologic events were more common, but generally reversible and not observed to be cumulative out to 3 years of therapy, Dr. Shah said. Grade 4 neutropenia, thrombocytopenia, and anemia were present in 28%, 25%, and 6% of patients in cohort one and in 38%, 19% and 5% of cohort two, respectively. Febrile neutropenia was grade 3 only, and reported in just one patient in each group, he noted.
Dr. Shah and coauthors reported relationships with study sponsor Array BioPharma, which is developing ARRY-520. Dr. Palumbo disclosed relationships with other companies.