Is surgical indication in multiple myeloma a poor prognosis sign? SEER database analysis

Aim This study aims to investigate demographic data, survival rates, and the relationship of these rates with surgery in a large case series including multiple myeloma (MM) patients. Method MM cases were analyzed retrospectively using the latest version of the SEER database published in April 2020. This version covers January 1975 to December 2017. Patients were classified according to gender, age, and race/ethnicity. Tumors were classified according to their localization, grade, year of diagnosis, and follow-up results. Results There were 60,239 patients diagnosed with Plasma Cell Myeloma. While 670 patients (1.2%) were operated on, 43,976 patients (76.7%) did not indicate operation, and 12,670 patients (22.1%) could not be operated on despite the recommendation. The mean survival was 62 months in those without an indication for surgery, and 42 months in patients with an indication but could not be operated on, and the difference was significant (p = 0.001). The mean survival was 58 months in the operated patients, and 42 months in the patients who could not be operated on despite the indication, and the difference was significant (p = 0.001). There was no difference between those who did not indicate surgery and those who were operated on with an indication (p = 0.243). Conclusion In multiple myeloma, the best prognosis is in the group of patients who received medical treatments without any indication for operation, while an indication for operation indicates a worse prognosis. A worse prognosis should be expected in patients who do not accept the operation or who cannot be operated on compared to the operated patients (AU)

Is surgical indication in multiple myeloma a poor prognosis sign? SEER database analysis.

AIM: This study aims to investigate demographic data, survival rates, and the relationship of these rates with surgery in a large case series including multiple myeloma (MM) patients. METHOD: MM cases were analyzed retrospectively using the latest version of the SEER database published in April 2020. This version covers January 1975 to December 2017. Patients were classified according to gender, age, and race/ethnicity. Tumors were classified according to their localization, grade, year of diagnosis, and follow-up results. RESULTS: There were 60,239 patients diagnosed with Plasma Cell Myeloma. While 670 patients (1.2%) were operated on, 43,976 patients (76.7%) did not indicate operation, and 12,670 patients (22.1%) could not be operated on despite the recommendation. The mean survival was 62 months in those without an indication for surgery, and 42 months in patients with an indication but could not be operated on, and the difference was significant (p = 0.001). The mean survival was 58 months in the operated patients, and 42 months in the patients who could not be operated on despite the indication, and the difference was significant (p = 0.001). There was no difference between those who did not indicate surgery and those who were operated on with an indication (p = 0.243). CONCLUSION: In multiple myeloma, the best prognosis is in the group of patients who received medical treatments without any indication for operation, while an indication for operation indicates a worse prognosis. A worse prognosis should be expected in patients who do not accept the operation or who cannot be operated on compared to the operated patients.

[Total Gastrectomy for Gastric Invasion of Multiple Myeloma-A Case Report].

A 65-year-old woman was referred to our hospital for lumbago. The patient was diagnosed with multiple myeloma in 2020. She underwent chemotherapy and radiation therapy, and the disease progression stabilized. In 2022, the patient presented with severe anemia(Hb 4.9 mg/dL), and upper gastrointestinal endoscopy revealed a type 1 tumor in the middle body of the stomach. Computed tomography showed masses in the stomach and pancreas. The patient required a large volume of blood transfusion and underwent total gastrectomy to control the bleeding. Histological examination of the resected specimen indicated infiltration of myeloma cells. The patient died from invasive lesions in other organs, a year after surgery. Usually, extramedullary multiple myeloma lesions occur in the liver, spleen, and lymph nodes. Gastric invasion of multiple myeloma is very rare. Because of poor prognosis, surgery for gastric invasion of multiple myeloma is even rarer. We report a case of gastric invasion of multiple myeloma with a literature review.

Analysis of complications and revisions after spine surgery in 270 multiple myeloma patients with spinal involvement.

BACKGROUND CONTEXT: Patients with multiple myeloma (MM) are at increased risk of infections and suffer from poor bone quality due to their disseminated malignant bone disease. Therefore, postoperative complications may occur following surgical treatment of MM lesions. PURPOSE: In this study, we aimed to determine the incidence of postoperative complications and retreatments after spinal surgery in MM patients. Additionally, we sought to identify risk factors associated with complications and retreatments. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: In total, 270 patients with MM who received surgical treatment for spinal involvement between 2008 and 2021 were included. OUTCOME MEASURES: The incidence of perioperative complications within 6 weeks and reoperations within 2.5 years and individual odds ratios for factors associated with these complications and reoperations. METHODS: Data were collected through manual chart review. Hosmer and Lemeshow's purposeful regression method was used to identify risk factors for complications and reoperations. RESULTS: The median age of our cohort was 65 years (SD = 10.8), and 58% were male (n = 57). Intraoperative complications were present in 24 patients (8.9%). The overall 6-week complication rate after surgery was 35% (n = 95). The following variables were independently associated with 6-week complications: higher Genant grading of a present vertebral fracture (OR 1.41; 95% CI 1.04-1.95; p = .031), receiving intramuscular or intravenous steroids within a week prior to surgery (OR 3.97; 95% CI 1.79-9.06; p = .001), decompression surgery without fusion (OR 6.53; 95% CI 1.30-36.86; p = .026), higher creatinine levels (OR 2.18; 95% CI 1.19-5.60; p = .014), and lower calcium levels (OR 0.58; 95% CI 0.37-0.88; p = .013). A secondary surgery was indicated for 53 patients (20%), of which 13 (4.8%) took place within two weeks after the initial surgery. We additionally discovered factors associated with retreatments, which are elucidated within the manuscript. CONCLUSION: The goal of surgical treatment for MM bone disease is to enhance patient quality of life and reduce symptom burden. However, postoperative complication rates remain relatively high after spine surgery in patients with MM, likely attributable to both inherent characteristics of the disease and patient comorbidities. The risk for complications and secondary surgeries should be explored and a multidisciplinary approach is crucial.

Postoperative Outcomes in Total Hip and Total Knee Arthroplasty for Patients Who Have Multiple Myeloma.

BACKGROUND: Advancements in oncologic care have increased the longevity of patients who have multiple myeloma, although outcomes beyond the early postoperative period following total hip arthroplasty (THA) and total knee arthroplasty (TKA) remain unknown. This study investigated the influence of preoperative factors on implant survivorship following THA and TKA after a minimum 1-year interval for multiple myeloma patients. METHODS: Using our institutional database, we identified 104 patients (78 THAs, 26 TKAs) from 2000 to 2021 diagnosed with multiple myeloma before their index arthroplasty by International Classification of Diseases, Ninth and Tenth Revisions (ICD-9 and ICD-10) codes 203.0× and C90.0× and corresponding Current Procedural Terminology (CPT) codes. Demographic data, oncologic treatments, and operative variables were collected. Multivariate logistic regressions assessed variables of interest, and Kaplan-Meier curves were used to estimate implant survival. RESULTS: There were 9 (11.5%) patients who underwent revision THA after an average time of 1,312 days (range, 14 to 5,763), with infection (33.3%), periprosthetic fracture (22.2%), and instability (22.2%) being the most common indications. Of these patients, 3 (33.3%) underwent multiple revision surgeries. There was 1 (3.8%) patient who underwent revision TKA at 74 days postoperatively for infection. Patients treated with radiotherapy were more likely to require revision THA (odds Rratio (OR): 6.551, 95% confidence interval (CI): 1.148-53.365, P = .045), but no predictors of failure were identified for TKA patients. CONCLUSION: Orthopaedic surgeons should know that multiple myeloma patients have a relatively high risk of revision, particularly following THA. Accordingly, patients who have risk factors for failure should be identified preoperatively to avoid poor outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Risk-benefit ratio of percutaneous kyphoplasty and percutaneous vertebroplasty in patients with newly diagnosed multiple myeloma with vertebral fracture: a single-center retrospective study.

The indications for percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP) are painful vertebral compression fractures. Our study is to assess the risk-benefit ratio of PKP/PVP surgery in the patients with newly diagnosed multiple myeloma (NDMM) without receiving antimyeloma therapy. The clinical data of 426 consecutive patients with NDMM admitted to our center from February 2012 to April 2022 were retrospectively analyzed. The baseline data, postoperative pain relief, the proportion of recurrent vertebral fractures, and survival time were compared between the PKP/PVP surgical group and the nonsurgical group in the NDMM patients. Of the 426 patients with NDMM, 206 patients had vertebral fractures (206/426, 48.4%). Of these, 32 (32/206, 15.5%) underwent PKP/PVP surgery for misdiagnosis of simple osteoporosis prior to diagnosis of MM (surgical group), and the other 174 (174/206, 84.5%) did not undergo surgical treatment prior to definitive diagnosis of MM (non-surgical group). The median age of patients in the surgical and nonsurgical groups was 66 and 62 years, respectively (p = 0.01). The proportion of patients with advanced ISS and RISS stages was higher in the surgical group (ISS stage II + III 96.9% vs. 71.8%, p = 0.03; RISS stage III 96.9% vs. 71%, p = 0.01). Postoperatively, 10 patients (31.3%) never experienced pain relief and 20 patients (62.5%) experienced short-term pain relief with a median duration of relief of 2.6 months (0.2-24.1 months). Postoperative fractures of vertebrae other than the surgical site occurred in 24 patients (75%) in the surgical group, with a median time of 4.4 months postoperatively (0.4-86.8 months). Vertebral fractures other than the fracture site at the first visit occurred in 5 patients (2.9%) in the nonoperative group at the time of diagnosis of MM, with a median time of 11.9 months after the first visit (3.5-12.6 months). The incidence of secondary fractures was significantly higher in the surgical group than in the nonsurgical group (75% vs. 2.9%, p = 0.001). The time interval between the first visit and definitive diagnosis of MM was longer in the surgical group than in the nonsurgical group (6.1 months vs. 1.6 months, p = 0.01). At a median follow-up of 32 months (0.3-123 months), median overall survival (OS) was significantly shorter in the surgical group than in the nonsurgical group (48.2 months vs. 66 months, p = 0.04). Application of PKP/PVP surgery for pain relief in NDMM patients without antimyeloma therapy has a limited effect and a high risk of new vertebral fractures after surgery. Therefore, patients with NDMM may need to have their disease controlled with antimyeloma therapy prior to any consideration for PKP/PVP surgery.

Non-Cryopreserved Peripheral Blood Stem Cell Graft for Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma and Lymphoma Patients.

BACKGROUND Hematopoietic stem cell transplantation (HSCT) using cryopreserved grafts is time-consuming, expensive treatment, and may associated with dimethyl sulfoxide (DMSO) toxicity. Here, we assess the clinical utility and safety of non-cryopreserved peripheral blood stem cell graft in autologous HSCT. MATERIAL AND METHODS Medical data of multiple myeloma or lymphoma patients who underwent autologous non-cryopreserved HSCT were reviewed. RESULTS A total of 58 patients (40 myeloma and 18 lymphoma) were reviewed. The median myeloma and lymphoma CD34⁺ cell doses were 7.59 and 6.9 million/kg, respectively, with good viability after storage. The median times in neutrophil and platelet engraftment were 9 and 13 days and 11 and 14 days in myeloma and lymphoma, respectively. Only 5 patients in this cohort developed serious post-transplant complications. After transplantation, the cumulative incidence of relapse at 5 years was 34.4% in myeloma versus 19.1% in lymphoma patients. Notably, the mortality incidence rate rapidly increased within the first year and reached a plateau after 4 years, with cumulative incidence of 5.9% and 30.9% in myeloma and lymphoma, respectively. With a median follow-up time of 60 months, the median progression-free survival (PFS) and overall survival (OS) for lymphoma patients was 123.8 and 130 months, respectively. For the myeloma group, the median follow-up time was 38.6 months, the median PFS was 99.5 months, and OS was 157 months. CONCLUSIONS Non-cryopreserved HSCT is effective and safe. The long-term survival outcomes could be achieved by the shortening the duration of neutrophil and platelet engraftments and the complication rates are acceptable.

Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma.

BACKGROUND: In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown. METHODS: In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point was progression-free survival. RESULTS: Among 357 patients in the RVD-alone group and 365 in the transplantation group, at a median follow-up of 76.0 months, 328 events of disease progression or death occurred; the risk was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% confidence interval [CI], 1.23 to 1.91; P<0.001); median progression-free survival was 46.2 months and 67.5 months. The percentage of patients with a partial response or better was 95.0% in the RVD-alone group and 97.5% in the transplantation group (P = 0.55); 42.0% and 46.8%, respectively, had a complete response or better (P = 0.99). Treatment-related adverse events of grade 3 or higher occurred in 78.2% and 94.2%, respectively; 5-year survival was 79.2% and 80.7% (hazard ratio for death, 1.10; 95% CI, 0.73 to 1.65). CONCLUSIONS: Among adults with multiple myeloma, RVD plus ASCT was associated with longer progression-free survival than RVD alone. No overall survival benefit was observed. (Funded by the National Heart, Lung, and Blood Institute and others; DETERMINATION ClinicalTrials.gov number, NCT01208662.).

Highly proliferative and functional PD-1+ and TIM-3+ T cells are transiently increased in multiple myeloma following autologous hematopoietic stem cell transplantation.

The aim of our prospective study was to assess recovery dynamics and functional characteristics of PD-1+ and TIM-3+ T cells in multiple myeloma (MM) patients following high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (AHSCT). Peripheral blood, autograft and bone marrow samples were obtained from 46 MM patients before conditioning, at the engraftment, following six and 12 months post-transplant. Frequencies of CD4+ and CD8+ T cells expressing PD-1 and TIM-3 and intracellular expression of Ki-67 and Granzyme B were evaluated. Counts of PD-1+ and TIM-3+ T cells at the engraftment were significantly higher comparing with the levels before HDCT and 6-12 months following AHSCT. The post-transplant increase in the studied subsets was due to a temporary enhancement in proliferation activity. The cytotoxic potential of PD-1- and TIM-3-expressing CD8+ T cells was higher at the engraftment comparing with the pre-transplant and remained at the same level for at least 12 months. The increase in CD4+PD-1+ and CD8+TIM-3+ T cells at the engraftment was associated with higher absolute counts of their reinfused counterparts. Circulating PD-1+ CD8+ and TIM-3+ CD4+ T cells were increased in patients after post-transplant relapse comparing with the ones in remission. Homeostatic proliferation plays a key role in the upregulation of inhibitory checkpoint receptors on functional T cells under lymphopenic conditions. In this regard, it is difficult to predict both the efficacy and adverse reactions of therapy with checkpoint inhibitors on the course of MM after HDCT with AHSCT. Précis. Homeostatic proliferation plays apparently a key role in the upregulation of PD-1 and TIM-3 on functional T cells after AHSCT and appears to be a normal physiological process, contrary to relapse-associated increase in PD-1+ and TIM-3+ T cells.

Role of vertebroplasty and balloon kyphoplasty in pathological fracture in myeloma: a narrative review.

BACKGROUND: Up to 70% of multiple myeloma (MM) patients develop vertebral metastasis and subsequent pathological vertebral fractures (PVF). With contemporary systemic therapies, life expectancy of MM patients has improved drastically, and the need to manage pain and associated disability from PVF is increasingly a high priority. The aim of this review is to provide an updated comprehensive synthesis of evidence in the use of vertebral augmentation, including percutaneous vertebroplasty (PV) and balloon kyphoplasty (BKP), to treat MM-related PVF. METHODS: A comprehensive multi-database search in accordance with PRISMA guidelines was performed up to 10 February 2021. Relevant English language articles were selected and critically reviewed. FINDINGS: A total of 23 clinical studies have been included in the review. PV and BKP showed significant pain and functional improvements in terms of analgesia requirements, Cervical Spine Function Score, Eastern Cooperative Oncology Group scale, EQ-5D score, Karnofsky score, Neck Pain Disability Index, Oswestry Disability Index, Short form-36 (SF-36) questionnaire and VAS pain scale. Both procedures also reported promising radiographic outcomes in terms of vertebral height improvement, maintenance and restoration, as well as kyphotic deformity correction. Asymptomatic cement leakage was commonly reported. There was no significant difference between the two procedures. CONCLUSION: PV and BKP are safe and effective procedure that offers pain relief, reduction in pain associated disability and reduction of fracture incidence. Its minimally invasive approach is associated with minimal morbidity risk, making it a viable option in frail patients. LEVEL OF EVIDENCE IV: Narrative review.

Multiple myeloma complicated by skull plasmacytoma discovered after head injury.

Plasmacytoma is a malignant tumor originating from the plasma cells of the bone marrow. Those discovered after a head injury is rare. We report a case of a 48-year-old female who complained of scalp mass without other symptoms after head injury. Meningioma was considered preoperatively based on imaging findings, and surgical resection was performed. Postoperatively, multiple myeloma complicated by skull plasmacytoma was diagnosed by histopathology and systematic examinations in succession. When evaluating a head mass that appeared after a head injury, plasmacytoma should be considered at times. Osteolytic changes and biconvex form on imaging are beneficial to differentiation.

Disparities in Utilization of Autologous Stem Cell Transplantation as Consolidative Therapy for Multiple Myeloma: A Single Institution Retrospective Review.

BACKGROUND: Most guidelines recommend induction therapy followed by autologous hematopoietic cell transplantation. A Surveillance, Epidemiology, and End Results-Medicare database analysis from 2000 to 2011 noted a lower use of HCT and bortezomib among Black patients, despite adjusting for care barriers, and this practice was associated with a poorer outcome. The goal of this study was to evaluate patterns of acceptance of HCT as consolidative therapy for MM. METHODS: Cox proportional hazards model was used to investigate the association between the survival time of the patients (overall survival) and age of the diagnosis, race, socioeconomic status, disease cytogenetic, and initial induction regimens. A total of 194 patients with a confirmed diagnosis of MM who were referred for HCT between January 1, 2009, and June 30, 2019, were included in this study. Patients who received autologous stem cell transplant for relapsed MM were excluded. RESULTS: We found that income category was not significantly associated with overall survival, time to transplant or transplant-/relapse-related mortality. High-risk cytogenetic was significantly associated with shorter overall survival, higher transplant-related mortality and relapse-related mortality (P < .002). The use of aggressive induction choices was associated with poorer transplant outcomes (P = .02). Time to transplant tended to be shorter in African American compared with other ethnic groups (P = .07). CONCLUSION: There was no significant difference in the use rate of the HCT between Caucasians and AA patients with MM. Further comparative studies of MM induction therapy and access to clinical trials in African Americans and other racial minorities are warranted.

Surgical Stabilization for Patients with Mechanical Back Pain Secondary to Metastatic Spinal Disease is Associated with Improved Objective Mobility Metrics: Preliminary Analysis in a Cohort of 26 Patients.

OBJECTIVES: To investigate the effect of surgical stabilization for patients with metastatic spinal disease on objective mobility metrics. METHODS: A retrospective chart review identified patients who had mechanical back pain from metastatic spinal disease and underwent spinal stabilization during 2017. Mobility metrics, the Activity Measure for Post-Acute Care (AM-PAC) inpatient mobility short form (IMSF) and the Johns Hopkins Highest Level of Mobility (JH-HLM), were reviewed. RESULTS: A total of 26 patients were included in the analysis with median hospital stay of 8 days. Preoperative JH-HLM scores were available for 17 patients with a mean score of 5.4, increasing to mean score of 6.6 at last follow-up (P = 0.036). Preoperative AM-PAC IMSF scores were available for 14 patients with a mean score of 19.4, decreasing slightly to a mean score of 18.7 at last follow-up (P = 0.367). Last follow-up with mobility metrics occurred a median of 6.5 days postoperatively (range: 3-66 days). Multivariable analysis showed that American Spinal Injury Association and Karnofsky Performance Status scores were significantly associated with both JH-HLM and AM-PAC mobility scores at last follow-up. A higher JH-HLM or AM-PAC score was significantly associated with direct home discharge and a higher AM-PAC score was associated with shorter hospital stay. CONCLUSIONS: Surgical stabilization for patients with mechanical back pain secondary to metastatic spinal disease might lead to an objective improvement in JH-HLM score. JH-HLM and AM-PAC scores may be correlated with length of hospital stay and discharge disposition. Future studies are encouraged to further characterize the role of these mobility metrics in the management plan of these patients.

Huge Sellar Plasmacytoma as Differential Diagnosis of Invasive Pituitary Adenoma: A Case Report

Sellar plasmacytomas are rare tumors arising from plasma cells. They are often misdiagnosed as adenomas.We report the case of a 63-year-old woman with headache, cranial nerve III palsy and decreased visual acuity. Imaging revealed an extensive lesion centered on the clivus, extending to the cavernous sinus bilaterally and into the sphenoid sinus. The hormonal tests were compatible with panhypopituitarism and mild hyperprolactinemia. The first hypothesis was invasive pituitary adenoma. Partial resection was achieved, and the immunohistochemical evaluation was compatible with plasmacytoma. After a few weeks, she developed lumbar and hip pain, and the imaging confirming osteolytic lesions. The final diagnosis was multiple myeloma.

KD-PACE Salvage Therapy for Aggressive Relapsed Refractory Multiple Myeloma, Plasma Cell Leukemia and Extramedullary Myeloma.

BACKGROUND: Patients with advanced/aggressive multiple myeloma have limited treatment options to achieve rapid disease control. In eligible patients, bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide is often used. However, many patients are refractory to or have toxicities from bortezomib and there is a need for bridging therapy. We have used a modified regimen incorporating the second-generation proteasome inhibitor carfilzomib (carfilzomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide and etoposide [KD-PACE]) instead of bortezomib for relapsed/refractory multiple myeloma. PATIENTS AND METHODS: This 2-center retrospective study included consecutive patients receiving KD-PACE for relapsed or refractory multiple myeloma, plasma cell leukemia, or extramedullary myeloma. The primary outcome was the feasibility of KD-PACE as a bridging therapy to a more definitive treatment option. RESULTS: Fifty-two patients were included. The median age was 57 years, and 67% were male. Thirty-one patients were bridged with KD-PACE to autologous hematopoietic stem cell transplant (29%), allogenic hematopoietic stem cell transplant (27%), or a clinical trial (12%). Patients bridged to autologous hematopoietic stem cell transplant, allogenic hematopoietic stem cell transplant, or a clinical trial had a superior progression-free survival (8.3 months vs 2.3 months in the nonbridged group; P < .001) and overall survival (median, 16.7 months vs 4.3 months in the nonbridged group; P < .001). No unexpected toxicities occurred from the treatment regimen. CONCLUSION: KD-PACE is a promising treatment option for select patients with advanced/aggressive forms of myeloma requiring rapid disease control before a more definitive salvage therapy such as auto/allotransplantation or a clinical trial.

Clinical outcomes and complications of surgical interventions for multiple myeloma lesions in the extremities and pelvis: A retrospective clinical study.

OBJECTIVE: This study aimed to assess the pain and functional status of patients who underwent various surgical interventions for the stabilization of selected multiple myeloma (MM) lesions in the extremities and pelvis and to investigate the rate of complications requiring reintervention. METHODS: Patients with MM who underwent various surgical interventions for the extremity or pelvic lesions were retrospectively reviewed. Change in the pain intensity was assessed using visual analogous scale (VAS) preoperatively, at the time of discharge, and at the final follow-up. Functional status was assessed using the musculoskeletal tumor society (MSTS) scoring system for both upper and lower extremities preoperatively and at the final follow-up. Postoperative complications requiring reintervention, including dislocation, loss of fixation/aseptic loosening of prosthesis, mechanical insufficiency, periprosthetic fracture, infection, or progression of the local disease, were recorded. RESULTS: A total of 49 (20 men and 29 women) previously (23) or newly (26) diagnosed patients with a mean age of 60.8±18.2 years were included in this study. Of these, 6 patients underwent multiple surgeries for different skeletal sites; in total, 57 procedures were performed. The mean follow-up was 47.7±21.63 months. The lesions were localized to the humerus (19), radius (1), pelvis (4), femur (30), and tibia (3). The surgical indications included therapy-refractory pain for 17 patients and pathological fractures due to progression of pre-existing lesions for 12 patients or newly diagnosed lesions with extensive bone destruction at initial presentation for 28 patients. Surgical procedures included prosthetic reconstruction in 32 patients, cement-augmented osteosynthesis in 9, and closed intramedullary nailing in 16. The mean VAS score decreased from 8.75±1.2 preoperatively to 3.21±1.56 at the time of discharge and 1.2±0.42 at the final follow-up. Although a significant decrease was detected between the preoperative and postoperative VAS scores at the time of discharge (p=0.0001), the decrease between the time of discharge and the final follow-up was statistically insignificant (p=0.086). The mean MSTS score significantly improved from 9.1%±6.4% (range: 0%-40%) preoperatively to 76%±14.9% (range: 40%-93.3%) at the final follow-up (p=0.0001). Significantly higher MSTS scores were obtained in the upper extremity than lower extremity/pelvis (p=0.04) and in isolated diaphyseal involvement than metaphyseal or articular involvement (p=0.032). A total of 11 complications requiring reintervention (19.2%) were observed, which included dislocation (3.5%), loss of fixation (5.2%), mechanical insufficiency (3.5%), infection (5.2%), and local tumor progression (1.7%). The rate of complications requiring reintervention was lower but statistically insignificant in the upper extremity (5%; 1/20) than lower extremity/pelvis (27%; 10/37) (p=0.076) and in isolated diaphyseal involvement (6.2%; 1/16) than metaphyseal or articular involvement (24.3%; 10/41) (p=0.079). CONCLUSION: Although different types of surgeries can achieve pain relief and good function in different anatomical localizations, better functional results with lower complication rates may be obtained following surgical management of MM lesions in the upper extremities and in diaphyseal localizations. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

JMJD2C triggers the growth of multiple myeloma cells via activation of ß­catenin.

Emerging evidence has indicated that histone modification and its related regulators are involved in the progression of multiple myeloma (MM) cells. In the present study, the expression of Jumonji C domain­containing 2 (JMJD2) was examined in both MM tissues and healthy controls. The roles of JMJD2C in the progression of MM were further investigated. The results revealed that the expression of JMJD2C, but not that of JMJD2A or JMJD2B, was increased in MM tissues compared with the healthy controls. The overexpression of JMJD2C significantly increased the in vitro growth of MM cells. The inhibitor of the ß­catenin signaling pathway significantly attenuated the JMJD2C­induced growth of MM cells. Mechanistical analyses indicated that JMJD2C increased the transcription of ß­catenin in MM cells, which may be due to the fact that JMJD2C can directly bind with the promoter of ß­catenin. Furthermore, JMJD2C activated ß­catenin in MM cells via a GSK3ß­dependent manner, which was evidenced by the results demonstrating that the overexpression of GSK3ß attenuated the JMJD2C­induced decrease in the phosphorylation of ß­catenin. On the whole, the findings of the present study demonstrated that JMJD2C promotes the malignancy of MM via the activation of the ß­catenin pathway. These results suggested that JMJD2C may be a potential target for MM treatment.

Orthopedic Surgical Treatment and Perioperative Complications in Multiple Myeloma Bone Disease: Analysis of a Series (2009-2018).

BACKGROUND: More than 90% of patients with multiple myeloma (MM) develop lytic bone lesions that can be surgically treated for symptomatic relief and functional improvement. METHODS: This was a retrospective observational analytic study conducted between 2009 and 2018, including 58 patients with MM bone disease who underwent 77 orthopedic surgical procedures and were co-managed by internal medicine. Analysis of data related to MM bone disease, different modalities of surgical treatment, perioperative complications, and survival was performed. RESULTS: Median age was 72 years (66.5-77 years) and 56.9% of patients were males; 54.43% of injuries were located in the spine, 27.85% in the pelvis or lower limbs, 15.19% in the upper limbs, and 75.32% of patients had pathologic fractures. In 29.31% of the cases, the bone lesion was the debut of MM. Surgical procedures performed were mainly kyphoplasty (48.05%) and intramedullary nailing (29.87%). The overall complication rate following surgery was 74.03%. Only 20.78% of cases had a surgical complication. Among medical complications, we registered 28.57% transfusion requirements, 25.97% acute renal failures, 24.68% developed an infection, and 10.39% developed hypercalcemia. Patients were followed-up for a mean of 6.13 years and 37.93% suffered a new fracture. The median overall survival time for patients after surgery was 32.9 months (11.6-49). The estimated overall survival at 1, 3, and 5 years after surgery was 81.17%, 57%, and 34.11%, respectively. CONCLUSIONS: The orthopedic surgical treatment of MM bone disease aims to improve symptomatology and patient quality of life; however, these patients have a high risk of perioperative complications and considerable early mortality, making multidisciplinary management with medical specialties essential.

Front-line daratumumab-VTd versus standard-of-care in ASCT-eligible multiple myeloma: matching-adjusted indirect comparison.

Aim: To compare daratumumab plus standard-of-care (SoC; bortezomib/thalidomide/dexamethasone [VTd]) and VTd alone with other SoC for transplant-eligible newly diagnosed multiple myeloma. Patients & methods: We conducted an unanchored matching-adjusted indirect comparison of progression-free and overall survival (PFS/OS) with D-VTd/VTd versus bortezomib/lenalidomide/dexamethasone (VRd), bortezomib/cyclophosphamide/dexamethasone (VCd) and bortezomib/dexamethasone (Vd). Results: After matching adjustment, significant improvements in PFS were estimated for D-VTd versus VRd (hazard ratio [HR]: 0.47 [95% CI: 0.33-0.69]), VCd (HR: 0.35 [95% CI: 0.21-0.58]) and Vd (HR: 0.42 [95% CI: 0.28-0.63]). OS was significantly longer with D-VTd versus VRd (HR: 0.31 [95% CI: 0.16-0.57]), VCd (HR: 0.35 [95% CI: 0.14-0.86]) and Vd (HR: 0.38 [95% CI: 0.18-0.77]). No significant PFS/OS differences were seen for VTd versus other SoC. Conclusion: This analysis supports front-line daratumumab for transplant-eligible newly diagnosed multiple myeloma.