Cytokine and Chemokine Profile in Patients with Multiple Myeloma Treated with Bortezomib

Abstract

The aim of the study was to determine the levels of selected cytokines and chemokines in the serum of multiple myeloma (MM) patients treated with bortezomib-based regimens. A total of 71 MM patients were examined: 41 with primary refractory disease (17) or early relapse (28), and 30 who were bortezomib sensitive with no progression for at least six months. Patients who demonstrated CR or PR after bortezomib-based therapies longer than six months after treatment discontinuation were designated bortezomib sensitive. Serum cytokine levels were assayed with Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assay on the MAGPIX Multiplex Reader and the Bio-Plex® 200 System (Bio-Rad). Higher levels of MIP-1α and lower levels of MIP-1β and IL-9 were associated with better responses to bortezomib-based treatment, and higher levels of IL-1ra and IL-8 were associated with bone involvement. MCP-1 was elevated in patients with hemoglobin<10 g/dl compared to those without anemia. The levels of IL-8, MIP-1α, and TNF-α were significantly higher in patients with renal insufficiency. Only MIP-1α was elevated in patients with hypercalcemia compared to patients with normal calcium levels. In conclusion, distinct cytokines are involved in the pathogenesis of MM and may play a prominent role in the prediction of treatment response. However, a single measurement of serum cytokines should be interpreted with caution and further studies are needed.

The Prognostic Value of Whole-Blood PSMB5, CXCR4, POMP and RPL5 mRNA Expression in Patients with Multiple Myeloma Treated with Bortezomib

“…No patients had received bortezomib-based therapy prior to the study. The participants were classified as either bortezomib-sensitive or bortezomib-refractory, as previously reported, according to their response to bortezomib-based therapy [12,53]. Response to treatment and relapse/progression events were classified according to the International Myeloma Working Group (IMWG) [54,55].…”

The Prognostic Value of Whole-Blood PSMB5, CXCR4, POMP, and RPL5 mRNA Expression in Patients with Multiple Myeloma Treated with Bortezomib

“…All of the patients received bortezomib treatment as first-line treatment or in progression after previous therapy. The participants were classified as either bortezomib-sensitive or bortezomib-refractory, as previously reported, according to their response to bortezomib-based therapy [ 12 , 54 ]. Response to treatment and relapse/progression events were classified according to the IMWG [ 55 , 56 ].…”

The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients

“…No patients had received bortezomib-based therapy prior to the study. The participants were classified according to their response to bortezomib-based therapy as either bortezomib sensitive or bortezomib refractory [ 5 ].…”

“…Multiple myeloma often results in bone lesions, hypercalcemia, infections, anemia and production of monoclonal immunoglobulin. The interaction of MM cells with host factors, and the BM microenvironment plays a key role in the molecular evolution of the disease and the generation of treatment-resistant cells; it also influences disease progression with the development of relapsed or refractory disease [ 4 , 5 ]. The treatment of MM has changed in recent years, with the introduction of new drugs, most notably, proteasome inhibitors such as bortezomib, carfilzomib and ixazomib, immunomodulatory drugs (lenalidomide, pomalidomide), a histone deacetylase inhibitors (panobinostat) and monoclonal antibodies (elotuzumab and daratumumab) [ 6 , 7 ].…”