-
Leukemia Research Aug 2023Anti-CD38 monoclonal antibodies (mAbs) are commonly used for treating newly diagnosed and relapsed/refractory (r/r) multiple myeloma (MM). However, concerns have been... (Meta-Analysis)
Meta-Analysis
Anti-CD38 monoclonal antibodies (mAbs) are commonly used for treating newly diagnosed and relapsed/refractory (r/r) multiple myeloma (MM). However, concerns have been raised about the occurrence of second primary malignancies (SPMs) in patients receiving anti-CD38 mAbs. Assessing the safety data for rare adverse events like SPMs is challenging because individual clinical trials are typically focused on the primary endpoint. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) published between January 2005 and April 2022, including patients with newly diagnosed or r/r MM. Our aim was to compare SPM rate with the use of anti-CD38 mAb-based regimens with other anti-myeloma regimens. After a median follow-up of 35.3 months (range: 8.2-56.2), we found that exposure to anti-CD38 mAbs was associated with an increased risk of developing SPMs compared to the control group (6.8% vs. 5.2%; Peto odds ratio [OR]: 1.53 [95% confidence interval (CI): 1.20-1.95]; I= 0%, p-value for heterogeneity= 0.44). This increased risk was primarily driven by non-melanoma cutaneous cancers (92 vs. 47; Peto OR: 1.77 [95% CI: 1.25-2.51]; I = 0%, p-value for heterogeneity = 0.54). However, there was no significant difference in the incidence of solid tumors (including malignant melanoma) (OR: 1.28 [95% CI: 0.85-1.95]) or hematologic SPMs (OR: 1.86; [95% CI: 0.81-4.27]). In conclusion, the use of anti-CD38 mAb-based combination regimens is associated with a higher risk of non-invasive cutaneous SPMs, but not solid tumors or hematologic SPMs. The increased occurrence of non-invasive cutaneous SPMs may be due to enhanced monitoring resulting from longer treatment duration with anti-CD38 mAbs.
Topics: Humans; Multiple Myeloma; Neoplasms, Second Primary; Incidence; Antineoplastic Agents; Antibodies, Monoclonal
PubMed: 37285641
DOI: 10.1016/j.leukres.2023.107324 -
Medicina Oral, Patologia Oral Y Cirugia... Jul 2023Amyloidosis is a disease characterized by the progressive deposition of abnormal proteins that can occur in any organ. In the oral cavity, the tongue is the most common...
BACKGROUND
Amyloidosis is a disease characterized by the progressive deposition of abnormal proteins that can occur in any organ. In the oral cavity, the tongue is the most common affected site, usually causing macroglossia. Biopsy is essential for the diagnosis and the occurrence of its systemic form is mandatory to be investigated. This systematic review evaluated the existing information in the literature on Amyloidosis in the oral cavity to allow a more comprehensive and updated analysis of its clinicopathological characteristics, as well as to explore the main forms of treatment and prognostic factors.
MATERIAL AND METHODS
Electronic searches were undertaken in five databases supplemented by manual scrutiny.
RESULTS
A total of 111 studies were included with 158 individuals.
CONCLUSIONS
The disease had a higher prevalence in women, the tongue was the most affected site, as well as the systemic form of the disease. The worst prognosis was for cases of systemic amyloidosis associated with multiple myeloma.
Topics: Humans; Female; Amyloidosis; Macroglossia; Multiple Myeloma; Tongue Diseases; Tongue
PubMed: 37330968
DOI: 10.4317/medoral.25761 -
Journal of Orthopaedic Surgery and... Jun 2021To compare the efficacy and safety between denosumab and zoledronic acid for advanced cancer with bone metastasis. (Meta-Analysis)
Meta-Analysis
Comparison of denosumab and zoledronic acid for the treatment of solid tumors and multiple myeloma with bone metastasis: a systematic review and meta-analysis based on randomized controlled trials.
OBJECTIVE
To compare the efficacy and safety between denosumab and zoledronic acid for advanced cancer with bone metastasis.
METHODS
MEDLINE, EMBASE, and the Cochrane library databases were searched for randomized controlled trials up to December 2020 that compared denosumab and zoledronic acid in the treatment of advanced cancer with bone metastasis. The following clinical outcomes were extracted for analysis: time to first skeletal-related event, time to first-and-subsequent skeletal-related events, overall survival, and disease progression. Safety outcomes including incidence of adverse events, serious adverse events, acute-phase reactions, renal toxicity, osteonecrosis of the jaw, and hypocalcemia were also extracted.
RESULTS
Four randomized controlled trials involving 7201 patients were included. The overall analysis showed that denosumab was superior to zoledronic acid in delaying time to first skeletal-related event (hazard ratio = 0.86; 95% confidence interval, 0.80-0.93; P < 0.01) and time to first-and-subsequent skeletal-related events (risk ratio 0.87; 95% confidence interval 0.81-0.93; P < 0.01). Denosumab was associated with lower incidence of renal toxicity (risk ratio 0.69; 95% confidence interval 0.54-0.87; P < 0.01) and acute phase reaction (risk ratio 0.47; 95% confidence interval 0.38-0.56; P < 0.01), but higher incidence of hypocalcemia (risk ratio 1.78; 95% confidence interval 1.33-2.38; P < 0.01) and osteonecrosis of the jaw (risk ratio 1.41; 95% confidence interval 1.01-1.95; P = 0.04). No significant differences were found in overall survival, time to disease progression, or incidence of adverse events and serious adverse events between denosumab and zoledronic acid.
CONCLUSIONS
Compared with zoledronic acid, denosumab is associated with delayed first-and-subsequent skeletal-related events, lower incidence of renal toxicity, and acute phase reaction, but higher incidence of hypocalcemia and osteonecrosis of the jaw. Hence, denosumab seems to be a promising choice for advanced cancer with bone metastasis. Nonetheless, more randomized controlled trials are needed for further evaluation.
Topics: Bone Density Conservation Agents; Bone Neoplasms; Denosumab; Humans; Multiple Myeloma; Plasmacytoma; Randomized Controlled Trials as Topic; Treatment Outcome; Zoledronic Acid
PubMed: 34158101
DOI: 10.1186/s13018-021-02554-8 -
The Journal of International Medical... Aug 2021To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM).
METHODS
A systematic search of publications listed on electronic databases (PubMed®, The Cochrane Library, Science Direct and Web of Science) between inception and 13 November 2020 was conducted to find randomized controlled trials (RCTs) that included patients with MM that were treated with combination regimens containing daratumumab.
RESULTS
A total of seven RCTs were included ( = 4268 patients). Meta-analysis showed that compared with the control group, the group containing daratumumab showed a significantly better overall response rate and a complete response or better. Daratumumab improved efficacy in both standard-risk and cytogenetically high-risk patients with MM. The prevalence of neutropenia (≥grade 3) and pneumonia was significantly higher in the daratumumab group compared with the control group.
CONCLUSION
The available evidence demonstrated that the clinical application of combination regimens containing daratumumab improved the efficacy in patients with MM and had acceptable safety.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Humans; Multiple Myeloma; Neutropenia
PubMed: 34433331
DOI: 10.1177/03000605211038135 -
Hematology (Amsterdam, Netherlands) Jan 2015The aim of this systematic review was to evaluate the efficacy and safety of targeted agents used as monotherapy or combined therapy in patients with relapsed/refractory... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The aim of this systematic review was to evaluate the efficacy and safety of targeted agents used as monotherapy or combined therapy in patients with relapsed/refractory multiple myeloma (MM).
METHODS
The systematic literature search was conducted in PubMed, Embase, Cochrane Library till 27 May 2013.
RESULTS
Four randomized controlled trials were included. The meta-analysis showed that combined therapy significantly improved progression-free survival compared with monotherapy (P < 0.05). However, there was not a significant difference between monotherapy and combined therapy in overall survival (P > 0.05). The combined therapy also significantly increased the risk of serious adverse events and grade 3/4 AEs compared to monotherapy (P < 0.05). Overall, the results of comparisons between monotherapy and combined therapy in individual trials were differentiated, and some combinations were not more effective than monotherapy (bortezomib plub bevacizumab vs. bortezomib and thalidomide plus INFα vs. thalidomide) which emphasizes the role of individualized therapy in relapsed/refractory MM especially in the elderly or patients with significant comorbidities.
CONCLUSIONS
The results of this meta-analysis showed that combined therapy is superior to monotherapy only in some end points and it is less tolerated in patients with relapsed/refractory MM. Thus, the overall superiority of complex therapy to monotherapy depends on the combination of the targeted agents.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Molecular Targeted Therapy; Multiple Myeloma; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic
PubMed: 24580409
DOI: 10.1179/1607845414Y.0000000159 -
Journal of the National Cancer Institute Mar 2016Immunomodulatory drugs (IMiDs) and proteasome inhibitors have dramatically changed management of multiple myeloma (MM). While MM remains incurable, consolidation and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immunomodulatory drugs (IMiDs) and proteasome inhibitors have dramatically changed management of multiple myeloma (MM). While MM remains incurable, consolidation and maintenance therapy aimed at improving duration of response can potentially improve survival outcomes. A majority of randomized controlled trials (RCTs) have demonstrated benefit of IMiD-based maintenance therapy in delaying disease progression; however, whether this therapy can lead to improved survival remains controversial.
METHODS
PubMed and abstract databases of major hematology and/or oncology meetings were searched for RCTs that studied maintenance therapy with IMiDs in MM. A meta-analysis was conducted to systematically evaluate the impact of IMiD-based maintenance therapy on survival outcomes and serious adverse events associated with the therapy. All statistical tests were two-sided.
RESULTS
Eighteen phase 3 RCTs enrolling 7730 patients were included. IMiD-based maintenance therapy statistically significantly prolonged progression-free survival (PFS; hazard ratio (HR) = 0.62, 95% confidence interval (CI) = 0.57 to 0.67, P < .001) but failed to improve overall survival (OS; HR = 0.93, 95% CI = 0.85 to 1.01, P = .082). Stratified analyses demonstrated that both thalidomide and lenalidomide provided PFS but not OS benefit in transplantation as well as nontransplantation settings. IMiD-based maintenance therapy in MM led to a higher risk of grade 3-4 thromboembolism (risk ratio = 2.52, 95% CI = 1.41 to 4.52, P = .002). Thalidomide maintenance therapy increased the risk of peripheral neuropathy; lenalidomide maintenance therapy increased the risks of myelosuppression and second primary hematological malignancies.
CONCLUSIONS
Thalidomide- or lenalidomide-based maintenance therapy improves PFS but not OS in MM and increases risks of grade 3-4 adverse events, including thromboembolism, peripheral neuropathy, neutropenia, and infection.
Topics: Disease-Free Survival; Humans; Immunosuppressive Agents; Infections; Lenalidomide; Maintenance Chemotherapy; Multiple Myeloma; Neoplasms, Second Primary; Neutropenia; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Risk; Severity of Illness Index; Survival Analysis; Survival Rate; Thalidomide; Thromboembolism
PubMed: 26582244
DOI: 10.1093/jnci/djv342 -
Oncology Research and Treatment 2015Demonstrating improved overall survival (OS) with new multiple myeloma (MM) treatments is becoming difficult because of extended survival, so progression-free survival... (Meta-Analysis)
Meta-Analysis Review
Relationship between treatment effects on progression-free survival and overall survival in multiple myeloma: a systematic review and meta-analysis of published clinical trial data.
BACKGROUND
Demonstrating improved overall survival (OS) with new multiple myeloma (MM) treatments is becoming difficult because of extended survival, so progression-free survival (PFS) is commonly used as a surrogate endpoint for OS. We evaluated PFS as a potential surrogate for OS by examining whether observed treatment effects on PFS are positively associated with treatment effects on OS in MM.
METHODS
A systematic literature review identified 21 randomized control trials reporting hazard ratios (HRs) for treatment effects on PFS and OS. Pearson's r estimated the relationship between HRs (HRPFS and HROS), and between log-transformed HRs (log(HRPFS) and log(HROS)). R(2) values were estimated from linear regression models of the HR and the log(HR) relationships. Sensitivity and subgroup analyses examined the robustness of the HR findings.
RESULTS
Positive correlations were found between HRPFS and HROS (r = 0.82; p < 0.0001) and between log(HRPFS) and log(HROS) (r = 0.80; p < 0.0001). Linear regression models produced R(2) values of 0.67 and 0.63 when regressing HROS on HRPFS, and log(HROS) on log(HRPFS), respectively. Sensitivity analyses supported the HR findings.
CONCLUSION
This analysis provides evidence for a positive association between treatment effects on PFS and OS. Studies involving patient level data are necessary to confirm whether PFS is a valid surrogate for OS in MM.
Topics: Antineoplastic Agents; Disease-Free Survival; Multiple Myeloma; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome
PubMed: 25792079
DOI: 10.1159/000375392 -
American Journal of Hematology Jun 2024Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease... (Meta-Analysis)
Meta-Analysis Comparative Study
Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta-analysis.
Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive about the differential thrombogenicity of carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/lenalidomide/dexamethasone (VRd). This meta-analysis compares the risk for venous thromboembolism (VTE; including deep venous thrombosis and pulmonary embolism) and arterial thromboembolism (ATE; including myocardial infarction and ischemic stroke) with KRd versus VRd as primary therapy for newly diagnosed MM (NDMM). Out of 510 studies identified after deduplication, one randomized controlled trial and five retrospective cohort studies were included. We analyzed 2304 patients (VRd: 1380; KRd: 924) for VTE events and 2179 patients (VRd: 1316; KRd: 863) for ATE events. Lower rates of VTE were observed in the VRd group when compared with the KRd group (6.16% vs. 8.87%; odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.88; p = .01). Both treatment groups exhibited minimal ATE incidence, with no significant difference between them (0.91% vs. 1.16%; OR, 1.01; 95% CI, 0.24-4.20; p = .99). In view of potential biases from retrospective studies, heterogeneity of baseline population characteristics, and limited access to patient-level data (e.g., VTE risk stratification and type of thromboprophylaxis regimen used) inherent to this meta-analysis, additional research is warranted to further validate our findings and refine strategies for thrombosis prevention in MM.
Topics: Humans; Multiple Myeloma; Dexamethasone; Oligopeptides; Bortezomib; Antineoplastic Combined Chemotherapy Protocols; Lenalidomide; Thromboembolism; Venous Thromboembolism
PubMed: 38488702
DOI: 10.1002/ajh.27288 -
Clinical Lymphoma, Myeloma & Leukemia Oct 2020Waldenström macroglobulinemia (WM) is an IgM-producing lymphoproliferative disorder that remains incurable. Patients with high-risk disease have an overall survival... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Waldenström macroglobulinemia (WM) is an IgM-producing lymphoproliferative disorder that remains incurable. Patients with high-risk disease have an overall survival (OS) of less than 3 years. Both autologous (AHCT) and allogeneic (allo-HCT) hematopoietic cell transplantation (HCT) are prescribed for treatment of WM despite a lack of randomized controlled studies.
MATERIALS AND METHODS
We performed a comprehensive literature search using PubMed/Medline and EMBASE on September 10, 2019. Data on clinical outcomes related to benefits and harms was extracted independently by 3 authors. Fifteen studies (8 AHCT [n = 278 patients], 7 allo-HCT [n = 311 patients]) were included in this systematic review/meta-analysis.
RESULTS
Pooled OS, progression-free survival (PFS), and nonrelapse mortality (NRM) rates post AHCT were 76% (95% confidence interval [CI], 65%-86%), 55% (95% CI, 42%-68%), and 4% (95% CI, 1%-7%), respectively. Pooled OS, PFS, and NRM rates post allografting were 57% (95% CI, 50%-65%), 49% (95% CI, 42%-56%), and 29% (95% CI, 23%-34%), respectively. OS and PFS rates were reported at 3 to 5 years, and NRM was reported at 1 year in most studies. Pooled ORR (at day 100) post AHCT and allo-HCT were 85% (95% CI, 72%-94%) and 81% (95% CI, 69%-91%), respectively. Pooled complete response rates post AHCT and allo-HCT were 22% (95% CI, 17%-28%) and 26% (95% CI, 7%-50%), respectively. Relapse rates post AHCT and allo-HCT were 42% (95% CI, 30%-55%) and 23% (95% CI, 18%-28%), respectively.
CONCLUSIONS
Our results show that both AHCT and allo-HCT are effective in the treatment of WM. A 2-fold lower relapse rate but a 7-fold higher NRM was noted for allo-HCT compared with AHCT. The role of transplant in WM needs to be addressed in the era of novel agents.
Topics: Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Transplantation Conditioning; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome; Waldenstrom Macroglobulinemia
PubMed: 32616401
DOI: 10.1016/j.clml.2020.05.021 -
Pituitary Jun 2017Parasellar plasmacytomas are rare tumors localized to the sellar region arising from plasma cells. Knowledge of clinical, imaging, surgical, and pathological... (Review)
Review
PURPOSE
Parasellar plasmacytomas are rare tumors localized to the sellar region arising from plasma cells. Knowledge of clinical, imaging, surgical, and pathological characteristics is limited to single case reports.
METHODS
A retrospective analysis of five primary cases was conducted, followed by systematic review of English language articles using PubMed in accordance with PRISMA guidelines.
RESULTS
Five primary case patients include four men and one woman, ages 60-77, followed up to 3 years. A systematic review identified 65 additional patients, of whom 65% presented with cranial nerve palsies and 15% with hypopituitarism. Sixteen percent had history of known multiple myeloma (MM) while 37% were diagnosed concurrently with MM on presentation of parasellar plasmacytoma. Imaging showed median tumor size of 38 mm (range, 4-70 mm), with MRI intensity similar to that of other sellar masses. Surgical biopsy with immunohistochemical studies confirmed plasmacytoma diagnosis. Eighty-one percent underwent parasellar radiotherapy, and chemotherapy initiated in 59% of the 69 patients with MM. Overall survival rate was 74% at follow-up (median 12 months), with 18% having parasellar recurrences and 38% progressing to systemic MM after presentation of a solitary plasmacytoma (median 3 months).
CONCLUSIONS
Parasellar plasmacytomas are rare tumors that should be considered in the differential diagnosis for lesions involving the sella and arising from the clivus, especially when cranial nerve paresis is apparent, even in the absence of known MM. Although recurrence rates for parasellar plasmacytoma is low, patients should be monitored for progression to MM. Treatment depends on the presence of systemic disease at diagnosis.
Topics: Aged; Female; Humans; Male; Multiple Myeloma; Plasmacytoma; Retrospective Studies
PubMed: 28251542
DOI: 10.1007/s11102-017-0799-5