iwMyeloma 2016 | LCL161 – a new approach to treating multiple myeloma

Marta Chesi, PhD, from the Mayo Clinic, Scottsdale, AZ discusses LCL-1 for the treatment of multiple myeloma (MM). LCL161 has an affinity to the cellular inhibitors of apoptosis, cIAP1 and cIAP2. cIAP1 is frequently deleted in myeloma patients and as Dr Chesi explains, when she first treated transgenic mice with LCL161, she expected that it would promote the growth of myeloma as it activates NF-kappa B. However, she observed the opposite, i.e. the tumor burden was reduced in the mice. She further explains that NF-kappa B was activated in the tumor cells as well as the host, which gave the immune cells a boost and allowed them to kill the tumor cells. According to Dr Chesi, this is an interesting approach to treating myeloma as the immune system may be able to out-compete the tumor cells if it is given a boost. A clinical trial of LCL161 in combination with cyclophosphamide (NCT01955434) showed good results and durable disease stabilization in high-risk patients. The challenge is to achieve an even better response rate according to Dr Chesi. The next step will be to combine LCL161 with check-point inhibitors as this combination has already be shown to be successful in mice.
Recorded at the Myeloma 2016 meeting held in Boston, MA.