Photo by Linda Bartlett
The monoclonal IgM antibody PAT-SM6 was “well-tolerated” and showed “modest clinical activity” in patients with relapsed or refractory multiple myeloma (MM), researchers reported in haematologica.
Adverse events occurred in all 12 patients enrolled in the phase 1/2a study, but most were considered unrelated to treatment.
A third of patients, all of whom had progressive disease upon study entry, achieved stable disease after receiving PAT-SM6. The remaining patients progressed.
Leo Rasche, MD, of University Hospital Wurzburg in Germany, and his colleagues conducted this study. It was funded, in part, by Patrys Limited, the company developing PAT-SM6.
The study included 12 heavily pretreated MM patients. They had a median age of 69.5 years and a long-standing history of MM (range, 3.25 to 15.75 years). They had received a median of 3.9 prior lines of therapy (range, 2-7).
Patients received 4 escalating doses of PAT-SM6, over a period of 2 weeks, via intravenous infusions at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 6 mg/kg.
Safety data
There were 54 treatment-emergent adverse events in all 12 patients. However, there were no dose-limiting toxicities and no deaths. The maximum tolerated dose has not been reached.
More than 80% of the adverse events were of mild to moderate intensity. Two patients (16.6%) each experienced a single serious event. One patient had acute back pain, and one had a bile duct stone. Neither of these events was considered treatment-related.
Twenty-one adverse events were considered treatment-related. This included leukopenia (66.6%), neutropenia (50%), hypertension (16.6%), catheter-related thrombophlebitis (8.3%), injection site erythema (8.3%), slight headache (8.3%), C-reactive protein increase (8.3%), and hypertriglyceridemia (8.3%).
Efficacy data
Most patients progressed following treatment, but 4 (33.3%) had stable disease. The investigators noted that stable disease is not necessarily connected with a clinical benefit, so they analyzed the 4 patients in detail.
Patient 4, who received PAT-SM6 at 1 mg/kg, entered the study with high-risk disease. The patient had 13q deletion and 1q21 gain, had received 5 prior lines of therapy, and was refractory to novel agents, including pomalidomide and bortezomib.
The patient was treatment-free for 1 month prior to receiving PAT-SM6. During treatment, there were no symptoms of active myeloma, and the patient asked to continue salvage therapy 1 week after the end of the study.
Patient 7, who received PAT-SM6 at 3 mg/kg, had been diagnosed with MM for 15 years and had received 4 prior lines of therapy.
The patient’s treatment-free interval before receiving PAT-SM6 was 30 months. After PAT-SM6, the patient was therapy-free for 4.6 months.
Patient 10, who received PAT-SM6 at 6mg/kg, had 6 prior lines of therapy, including tandem autologous stem cell transplant and several polychemotherapeutic regimens.
The patient was therapy-free for 4 months prior to receiving PAT-SM6. The patient requested salvage therapy 1 month after receiving PAT-SM6.
Patient 11, who received PAT-SM6 at 6mg/kg, had 4 prior lines of therapy and was refractory to both lenalidomide and thalidomide.
The patient’s treatment-free interval prior to PAT-SM6 was 12 months. After PAT-SM6, the patient was therapy-free for 5.2 months.
The researchers said additional trials testing PAT-SM6 in combination with other MM therapies are planned. PAT-SM6 has received orphan drug designation for MM in the US and the European Union.
