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Pharmacological Research Apr 2023Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell... (Meta-Analysis)
Meta-Analysis Review
Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell therapy is currently being used for the treatment of relapsed/refractory (r/r) B-cell malignancies including Acute Lymphoblastic Leukemia, Large B-Cell Lymphoma, Follicular Lymphoma, Multiple Myeloma and Mantle Cell Lymphoma. Despite the unprecedented clinical success, one of the major issues of the approved CAR-T cell therapy - tisagenlecleucel, axicabtagene, lisocabtagene, idecabtagene, ciltacabtagene and brexucabtagene - is the uncertainty about its persistence which in turn could lead to weak or no response to therapy with malignancy recurrence. Here we show that the prognosis of patients who do not respond to CAR-T cell therapy is still an unmet medical need. We performed a systematic review and meta-analysis collecting individual data on Duration of Response from at least 12-month follow-up studies. We found that the pooled prevalence of relapse within the first 12 months after CAR-T infusion was 61% (95% CI, 43%-78%); moreover, one year after the infusion, the analysis highlighted a pooled prevalence of relapse of 24% (95% CI, 11%-42%). Our results suggest that identifying potential predictive biomarkers of response to CAR-T therapy, especially for patients affected by the advanced stage of blood malignancies, could lead to stratification of the eligible population to that therapy, recognizing which patients will benefit and which will not, helping regulators to make decision in that way.
Topics: Humans; Adult; Receptors, Chimeric Antigen; T-Lymphocytes; Hematologic Neoplasms; Chronic Disease; Multiple Myeloma; Recurrence; Cell- and Tissue-Based Therapy
PubMed: 36963592
DOI: 10.1016/j.phrs.2023.106742 -
Hematology (Amsterdam, Netherlands) Dec 2023Multiple myeloma (MM) remains an incurable disease despite advances in treatment options. Recently, selinexor has shown promising efficacy for relapsed/refractory... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Multiple myeloma (MM) remains an incurable disease despite advances in treatment options. Recently, selinexor has shown promising efficacy for relapsed/refractory multiple myeloma (RRMM), whereas its optimal timing and drug combination remain unclear. In order to assess the various regimens that incorporate selinexor, a systematic review and meta-analysis was conducted.
METHODS
Clinical trials and real-world studies involving MM patients treated with selinexor were included. Pooled risk ratio (RR) was calculated to compare the rates, along with a 95% confidence interval (CI) and concurrent -value assessment. A random-effects model was employed to provide a more conservative evaluation.
RESULTS
A total of 16 studies enrolling 817 patients were reviewed. The usage of selinexor as the fifth-line or prior therapy achieved a higher objective response rate (ORR) (65.9% versus 23.4%, < 0.01) and longer pooled progression-free survival (PFS) (median: 12.5 months versus 2.9 months, < 0.01) than those after the fifth-line usage. In addition, early usage also resulted in a consistent trend of pooled overall survival (median: 22.7 months versus 8.9 months, = 0.26), compared with post-fifth-line usage. Selinexor and dexamethasone (Xd) plus either protease inhibitors (PIs) or immunomodulatory drugs (IMiDs) achieved better ORRs than the Xd-only regimen for RRMM, with ORRs of 56.1%, 52.5% and 24.6%, respectively (< 0.01).
CONCLUSION
In conclusion, using selinexor as the fifth-line or prior therapy had a beneficial impact on RRMM. The regimen of Xd plus PIs or IMiDs was recommended.
Topics: Humans; Multiple Myeloma; Immunomodulating Agents; Dexamethasone; Drug Combinations; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36920065
DOI: 10.1080/16078454.2023.2187972 -
Annals of Medicine Dec 2023Multiple myeloma (MM) is an incurable malignancy. Venetoclax (VEN) shows a meaningful effect in MM patients who are relapsed or refractory (RR) to previous standard... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple myeloma (MM) is an incurable malignancy. Venetoclax (VEN) shows a meaningful effect in MM patients who are relapsed or refractory (RR) to previous standard therapies.
OBJECTIVE
This study aimed to assess the efficacy and safety of VEN-based treatments in RR MM patients.
MATERIALS AND METHODS
Comprehensive studies were searched in PubMed, Embase, Web of Science and Cochrane library. Efficacy was assessed by overall response rate (ORR), strict complete response rate (sCR), complete response rate (CR), very good partial response rate (VGPR) and partial response rate (PR).
RESULTS
Seven studies containing 482 subjests were included. The pooled ORR, ≥ CR (sCR + CR), VGPR and PR were 68% (51%-85%), 24% (13%-35%), 25% (17%-34%) and 17% (11%-24%) respectively. Multi-drug treatments were superior to VEN ± dexamethasone (Dex) treatments in ORR (82% vs 42%, = .003) and ≥ CR (36% vs 7%, < 0.00001). Subgroup analysis indicated patients achieve higher ORR who harboring t(11;14) translocation or containing high BCL-2 expression.
CONCLUSIONS
VEN-containing regimens could be suggested as effective and safe treatments to RR MM patients with t(11;14) or high BCL-2 levels.
Topics: Humans; Multiple Myeloma; Prospective Studies; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 36911885
DOI: 10.1080/07853890.2023.2186480 -
Georgian Medical News Dec 2022Many experimental studies have investigated various treatment options for patients with multiple myeloma; however, bortezomib, lenalidomide, dexamethasone (RVD regimen)...
Many experimental studies have investigated various treatment options for patients with multiple myeloma; however, bortezomib, lenalidomide, dexamethasone (RVD regimen) is still considered a gold-standard therapy. This regimen can lead to a wide range of side effects, one of which is enterotoxicity. Significantly efficacious enteroprotective interventions have not yet been developed or implemented into clinical practice. This literature review assesses the development of chemotherapy-driven dysbiosis through Toll-like receptors (TLRs) and explores the hypothesis that the gut microbiome could provide significant enteroprotection. A systematic review was performed by utilizing articles published between 2015-2022 from the following databases: Medical Literature Analysis and Retrieval System Online (Medline), PubMed, Science Direct, and Cochrane Library databases. In conclusion, we found further studies of gut microbiome variety and function are necessary and could be used in development of treatment and prevention strategy of chemotherapy enterotoxicity.
Topics: Humans; Multiple Myeloma; Dysbiosis; Antineoplastic Combined Chemotherapy Protocols; Lenalidomide; Bortezomib
PubMed: 36780619
DOI: No ID Found -
International Immunopharmacology Jan 2023Multiple myeloma (MM) is the second most common hematological malignancy without cure, and Chimeric Antigen Receptor T Cell (CAR-T) therapy has been shown great...
BACKGROUND
Multiple myeloma (MM) is the second most common hematological malignancy without cure, and Chimeric Antigen Receptor T Cell (CAR-T) therapy has been shown great promising in MM. Unlike previous published studies mainly focusing on efficacy and safety, this study aims to summarize time points in the process of CAR-T therapy in MM and establish a standardized time-related CAR-T therapy platform to provide a reference for CAR-T treatment in MM.
METHODS
All the literatures were retrieved from PubMed, Web of Science, Embase, American Society of Hematology (ASH), American Society of Clinical Oncology (ASCO) and European Hematology Association (EHA). Relevant median detection time of efficacy and safety-related indicators of CAR-T therapy in MM were extracted from included literatures, and median values were applied to represent detection time points of indicators. Notably, the median values were not the certain and optimal detection time points, while the significance is that indicators could be detected more frequently around the median values to obtain the ideal results.
RESULTS
This review presented the median detection time points of efficacy and safety-related indicators of CAR-T therapy in MM according to the chronological order. For short-term effects on inflammation status within 1 month after CAR-T initiation, the median time points of cytokine release syndrome onset, immune effector cell-associated neurotoxicity syndrome onset, neutrophils recovery and CAR-T expansion peak were 4.5, 8, 10 and 12 days, respectively. For medium-term effects on clinical response in MM beyond 1 month and up to 3 months following CAR-T infusion, the median time points of minimal residual disease negativity, the reduction of serum light chain to minimum, platelet recovery and the reduction of M protein to minimum were 30, 30, 44 and 90 days, respectively.
CONCLUSIONS
This systematic review summarized the median detection time points of efficacy and safety-related indicators of CAR-T therapy in MM and constructed the time-related CAR-T therapy platform, providing an evidence-based standard for establishment of CAR-T treatment regimen in MM.
Topics: Humans; Multiple Myeloma; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Immunotherapy; T-Lymphocytes
PubMed: 36700772
DOI: 10.1016/j.intimp.2022.109592 -
British Journal of Haematology Mar 2023The prognosis of multiple myeloma (MM) has dramatically improved with the development of new drugs, and it has become important to determine the appropriate combinations... (Meta-Analysis)
Meta-Analysis Review
The prognosis of multiple myeloma (MM) has dramatically improved with the development of new drugs, and it has become important to determine the appropriate combinations of these novel agents. This study was a systematic review and network meta-analysis (NMA) of randomized trials in patients with relapsed and/or refractory (RR) MM. The PubMed, Cochrane, and Embase databases were searched for randomized trials from 1 January 2002 to 28 February 2022 of patients treated for MM. The primary end-point was progression-free survival (PFS), evaluated as a hazard ratio (HR) with a 95% confidence interval (95% CI) compared to dexamethasone (DEX). The p-score was used to rank treatments. Of a total of 1136 abstracts screened, 37 studies were selected, including 34 treatment options for RRMM. Daratumumab, lenalidomide and DEX was found to be the best treatment for RRMM, with the best HR compared to DEX (HR, 0.13; 95% CI, 0.08-0.20; p-score 0.9796). There was no evidence of significant heterogeneity (I , 41.3%; p = 0.146). The current NMA confirmed the excellent efficacy of three-drug regimens including anti-CD38 antibodies to treat RRMM and provides background data to evaluate the efficacy of chimeric antigen receptor T-cell treatments and bispecific T-cell engager therapies.
Topics: Humans; Multiple Myeloma; Network Meta-Analysis; Antineoplastic Combined Chemotherapy Protocols; Lenalidomide; Progression-Free Survival; Dexamethasone
PubMed: 36661264
DOI: 10.1111/bjh.18654 -
The Journal of the American Academy of... Feb 2023The Musculoskeletal Tumor Society, in partnership with American Society of Clinical Oncology and American Society for Radiation Oncology, has developed a clinical...
The Musculoskeletal Tumor Society, in partnership with American Society of Clinical Oncology and American Society for Radiation Oncology, has developed a clinical practice guideline to assist providers with the care of patients with metastatic carcinoma and myeloma of the femur. The guideline was developed by an Expert Panel consisting of representatives of all three organizations by American Academy of Orthopaedic Surgeons (AAOS) methodologists using the AAOS standardized guideline development process. A systematic review of the available evidence was conducted, and the identified evidence was rated was rated for quality and potential for bias. Recommendations were developed based on this evidence in a standardized fashion. The guideline was approved by the guideline approval bodies of all three organizations. Thirteen recommendations were synthesized covering relevant subtopics such as imaging, use of bone-modifying agents, radiation therapy, and surgical reconstruction. The consensus of the expert panel was that bone-modifying agents may assist in reducing the incidence of femur fracture, regardless of tumor histology. The panel recommended the use of radiation therapy to decrease the rate of femur fractures for patients considered at increased risk. The panel recommended arthroplasty be considered to improve patient function and decrease the need of postoperative radiation therapy in patients with pathologic fractures in the femur.
Topics: Humans; United States; Multiple Myeloma; Orthopedic Surgeons; Radiation Oncology; Carcinoma; Femur
PubMed: 36656274
DOI: 10.5435/JAAOS-D-21-00888 -
Journal of Cancer Survivorship :... Jun 2024Patients with relapse and/or refractory multiple myeloma (RRMM) have a high disease burden with poor health-related quality of life (HRQoL) which worsens with each... (Review)
Review
The impact of current therapeutic options on the health-related quality of life of patients with relapse/refractory multiple myeloma: a systematic review of clinical studies.
PURPOSE
Patients with relapse and/or refractory multiple myeloma (RRMM) have a high disease burden with poor health-related quality of life (HRQoL) which worsens with each additional relapse. We aimed to review the impact of triplet, doublet, monotherapies, and salvage autologous stem cell transplantation on the HRQoL of RRMM patients.
METHODS
We performed a comprehensive literature search of Medline/PubMed, Wiley Cochrane Library, EMBASE, Scopus, CINAHL, and Clinicaltrials.gov to identify clinical studies in RRMM patients with HRQoL as an outcome measure. The ISOQoL and CONSORT-PRO extension guidelines were used to assess the quality of HRQoL reporting. We synthesized the result using a qualitative analysis.
RESULTS
A total of 10,245 RRMM patients enrolled in 28 eligible studies received either a triplet, doublet regimen, monotherapy, or salvage autologous stem cell transplantation. The EORTC QLQ-C30 was the most used questionnaire, and compliance with HRQoL reporting standards is generally poor among studies without an additional HRQoL publication. Most of the current therapeutic options are at best able to maintain HRQoL at baseline but not improve it. The methodological and reporting heterogeneity among the studies complicates generalizations.
CONCLUSIONS
Many of the current treatment regimens for RRMM have demonstrated clinical effectiveness in trials. Unlike newly diagnosed MM, these regimens are less likely to result in significant improvement in HRQoL in RRMM. This should be communicated to patients before initiating therapies.
IMPLICATIONS FOR CANCER SURVIVORS
Individualized therapeutic approach for RRMM should be chosen based on a shared decision-making process that aligns clinical efficacy with patients' treatment priorities and HRQoL.
Topics: Multiple Myeloma; Humans; Quality of Life; Neoplasm Recurrence, Local; Transplantation, Autologous
PubMed: 36645615
DOI: 10.1007/s11764-023-01332-1 -
Expert Review of Anticancer Therapy Mar 2023We evaluate the efficacy and safety of Elotuzumab, an immunostimulatory monoclonal antibody, in combination with concomitant treatment regimens for multiple myeloma (MM)... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We evaluate the efficacy and safety of Elotuzumab, an immunostimulatory monoclonal antibody, in combination with concomitant treatment regimens for multiple myeloma (MM) patients.
RESEARCH DESIGN AND METHODS
PubMed, Scopus, Web of Science, and EMBASE databases were searched systematically up to 2 August 2022.
RESULTS
Five randomized control trials with a total of 1,763 participants were included. Elotuzumab combination therapy improved PFS and OS by 14% (hazard ratio [HR] 0.86) and 20% (HR 0.80), respectively, relative to the non-Elotuzumab regimen. Adding Elotuzumab to Lenalidomide plus Dexamethasone regimen (HR 0.82) or Pomalidomide plus Dexamethasone regimen (HR 0.54) were considered to improve the PFS. Meanwhile, the risk of disease progression was only reduced for patients with relapsed/refractory MM (HR 0.70) but not for newly diagnosed/untreated MM (HR 0.93). Finally, the risk of serious adverse events (RR 1.12) and the risk of infection (RR 1.09) and cardiac disorders (RR 1.32) were higher for the experimental group compared to the control group.
CONCLUSIONS
Our findings showed that Elotuzumab combination therapy prolonged OS and PFS compared to non-Elotuzumab treatments in patients with MM. However, further investigations are required to establish the most effective combination of the Elotuzumab regimen.
Topics: Humans; Multiple Myeloma; Dexamethasone; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Antibodies, Monoclonal; Randomized Controlled Trials as Topic
PubMed: 36638778
DOI: 10.1080/14737140.2023.2169139 -
Medicine Jan 2023Nasal extramedullary plasmacytoma (EMP) is a rare plasma cell tumor that occurs in the soft tissue of the nasal cavity, and its imaging characteristics are still...
Nasal extramedullary plasmacytoma (EMP) is a rare plasma cell tumor that occurs in the soft tissue of the nasal cavity, and its imaging characteristics are still unclear. The purpose of this study was to investigate the clinical features, imaging findings, treatment, survival analysis, and prognosis of nasal EMP, and to provide a systematic review of the patients we treated and the published literature. A 45-year-old female patient who presented with epistaxis with nasal obstruction was recommended for magnetic resonance imaging to assess the nature of the lesion. On magnetic resonance imaging, abnormal signal shadow can be seen in the right nasal cavity. Diffusion weighted imaging showed signal of the lesion was significantly limited, presenting high signal, with a low apparent dispersion coefficient, and the lesion was significantly enhanced on contrast-enhanced scan. Combined with the clinical manifestations of the patient, who was initially considered to have a hemangioma. She underwent endoscopic nasal surgery under general anesthesia to remove the mass, and the final pathology confirmed it was EMP. However, the final pathology confirmed EMP. Five months later, the patient came to our hospital for follow-up and underwent fluorine-18-fluorodeoxyglucose/positron emission tomography/computed tomography scan, which showed no recurrence of the lesion and no transformation of multiple myeloma. The nasal EMP imaging findings were mostly soft tissue masses with uniform density or signal, which were significantly enhanced by enhancement scan, high signal on diffusion weighted imaging and low signal on apparent dispersion coefficient. Immunohistochemical staining for CD38, CD138, and CD79a was positive in most of the cases evaluated, while CD20 and CD10 were negative. The absence of dilated features, infiltrative features and the presence of significant contrast enhancement may be relatively specific imaging findings of nasal EMP. The prognosis of nasal EMP is good, and recurrence, metastasis, and transformation into multiple myeloma are rare. Because the lesions are sensitive to radiotherapy, surgical resection combined with radiotherapy is a more effective treatment.
Topics: Female; Humans; Middle Aged; Plasmacytoma; Multiple Myeloma; Nasal Cavity; Prognosis; Epistaxis
PubMed: 36637932
DOI: 10.1097/MD.0000000000032647