APO866 Fails to Be Effective in Cutaneous T-cell Lymphoma

APO866, an injectable molecule that induces cell death by inhibiting the biosynthesis of NAD⁺ (oxidized nicotinamide adenine dinucleotide), failed to demonstrate efficacy in the treatment of patients with relapsed/refractory cutaneous T-cell lymphoma, according to a research letter published in JAMA Dermatology.¹

Because previous studies have shown in vitro and in in vivo that lymphocytes and hematologic cancer cells are very sensitive to APO866, researchers sought to evaluate the agent in a phase 2 clinical trial.

For the multicenter, open-label, single-arm study, researchers enrolled 14 patients with relapsed/refractory cutaneous T-cell lymphoma. Patients were to receive APO866 at a dose of 0.126 mg/m²/hour over 96 hours via continuous IV infusion every 28 days for 3 cycles; however, only 5 patients completed the 3 cycles.

Results showed that at week 16, 1 of 12 evaluable patients achieved a partial response, 6 had stable disease, and 5 had progressive disease. No patient achieved a complete response.

In regard to safety, a total of 18 serious adverse events were reported, of which 7 were related to APO866. These included pyrexia, lymphopenia, spondylitis, staphylococcal sepsis, rhabdomyolysis, and thrombocytopenia. Eighty-six percent of the 14 patients experienced mild to moderate adverse events.

Ultimately, although APO866 demonstrated a reasonable safety profile in cutaneous T-cell lymphoma, it was not powerful enough in this treatment setting. Therefore, researchers see no role for APO866 in cutaneous T-cell lymphoma but potentially for other conditions.

Reference

1. Goldinger SM, Bischof SG, Fink-Puches R, et al. Efficacy and safety of APO866 in patients with refractory or relapsed cutaneous T-cell lymphoma: a phase 2 clinical trial [published online ahead of print March 23, 2016]. JAMA Dermatol. doi: 10.1001/jamadermatol.2016.0401.