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European Review For Medical and... Nov 2022Triplet regimens based on pomalidomide and dexamethasone have been applied to treat relapsed/refractory multiple myeloma, but the safety and efficacy are not yet very... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of triplet regimens based on pomalidomide and dexamethasone for treatment of relapsed/refractory multiple myeloma: a systematic review and meta-analysis.
OBJECTIVE
Triplet regimens based on pomalidomide and dexamethasone have been applied to treat relapsed/refractory multiple myeloma, but the safety and efficacy are not yet very clear. This meta-analysis aimed at comparing the safety and efficacy of different triplet therapies and analyzing the best therapy regimen.
MATERIALS AND METHODS
A comprehensive literature search identified a total of 615 studies, and 22 studies assessing 1,889 subjects met the inclusion criteria of this meta: phase II/III trial, over 2 median lines of prior therapy, and detailed efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival (PFS). All statistical analyses were performed by Revman version 5.3, and the heterogeneity was tested by I2 (25% indicating low heterogeneity, 50% moderate, and 75% high). For those with less heterogeneity, fixed-effect model was used. With a significant high heterogeneity, a random-effect model was used.
RESULTS
Pooled analysis showed ORR 66.2% across all triplet regimens based on pomalidomide and dexamethasone. Among all triplet regimens, therapy containing bortezomib showed the highest ORR (90.3%), and the one containing elotuzumab showed the lowest ORR (41.2%). The pooled ORRs for the remaining treatment regimens are as follows: cyclophosphamide (70.1%), isatuximab (66.3%), daratumumab (61.2%), clarithromycin (60.0%), pembrolizumab (47.3%). A total of 21 adverse events appeared in the included studies, with neutropenia being the highest incidence of hematologic adverse events (32.1%) and cough being the highest incidence of non-hematologic adverse events (43.3.%).
CONCLUSIONS
Three-drug regimens based on pomalidomide and dexamethasone could yield excellent overall response rate to relapsed/refractory multiple myeloma, but there are still various adverse events; therefore, consequent studies should address these adverse events.
Topics: Humans; Multiple Myeloma; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Thalidomide
PubMed: 36394758
DOI: 10.26355/eurrev_202211_30162 -
Annals of Hematology Dec 2022With the incorporation of novel agents in earlier lines of therapy, an increasing number of multiple myeloma patients are refractory to traditional classes of drugs.... (Review)
Review
With the incorporation of novel agents in earlier lines of therapy, an increasing number of multiple myeloma patients are refractory to traditional classes of drugs. Selinexor in combination with dexamethasone has emerged as a viable option for heavily pretreated triple-class relapsed and refractory multiple myeloma (RRMM). In this systematic review, we analyzed available literature on the role of selinexor in RRMM. The Boston trial demonstrated that selinexor when combined with dexamethasone and bortezomib is associated with a better depth and duration of response without excessive toxicity, compared with bortezomib and dexamethasone alone. Similarly, selinexor in combination with carfilzomib and dexamethasone was found to have a durable response and tolerable safety profile in both carfilzomib-naive and carfilzomib refractory RRMM patients. Selinexor in combination with IMiDs (lenalidomide and pomalidomide) as well as CD38 monoclonal antibodies (daratumumab) also have promising results. Selinexor combination therapy is both safe and effective for patients with pretreated RRMM.
Topics: Humans; Multiple Myeloma; Bortezomib; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Neoplasm Recurrence, Local
PubMed: 36214853
DOI: 10.1007/s00277-022-04999-1 -
Expert Review of Hematology 2024To evaluate the efficacy and safety of pomalidomide in combination treatment of relapsed/refractory multiple myeloma (RRMM). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To evaluate the efficacy and safety of pomalidomide in combination treatment of relapsed/refractory multiple myeloma (RRMM).
METHODS
Published clinical trials were searched in the Cochrane Library, PubMed, EMBASE to February 2023. The literature was screened and evaluated according to the inclusion criteria, and the data were analyzed by a random effect model. Overall response rate (ORR), overall survival (OS), progression-free survival (PFS) and full grade or ≥ 3 adverse events (AEs) were the outcomes.
RESULTS
This study included 31 clinical trials, which included 4776 patients. The pooled ORR of the doublet regimens was 33.3% (95%CI: 27-39%) and the triplet regimens was 66% (95%CI: 58-74%). Among the 25 included studies, the median PFS was 8.29 months (95%CI: 7.27-9.31), and nine studies reported median OS of 19.43 months (95%CI: 14.56-24.30). In terms of safety, the most common hematologic AEs of grade ≥ 3 were neutropenia (41%) and anemia (20%); Non-hematologic AEs were pneumonia (14%) and infection/febrile neutropenia (14%).
CONCLUSIONS
Pomalidomide combined treatment regimens have shown good clinical efficacy, especially in pomalidomide + dexamethasone combined with other drugs. In terms of safety, it's important to pay attention to the likelihood of hematological adverse events when used clinically.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO: CRD42023420644.
Topics: Multiple Myeloma; Humans; Thalidomide; Dexamethasone; Antineoplastic Combined Chemotherapy Protocols; Recurrence; Treatment Outcome
PubMed: 38421372
DOI: 10.1080/17474086.2024.2326219 -
Journal of Cancer 2017In this work, we aim to further analyze the effect of pomalidomide for relapsed and/or refractory multiple myeloma (RRMM). A systematic literature search of PubMed,...
In this work, we aim to further analyze the effect of pomalidomide for relapsed and/or refractory multiple myeloma (RRMM). A systematic literature search of PubMed, MEDLINE and EMBASE was conducted on September 20, 2016. Pooled effect size (ES) with corresponding 95% confidence intervals (CIs) were calculated using random-effects model. STATA software (version 12.0; Stata Corporation; College Station, TX, USA) was employed to do all statistical analyses. A total of 8 studies were included for analysis. The combined results demonstrated that the pooled proportion of overall response rate (ORR) was 0.35 (95% CI 0.27 to 0.43, =0.000), and the pooled proportion of complete response rate (CRR) was 0.02 (95% CI 0.01 to 0.03, =0.541). Pomalidomide was generally well tolerated by patients reported in the studies. Further studies would be required to conduct more prospective randomized controlled trials (RCTs) with larger samples to assess the proper place of pomalidomide as single agent or combined with other agents for RRMM.
PubMed: 28819377
DOI: 10.7150/jca.17999 -
Journal of Clinical Medicine Aug 2020There is a paucity of head-to-head comparisons of the efficacy and harms of pharmacological treatments for systemic sclerosis-related interstitial lung disease (SSc-ILD). (Review)
Review
BACKGROUND
There is a paucity of head-to-head comparisons of the efficacy and harms of pharmacological treatments for systemic sclerosis-related interstitial lung disease (SSc-ILD).
METHODS
We conducted a network meta-analysis (NMA) in order to compare the effects of different treatments with the placebo on change in forced vital capacity (FVC), change in diffusion lung capacity for CO (DLCO), serious adverse events (SAEs), discontinuation for adverse events and mortality in SSc-ILD. Standardized mean difference (SMD) and log odds ratio were estimated using NMA with fixed effects.
RESULTS
Nine randomized clinical trials (926 participants) comparing eight interventions and the placebo for an average follow-up of one year were included. Compared to the placebo, only rituximab significantly reduced FVC decline (SMD (95% CI) = 1.00 (0.39 to 1.61)). Suitable data on FVC outcome for nintedanib were not available for the analysis. No treatments influenced DLCO. Safety and mortality were also not different across treatments and the placebo, although there were few reported events. Cyclophosphamide and pomalidomide were less tolerated than the placebo, mycophenolate, and nintedanib.
CONCLUSION
Only rituximab significantly reduced lung function decline compared to the placebo. However, direct head-to-head comparison studies are required to confirm these findings and to better determine the safety profile of various treatments.
PubMed: 32784580
DOI: 10.3390/jcm9082560 -
Clinical Lymphoma, Myeloma & Leukemia Jul 2019Pomalidomide (Pom) has demonstrated synergistic antiproliferative activity in combination regimens as a result of its distinct anticancer, antiangiogenic, and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Pomalidomide (Pom) has demonstrated synergistic antiproliferative activity in combination regimens as a result of its distinct anticancer, antiangiogenic, and immunomodulatory effects. This review aimed to compare outcome measures of different Pom regimens for relapsed/refractory multiple myeloma.
METHODS
A comprehensive literature search identified a total of 1374 studies. Thirty-five studies assessing 4623 subjects met the inclusion criteria: phase 2/3 trial, ≥ 2 prior lines of therapy, and clearly documented efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival. Statistical analyses for meta-analysis was performed by CMA version 3 and Cochrane Q statistics (P < .05 considered significant, I index for heterogeneity). A random effects model was used if there was significant heterogeneity (P ≥ .05 over I ≥ 50%).
RESULTS
Pooled analysis showed ORR 47.1% across all Pom-based (2- and 3-drug) regimens. Stratified analysis for efficacy outcomes (pooled ORR [%] and mean progression-free survival [months]) are reported. With doublet regimen, Pom with low-dose dexamethasone (LoDex) was the most common regimen (35.7%, 6.1 months), and overall survival was 14.37 months. With triplet regimens, pooled ORR was 61.9% (I = 87.3%). These included bortezomib + Pom + LoDex (83.5%, 15.7 months), carfilzomib-Pom + LoDex (77.1%, 15.3 months), Pom + LoDex-bendamustine (74.2%), Pom-dexamethasone-daratumumab (64.5%), Pom + LoDex-cyclophosphamide (59.4%, 9.5 months), and Pom + LoDex-doxorubicin (32%). Leading adverse events were myelosuppression, with mean incidences of grade 3 or higher neutropenia, anemia, and thrombocytopenia of 47.6%, 26.5%, and 20.8%, respectively. Mean incidence of grade 3 or higher nonhematologic adverse events were infections 29.1%, pneumonia 13.8%, and fatigue 10%.
CONCLUSION
Three-drug Pom regimens yielded double the response rates compared to Pom + LoDex (pooled ORR, 61.9% vs. 35.7%), with bortezomib + Pom + LoDex and carfilzomib-Pom + LoDex demonstrating better outcomes than other regimens.
Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Resistance, Neoplasm; Humans; Multiple Myeloma; Recurrence; Retreatment; Thalidomide; Treatment Outcome
PubMed: 31060991
DOI: 10.1016/j.clml.2019.04.003 -
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 -
Clinical Lymphoma, Myeloma & Leukemia Oct 2022Oral oncolytic treatments (OOTs) have improved the prognosis of patients with multiple myeloma (MM). However, the effectiveness of these therapies is undermined by poor... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Oral oncolytic treatments (OOTs) have improved the prognosis of patients with multiple myeloma (MM). However, the effectiveness of these therapies is undermined by poor adherence. We aimed to characterize the real-world adherence to, and persistence with, OOTs for MM.
MATERIALS AND METHODS
MEDLINE, EMBASE, and the International Pharmaceutical abstracts databases were searched for relevant observational studies published in English up to November 21, 2021. This was supplemented by manual searches of abstracts from the annual meetings of the American Society of Hematology, the American Society for Clinical Oncology, and the European Hematology Association as well as screening the references of included articles. Random-effects meta-analysis was performed.
RESULTS
Following screening of 11,557 articles, 19 studies involving 27,129 patients in 8 countries (France, the US, Germany, Italy, the UK, Brazil, South Korea, and Belgium) prescribed OOTs (lenalidomide, thalidomide, pomalidomide, panobinostat, ixazomib, and melphalan) for MM were included. The overall pooled proportion of adherent patients was 67.9% (95% confidence interval [CI]: 57.1%-77.8%). The pooled proportion of adherent patients was higher in self-reported questionnaire-based studies compared to those using prescription/dispensing data (81.6% vs. 61.0%; P-value for difference = .08). Across 5 studies involving 15,363 patients, a pooled proportion of 35.8% (95% CI: 22.0-50.9) discontinued treatment. Factors reported to be associated with nonadherence included increasing age, higher comorbidity, polypharmacy, and a lack of social support.
CONCLUSION
In patients with MM, adherence to and persistence with OOTs remains suboptimal. To achieve desired clinical outcomes, interventions to improve adherence and minimize discontinuation may be warranted.
Topics: Humans; Lenalidomide; Medication Adherence; Melphalan; Multiple Myeloma; Panobinostat; Pharmaceutical Preparations; Thalidomide
PubMed: 35764491
DOI: 10.1016/j.clml.2022.05.003 -
Annals of Hematology Mar 2021Multiple myeloma (MM) is an incurable disease, and patients usually receive multiple lines of therapy. Due to the abundance of novel treatments for MM, we conducted a... (Meta-Analysis)
Meta-Analysis
Multiple myeloma (MM) is an incurable disease, and patients usually receive multiple lines of therapy. Due to the abundance of novel treatments for MM, we conducted a network meta-analysis to identify combinations that could fare better than others in relapsed/refractory MM, in the setting of novel drugs. We searched PubMed and Cochrane databases for phase III trials in previously treated MM that had lenalidomide or bortezomib in the control arm. The primary endpoint was progression-free survival (PFS), extracted as hazard-ratio. We used the P score to rank treatments. Thirteen studies were included. All but two studies compared one novel agent against two, with or without dexamethasone. Based on the P score, daratumumab and pegylated liposomal doxorubicin had a higher probability of achieving better PFS, followed by isatuximab, carfilzomib, pomalidomide, and panobinostat. Although most overall survival data were not mature enough, the addition of a second or third novel agent to either immunomodulatory (IMID) or proteasome inhibitor (PI) backbone seemed to improve survival (HR = 0.84, 95CI 0.77-0.92). Severe adverse events were more frequent with isatuximab, panobinostat, and pomalidomide. In summary, in the absence of trials directly comparing two novel agents-based therapies, we provide a tool that indirectly compares these newer therapies and that can help physicians to prioritize some regimens over others.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Lenalidomide; Male; Middle Aged; Multiple Myeloma; Neoplasm Metastasis; Neoplasm Recurrence, Local; Network Meta-Analysis; Progression-Free Survival; Recurrence
PubMed: 33432438
DOI: 10.1007/s00277-021-04404-3 -
Clinical Lymphoma, Myeloma & Leukemia Jul 2021Lenalidomide use in nearly all induction regimens for multiple myeloma (MM) has led to the treatment of lenalidomide-refractory disease becoming one of the most...
INTRODUCTION
Lenalidomide use in nearly all induction regimens for multiple myeloma (MM) has led to the treatment of lenalidomide-refractory disease becoming one of the most important clinical questions in its treatment. Given the lack of direct comparisons of treatment regimens for lenalidomide-refractory MM, we used a systematic review to identify randomized controlled trials (RCTs) that included lenalidomide-refractory subgroup analysis.
METHODS
We performed a systematic review to identify RCTs for MM that enrolled patients with lenalidomide-refractory disease, then performed a network meta-analysis (NMA) using random effects model to compare regimens.
RESULTS
We identified 123 discrete RCTs, of which 7 reported primary outcomes for lenalidomide-refractory MM. These were linked in 2 discrete networks totaling 1698 lenalidomide-refractory patients. Network 1 compared bortezomib (bort)/dexamethasone (dex) versus other treatments, and analysis showed triplet therapy with pomalidomide (pom)/bort/dex (hazard ratios [HR] 0.65, 95% confidence interval [CI], 0.50-0.84), daratumumab (dara)/bort/dex (HR 0.36, 95% CI, 0.21-0.63), and dara/carfilzomib (carf)/dex (HR 0.38, 95% CI, 0.21-0.69) as more effective than bort/dex. Network 2 compared dex versus other treatments, and analysis showed pom/dex (HR 0.50, 95% CI, 0.40-0.62), isatuximab (isa)/pom/dex (HR 0.30, 95% CI, 0.20-0.44), and elotuzumab (elo)/pom/dex (HR 0.27, 95% CI, 0.16-0.45) as more effective than dex. Within each network, monoclonal antibody (mAb)-containing regimens had lower HRs and higher P-scores than non-mAb regimens, indicating higher likelihood of these regimens being most efficacious.
CONCLUSION
The results of our NMA demonstrated that for lenalidomide-refractory MM, triplet therapy containing mAbs are superior. There is need for further RCTs to better ascertain the best standard of care for these patients.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; Humans; Lenalidomide; Multiple Myeloma; Network Meta-Analysis; Progression-Free Survival; Randomized Controlled Trials as Topic
PubMed: 33962898
DOI: 10.1016/j.clml.2021.03.006