Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster II
A phase 2 clinical trial of LCL161 was conducted in 24 patients with relapsed MM previously exposed to both IMiDs and PIs, but less than 5 prior lines of therapy. Patients received LCL161 1200mg po weekly, with Cy 500mg po weekly added for progressive disease or lack of response. Single agent LCL161 was well-tolerated, with grade 3 or 4 non-hematologic toxicity in four patients, and following the addition of cyclophosphamide in 9 patients. No patients responded to single agent LCL161, and the best response was stable disease in 6/24. In 21 patients, Cy was added after a median of 2 cycles, in whom the best response was stable disease or better in 18/21 (p<0.001 compared to LCL161 alone), and a PR or better (including 1 VGPR and 1 CR) in 5/21 (p<0.001 compared to LCL161 alone). Six months following the initiation of Cy, 35% of patients remain event-free. Two patients had stable disease for more than nine months after stopping treatment. One, relapsing after VDT-PACE, HDM200, RVd x 3 years with t(11;14) and del17p, received only three months of LCL161, the last month in combination with Cy. He then achieved a PR, reconstitution of his uninvolved IgG to normal levels for the first time in more than 3 years and still has not progressed one year after stopping therapy. Similar changes in serum and bone marrow inflammatory cytokines and gene expression were observed in patients following treatment with LCL161 to those observed in the mice. We conclude that LCL161 is able to modulate the tumor microenvironment to exert long-term disease control in combination with Cy, and deserves further study in combination with agents that more directly depend on phagocytic cell activity (e.g., monoclonal antibodies, inhibitors of “Don’t eat me” signals).
Disclosures: Bergsagel: Novartis: Research Funding ; Constellation Pharmaceuticals: Research Funding ; Incyte: Consultancy ; Jannsen: Consultancy ; Mundipharma: Consultancy . Off Label Use: Use of LCL161 to treat multiple myeloma. Kumar: Celgene: Research Funding ; Millenium/Takeda: Research Funding ; Onyx: Research Funding ; AbbVie: Research Funding ; Janssen: Research Funding ; Sanofi: Research Funding ; Celgene, Millenium, Sanofi, Skyline, BMS, Onyx, Noxxon,: Other: Consultant, no compensation, ; Skyline, Noxxon: Honoraria . Stewart: Oncospire Genomics: Research Funding .
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