Patients with smoldering multiple myeloma (SMM), an asymptomatic form of myeloma, do not benefit from treatment with the anti-ICAM1 antibody BI-505, according to the results of a Phase 2 trial.
But the drug is safe, with minimal long-term side effects, and researchers say it warrants further testing in other clinical indications.
The study, “A single-arm, open-label, phase 2 clinical trial evaluating disease response following treatment with BI-505, a human anti-intercellular adhesion molecule-1 monoclonal antibody, in patients with smoldering multiple myeloma,” was published in PLOS One.
Smoldering multiple myeloma is an indolent disease stage, considered to represent the transition from pre-malignant monoclonal gammopathy of undertermined significance (MGUS) to symptomatic multiple myeloma.
Even though this diagnosis provides an opportunity for early intervention, the standard of care for SMM is close observation without treatment until disease progression.
Researchers hypothesized that treating patients with BI-505, an inhibitor of the adhesion molecule ICAM1, could be an effective treatment strategy for SMM patients.
ICAM1 is a cell surface receptor often found in blood cells that is thought to be involved in the development of myeloma and in drug resistance. A Phase 1 trial of BI-505 in patients with relapsed or refractory multiple myeloma showed good tolerability, with 24 percent of patients achieving stable disease for more than eight weeks.
This single-arm, open-label, Phase 2 trial (NCT01838369) was designed to assess the safety and effectiveness of BI-505 in patients with SMM. The trial enrolled four patients, three of whom received the first cycle of treatment, defined as five doses of BI-505 over a seven-week period.
Although all three patients experienced infusion-related adverse events, the researchers say it was not classified as worse than mild or moderate, and describe the treatment as having a benign safety profile.
However, BI-505 showed no clinically relevant effectiveness in any of the patients, suggesting that inhibiting ICAM1 does not benefit patients with smoldering multiple myeloma, and that other approaches should be tested to prevent these patients from progressing to symptomatic myeloma.
“Coming clinical trials will focus on exploring BI-505 activity in settings of lower tumor burden. A clinical Phase 2 study exploring the addition of BI-505 to high dose melphalan and autologous stem cell transplantation has started recruiting patients,” (NCT02756728) the researchers wrote.