The food and drug administration (FDA) has approved the use of Selinexor, an oral, first-in class, exportin 1 (XPO1) inhibitor, in combination with low-dose dexamethasone in patients with triple-refractory (disease refractory to proteasome inhibitors (PI), immunomodulatory imid agents (IMiD), and anti-Cluster of Differentiation 38 (CD38) monoclonal antibodies (mAb)), or relapsed refractory multiple myeloma (RRMM). SLAMF7 (human Signaling Lymphocyte Activation Molecule Family 7) is a receptor that is present on immune cells, NK (Natural Killer) cells, and plasma cells. Elotuzumab, a mAb directed against the extracellular domain of SLAMF7, is used in combination with an IMiD and dexamethasone to treat RRMM. In this clinical trial, the investigators are proposing the addition of Elotuzumab to Selinexor and low-dose dexamethasone (ESd) in RRMM, previously treated with one or a combination of PI's, IMiD's, and anti-CD38 mAb.
Selinexor reversibly inhibits nuclear export of tumor suppressor proteins (TSPs) resulting in a pro-apoptotic effect. In addition, previous studies found that selinexor alone or in combination with anti-PD-L1 (Programmed Death-Ligand 1) antibody significantly increased the frequency of natural killer cells on immunophenotypic analysis of splenocytes by flow cytometry. Elotuzumab activates NK cells through SLAMF7 and results in NK cell-mediated antibody dependent cellular toxicity (ADCC.) This clinical trial is designed on the premise that these two medications could have a synergistic effect resulting in a better clinical response in the treatment of RRMM. The investigators will evaluate the ORR (overall response rate), CR (Complete Response), VGPR (Very Good Partial Response), PR (Partial Response) rates and the duration of response. Special consideration will be given to multiple myeloma patients with t(11;14) (q13;q32), given it is the most common chromosome translocation in multiple myeloma with early reported activity of Selinexor on BCR (Breakpoint Cluster Region Protein) inhibition. Finally, the investigators will evaluate the correlation between NK function and the response rate to possibly develop a predictive model of response rate to the combination based on NK activity measurements, pre, during, and post treatment. Quantitative testing includes the number of NK (CD3-, CD56/16+) cells, NK subsets (CD56bright to CD56dim ratio) and qualitative testing includes chromium release assay (using 51Cr) for cytotoxicity testing. In addition, the investigators will follow the response of African American patients to this regimen in an ancillary, ad hoc study given the under representation in the STORM (Selinexor Treatment of Refractory Myeloma) trial.
Study Type
This is a single-arm, interventional, phase II clinical trial, in which the anticipated 18 enrolled patients will receive the trial drug, a combination of Elotuzumab, Selinexor, and Dexamethasone in monthly cycles. The study tests the theory of synergy between these drugs, as detailed in the study description above.
Response of relapsed refractory multiple myeloma (RRMM) patient to elotuzumab, selinexor, and dexamethasone (ESd).
Calculate the Overall Response Rate (ORR) as the percentage of participants responding, as per the international working myeloma group (IMWG) criteria, mainly by following bone marrow plasma cell, serum, and urine monoclonal protein and free light chain production, by the date of study completion and on further, predetermined, follow up intervals of the study participants.
Time frame: 18-24 months.
Incidence of adverse events in RRMM patients treated with ESd.
Will be assessed per the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 which is a standardized scale used to quantify the severity of chemotherapy-related adverse events, ranging from grade I, which is the mildest, to grade 4, which is the most severe, and grade 5, which is death.
Time frame: 18-24 months.
Duration of Response (DOR) of RRMM patients to ESd.
DOR is determined by the length of time in months from when measurement criteria for response were first met until the date of first recurrence, progressive disease \[PD\] or death. The unit of measure is month.
Time frame: 18-24 months.
Overall Survival (OS) of RRMM patients treated with ESd.
The investigators will determine the OS to ESd in patients with MM refractory to at least one prior line of treatment. The unit of measure is month.
Time frame: 18-24 months.
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INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE