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      A Case Report of a 58-Year-Old Woman with a Diagnosis of High-Risk Myeloma Refractory to Multiple Line of Therapy and Treated with Selinexor, Bortezomib, and Dexamethasone Prior to Allogeneic Stem Cell Transplantation

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          Abstract

          Patient: Female, 40-year-old

          Final Diagnosis: Multiple myeloma

          Symptoms: Anaemia

          Medication:—

          Clinical Procedure: —

          Specialty: Hematology • Oncology • Transplantology

          Objective:

          Unusual clinical course

          Background:

          Approximately 10% to 15% of patients with multiple myeloma (MM) are diagnosed with high-risk disease and have poor prognosis. Clinical trial data supports the combined use of selinexor, bortezomib, and dexamethasone (XVd) for treatment of patients with MM who have received at least 1 prior therapy. Information on the efficacy of XVd and of subsequent allogeneic stem cell transplantation (SCT) in heavily pretreated patients with high-risk MM is limited.

          Case Report:

          We present a case of a 58-year-old woman with high-risk MM (revised International Staging System Stage III; serum β 2-microglobulin; 8.0 mg/L; and presence of del[17p]) who had received 8 prior treatment lines, and whose disease was refractory to ixazomib, bortezomib, and all immunomodulatory agents. Before initiating XVd (once weekly 1.3 mg/m 2 bortezomib subcutaneously, 80 mg selinexor per os, and 40 mg dexamethasone per os), the patient had severely hypoplastic bone marrow and was transfusion dependent. After 1 cycle of XVd, she achieved a partial response, and after 4 cycles, a very good partial response (VGPR). No adverse reactions to selinexor were observed. Because of the VGPR, a haploidentical transplant was planned. At posttransplant week 4, the patient had become transfusion independent. She remained relapse-free for 13 months after initiating XVd. Maintenance treatment with lenalidomide was initiated, and following receipt of donor lymphocyte infusions due to loss of donor chimerism, the patient’s light chain levels improved.

          Conclusions:

          This report presents the cytogenetics and management of a heavily pretreated patient with high-risk MM treated with SVd followed by SCT.

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          Most cited references21

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          Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group.

          The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM).
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            Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT.

            We previously reported that the Charlson Comorbidity Index (CCI) was useful for predicting outcomes in patients undergoing allogeneic hematopoietic cell transplantation (HCT). However, the sample size of patients with scores of 1 or more, captured by the CCI, did not exceed 35%. Further, some comorbidities were rarely found among patients who underwent HCT. Therefore, the current study was designed to (1) better define previously identified comorbidities using pretransplant laboratory data, (2) investigate additional HCT-related comorbidities, and (3) establish comorbidity scores that were suited for HCT. Data were collected from 1055 patients, and then randomly divided into training and validation sets. Weights were assigned to individual comorbidities according to their prognostic significance in Cox proportional hazard models. The new index was then validated. The new index proved to be more sensitive than the CCI since it captured 62% of patients with scores more than 0 compared with 12%, respectively. Further, the new index showed better survival prediction than the CCI (likelihood ratio of 23.7 versus 7.1 and c statistics of 0.661 versus 0.561, respectively, P < .001). In conclusion, the new simple index provided valid and reliable scoring of pretransplant comorbidities that predicted nonrelapse mortality and survival. This index will be useful for clinical trials and patient counseling before HCT.
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              • Abstract: found
              • Article: not found

              Oral Selinexor–Dexamethasone for Triple-Class Refractory Multiple Myeloma

              Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options.
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                Author and article information

                Journal
                Am J Case Rep
                Am J Case Rep
                amjcaserep
                The American Journal of Case Reports
                International Scientific Literature, Inc.
                1941-5923
                2022
                21 April 2022
                : 23
                : e935353-1-e935353-5
                Affiliations
                [1 ]Department of Hematology, Alberts Cellular Therapy, Dr Brittain & Partners Incorporated, Netcare Pretoria East Hospital, Pretoria, South Africa
                [2 ]Scientific and Medical Publications, Karyopharm Therapeutics Inc., Newton, MA, USA
                [3 ]Department of Research, Karyopharm Therapeutics Inc., Newton, MA, USA
                Author notes
                Corresponding Author: Michael Cass, e-mail: michael.cass@ 123456haemalife.co.za

                Authors’ Contribution:

                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Financial support: Writing of this work was supported by Karyopharm Therapeutics Inc.

                Conflict of interest: Osnat Ben-Shahar, Yosef Landesman, and Trinayan Kashyap are employees of Karyopharm Therapeutics Inc.

                Article
                935353
                10.12659/AJCR.935353
                9040079
                35444159
                7732e226-e5e4-4010-800d-5c84ffe41f2f
                © Am J Case Rep, 2022

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

                History
                : 03 November 2021
                : 31 December 2021
                : 18 March 2022
                Categories
                Articles

                cytogenetics,hematopoietic stem cell transplantation,multiple myeloma,selinexor

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