Detection of NFKB2 3’end Loos By Quantitative PCR (QPCR) or Detection of NFKB2 Rearrangements Correlate with Bortezomib Response in Multiple Myeloma

Background: Multiple myeloma is a malignant plasma cell cancer that is increasing in frequency in today’s aging population. While proteasome inhibitors such as bortezomib have improved the outcome of treatment, many patients fail to achieve a complete remission and ultimately the disease progresses. With these new treatments come higher associated toxicities and significant healthcare costs for the drugs. Several new cancer therapies with companion diagnostics have been approved in parallel with the drug to guide physicians in selecting those patients who would specifically benefit from the drug. No such test exists for the use of bortezomib in multiple myeloma. We have previously demonstrated that the 3’ end of the nuclear factor kappa-B 2 (NFKB2/p100) gene, a member of the NFKB/Rel gene family, functions as a mediator of bortezomib apoptotic effect through the induction of caspase 8 activation. Methodology: We have investigated the loss of NF-kB2 3’end loss by quantitative PCR (QPCR) in 56 MM patients and by break-apart Fluorescent In-Situ Hybridization in the whole bone marrow of 31 patients as well as in sorted cells of 24 MM patients treated with bortezomib containing regimens. Quality of response was assessed after 4 cycles of treatment initiation. QPCR was measured in peripheral blood lymphocyte and CD138 positive cells from the bone marrow to generate a QPCR ratio. Results: 37 of the 56 newly diagnosed patient with MM achieved >partial response (PR), while 16 remained stable or progress to treatment. The mean QPCR ratio in responders was 1.69 ± 0.13, while in non-responder was 0.43 ± 0.1 (p Conclusion: loss of NF-kB2 3’ end is a potential companion diagnostic test for bortezomib. QPCR is more sensitive to detect NFKB2 3’end abnormalities. Disclosures Kelkar: Empire Genomics: Employment. Kaplan:Empire Genomics: Employment. Lonial:Millennium: The Takeda Oncology Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding.