-
Skin Appendage Disorders Jan 2020Hair graying is a common sign of aging resulting from complex regulation of melanogenesis. Currently, there is no medical treatment available for hair repigmentation. In... (Review)
Review
Hair graying is a common sign of aging resulting from complex regulation of melanogenesis. Currently, there is no medical treatment available for hair repigmentation. In this article we review the literature on medication-induced hair repigmentation, discuss the potential mechanisms of action, and review the quality of the literary data. To date, there have been 27 studies discussing medication-induced gray hair repigmentation, including 6 articles on gray hair repigmentation as a primary objective, notably with psoralen treatment or vitamin supplementation, and 21 reports on medication-induced gray hair repigmentation as an incidental finding. Medications noted in the literature include anti-inflammatory medications (thalidomide, lenalidomide, adalimumab, acitretin, etretinate, prednisone, cyclosporin, cisplatinum, interferon-α, and psoralen), stimulators of melanogenesis (latanoprost, erlotinib, imatinib, tamoxifen, and levodopa), vitamins (calcium pantothenate and -amino benzoic acid), a medication that accumulates in tissues (clofazimine), and a medication with an undetermined mechanism (captopril). Diffuse repigmentation of gray hair can be induced by certain medications that inhibit inflammation or stimulate melanogenesis. There is also low-quality evidence that some vitamin B complex supplementation can promote gray hair darkening. While these compounds are not currently indicated for the treatment of gray hair, their mechanisms shed light on targets for future medications for hair repigmentation.
PubMed: 32021854
DOI: 10.1159/000504414 -
Advances in Therapy May 2022Many treatment regimens have been evaluated in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). The objective of this study was to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Many treatment regimens have been evaluated in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). The objective of this study was to compare the efficacy of relevant therapies for the treatment of TIE patients with NDMM.
METHODS
Progression-free survival (PFS) and overall survival (OS) from large randomised controlled trials (RCTs) evaluating different treatment options for TIE patients with NDMM were compared in a network meta-analysis (NMA). The NMA includes recent primary and long-term OS readouts from SWOG S0777, ENDURANCE, MAIA, and ALCYONE. Relevant trials were identified through a systematic literature review. Relative efficacy measures (i.e., hazard ratios [HRs] for PFS and OS) were extracted and synthesised in random-effects NMAs.
RESULTS
A total of 122 publications describing 45 unique RCTs was identified. Continuous lenalidomide/dexamethasone (Rd) was selected as the referent comparator. Daratumumab-containing treatments (daratumumab/lenalidomide/dexamethasone [D-Rd], daratumumab/bortezomib/melphalan/prednisone [D-VMP]) and bortezomib/lenalidomide/dexamethasone (VRd) had the highest probabilities of being more effective than Rd continuous for PFS (HR: D-Rd, 0.53; D-VMP, 0.57, VRd, 0.77) and OS (HR: D-Rd, 0.68; VRd, 0.77, D-VMP, 0.78). D-Rd had the highest chance of being ranked as the most effective treatment with respect to PFS and OS. Results using a smaller network focusing on only those regimens that are relevant in Europe were consistent with the primary analysis.
CONCLUSIONS
These comparative effectiveness data may help inform treatment selection in TIE patients with NDMM.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Humans; Lenalidomide; Multiple Myeloma; Network Meta-Analysis; Treatment Outcome
PubMed: 35246820
DOI: 10.1007/s12325-022-02083-8 -
Cancer Research and Treatment Jul 2023We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis. (Meta-Analysis)
Meta-Analysis
Efficacy of Salvage Treatments in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Including Chimeric Antigen Receptor T-Cell Therapy: A Systematic Review and Meta-Analysis.
PURPOSE
We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis.
MATERIALS AND METHODS
R/R DLBCL trials were divided into two groups based on eligibility for autologous stem-cell transplantation (ASCT), and meta-analysis of each group was performed. Random effects models were used to estimate the 1-year progression-free survival (PFS) rate, and chimeric antigen receptor (CAR) T-cell therapy was used as reference treatment.
RESULTS
Twenty-six ASCT-eligible cohorts from 17 studies comprising 2,924 patients and 59 ASCT-ineligible cohorts from 53 studies comprising 3,617 patients were included in the pooled analysis. In the ASCT-eligible group, the pooled 1-year PFS rate was 0.40 (95% confidence interval [CI], 0.15 to 0.65) for the CAR T-cell group and 0.34 (95% CI, 0.30 to 0.37) for the group with chemotherapy followed by ASCT intention. The two treatments were not significantly different in meta-regression analysis. In the ASCT-ineligible group, the pooled 1-year PFS was 0.40 (95% CI, 0.35 to 0.46) for CAR T-cell, and the highest primary outcome was 0.47 (95% CI, 0.37 to 0.57) for the tafasitamab group. CAR T-cell therapy showed significantly better outcomes than chemotherapy and therapies based on ibrutinib, lenalidomide, and selinexor. However, loncastuximab, polatuzumab plus bendamustine and rituximab, and the tafasitamab group showed no different efficacy than CAR T-cell therapy after adjusting for median number of previous lines of treatment.
CONCLUSION
Although several regimens were crudely grouped for classification, CAR T-cell therapy did not outperform chemotherapy followed by ASCT in the second-line setting or several recently developed agents in the ASCT-ineligible setting.
Topics: Humans; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Combined Modality Therapy; Antineoplastic Combined Chemotherapy Protocols; Salvage Therapy; Neoplasm Recurrence, Local; Hematopoietic Stem Cell Transplantation; Lymphoma, Large B-Cell, Diffuse
PubMed: 36915243
DOI: 10.4143/crt.2022.1658 -
PloS One 2013In recent years, a number of randomized controlled trials (RCTs) have reported on lenalidomide as a treatment for multiple myeloma (MM). Herein, we report results of a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In recent years, a number of randomized controlled trials (RCTs) have reported on lenalidomide as a treatment for multiple myeloma (MM). Herein, we report results of a meta-analysis of RCTs examining the efficacy and safety of lenalidomide for MM.
PATIENTS AND METHODS
Databases were searched using the terms "lenalidomide or revlimid AND multiple myeloma."RCTs evaluating initial or maintenance therapeutic outcomes were included. Main outcome measures were response rates, progression-free survival (PFS), overall survival, and adverse events.
RESULTS
Seven trials were included (N = 192-614 participants). Lenalidomide doses and treatment regimens differed between trials. Complete response (CR) and very good partial response (VGPR) risk ratios (RR) favored lenalidomide over placebo (CR = 2.54, 95% confidence interval [CI] = 1.29-5.02; VGPR = 2.82, 95% CI = 1.30-6.09). The PFS hazard ratio favored lenalidomide over placebo (0.37, 95% CI = 0.33-0.41). For adverse events, neutropenia, deep vein thrombosis (DVT), infection, and hematologic cancer RR favored placebo over lenalidomide (neutropenia: 4.74, 95% CI = 2.96-7.57; DVT: 2.52; 95% CI: 1.60-3.98; infection: 1.98; 95% CI: 1.50-2.62; hematologic cancer: 3.20; 95% CI: 1.28-7.98).
CONCLUSIONS
Lenalidomide is an effective treatment for MM; however, treatment-related adverse events must be considered and appropriate adjustments and/or prophylactic treatment should be initiated where possible.
Topics: Disease-Free Survival; Humans; Lenalidomide; Multiple Myeloma; Neoplasms, Second Primary; Randomized Controlled Trials as Topic; Thalidomide; Treatment Outcome
PubMed: 23691202
DOI: 10.1371/journal.pone.0064354 -
Oncotarget Jul 2017The immunomodulatory drug lenalidomide is highly effective against newly diagnosed and relapsed/refractory multiple myeloma (MM), but serious and even fatal infections... (Meta-Analysis)
Meta-Analysis Review
The immunomodulatory drug lenalidomide is highly effective against newly diagnosed and relapsed/refractory multiple myeloma (MM), but serious and even fatal infections have been associated with its use. In this meta-analysis, we assessed the overall risk of infection to MM patients treated with lenalidomide. Eleven phase II or III clinical trials, comprising 3,210 subjects, were selected from the Embase, Pubmed, and Cochrane Library databases, from the Clinical Trial Registration website, and from meeting abstracts and virtual presentations at the American Society of Clinical Oncology. Main outcome measures were overall incidence, relative risk (RR), and 95% confidence intervals (CIs) of reported infection events. Fixed-effect or random-effect models were used in the statistical analyses, depending on the between-study heterogeneity. The overall incidence of high-grade infection was 14.32% (95% CI: 12.08%-16.90%) and high-grade infection's pooled RR was 2.23 (95% CI: 1.71-2.91, P < 0.0001) for all 11 studies evaluated. No evidence of publication bias for the incidence of high-grade infection was detected using Begg's funnel plot and Egger's test (P = 0.2; 95% CI: -1.70, 1.23). From this meta-analysis, it appears lenalidomide use is associated with an increased risk of high-grade infection. Moreover, fatal infection events occurred only in patients treated with lenalidomide; no infection-related deaths were observed among controls. These data indicate that accurate diagnosis and optimal management of infection in MM patients treated with lenalidomide could be critical for treatment efficacy.
Topics: Antineoplastic Agents; Humans; Immunologic Factors; Incidence; Infections; Lenalidomide; Mortality; Multiple Myeloma; Publication Bias; Risk; Severity of Illness Index; Thalidomide
PubMed: 28423741
DOI: 10.18632/oncotarget.16235 -
Oncotarget May 2017Although two newly launched monoclonal antibodies (mAbs), elotuzumab and daratumumab, performed well in patients with relapsed or relapsed/refractory multiple myeloma... (Meta-Analysis)
Meta-Analysis Review
Although two newly launched monoclonal antibodies (mAbs), elotuzumab and daratumumab, performed well in patients with relapsed or relapsed/refractory multiple myeloma (RRMM), their efficacy and safety remain uncertain. We therefore performed a systematic review and meta-analysis of the most recent clinical trials that evaluated elotuzumab and/or daratumumab for the treatment of patients with RRMM. Our meta-analysis included 13 clinical trials with 2,402 patients participating. The overall response rate (ORR) was 57% (95% confidence interval [CI]: 38-76%), and the at least very good partial response rate (VGPR) was 32% (95% CI: 19-46%). mAb-based regimens prolonged progression-free survival (PFS, hazard ratio: 0.52, 95% CI: 0.36-0.75) compared to non-mAb-based regimens. Additionally, the efficacy of triplet regimens was superior to that of single or doublet regimens. The same trend was observed in a subgroup analysis of daratumumab and elotuzumab. The most common grade 3/4 adverse events included neutropenia, lymphopenia, thrombocytopenia, anemia, leukopenia, pneumonia, and fatigue. Elotuzumab and daratumumab improved the ORR, at least VGPR, and PFS compared to non-mAb-based regimens. In a pooled analysis, both mAbs had promising efficacy and safety profiles, particularly in triplet regimens. The same trend was observed in daratumumab- and elotuzumab-based regimens. Daratumumab triplet therapy (daratumumab, lenalidomide, and dexamethasone) was superior to other triplet regimens for the treatment of RRMM, and daratumumab monotherapy was more effective than either single agent in heavily pretreated MM patients, suggesting CD38 is an effective target for treatment of RRMM. Additional clinical studies of elotuzumab and daratumumab will be required to validate these results.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Drug Resistance, Neoplasm; Humans; Multiple Myeloma; Odds Ratio; Recurrence; Treatment Outcome
PubMed: 28454113
DOI: 10.18632/oncotarget.16987 -
Oncology Letters Sep 2017The present review aimed to assess the safety and efficacy of thalidomide and lenalidomide, two immunomodulatory drugs with anti-angiogenic properties, in women with...
The present review aimed to assess the safety and efficacy of thalidomide and lenalidomide, two immunomodulatory drugs with anti-angiogenic properties, in women with recurrent ovarian, fallopian tube, and primary peritoneal cancer. A systematic review of the literature was conducted whereby Medline and the Cochrane Central Register of Controlled Trials were searched using terms associated with thalidomide, lenalidomide, and recurrent ovarian, fallopian tube and primary peritoneal cancer. Published English language case reports, trials and studies that described the safety and efficacy of thalidomide or lenalidomide alone, or in combination with other drugs were reviewed. A total of 16 clinical studies involving 394 patients treated with thalidomide (n=188), lenalidomide (n=77) and 129 controls were identified, including five case reports (n=6), three case series (n=45), two phase I trials (n=27), four phase II trials (n=109), and two randomized phase III trials (n=207). In a pooled analysis of thalidomide investigated as a single drug, the overall clinical benefit rate was 43% (43/99) with a mean time to progression of 5.6 months. The response rate (complete response + partial response) was 25%. In a phase III trial, the combination of thalidomide and topotecan significantly increased the overall response rate compared with topotecan alone [14/30 (47%) vs. 8/39 (21%)]. In another phase III trial involving women with asymptomatic biochemical recurrence, compared with tamoxifen, thalidomide was not more effective. Lenalidomide was investigated in three phase I trials and in one phase II trial with an overall clinical benefit rate of 52% (34/65), and a mean time to progression of 4.6 months. The response rate (complete response + partial response) was 6%. Systemic toxicity of both drugs was noted in >77% of patients with pneumonitis/pneumonia, fatigue, neuropathy and venous thromboembolism reported as the most common side effects. Thalidomide and lenalidomide are moderately active in recurrent ovarian cancer. Thalidomide possesses synergistic effects with topotecan. The toxicity of both drugs is considerable and there is a greater amount of data available for thalidomide compared to lenalidomide.
PubMed: 28927084
DOI: 10.3892/ol.2017.6578 -
PloS One 2016Lenalidomide could effectively induce red blood cell (RBC) transfusion independence (TI) in patients with lower-risk (Low/Intermediate-1) myelodysplastic syndrome (MDS)... (Meta-Analysis)
Meta-Analysis Review
Efficacy and Safety of Lenalidomide for Treatment of Low-/Intermediate-1-Risk Myelodysplastic Syndromes with or without 5q Deletion: A Systematic Review and Meta-Analysis.
BACKGROUND
Lenalidomide could effectively induce red blood cell (RBC) transfusion independence (TI) in patients with lower-risk (Low/Intermediate-1) myelodysplastic syndrome (MDS) with or without 5q deletion. However whether lenalidomide ultimately improves the overall survival (OS) of lower-risk MDS patients and reduces the progression to AML remains controversial.
METHOD
A meta-analysis was conducted to examine the efficacy and safety of lenalidomide in the treatment of lower-risk MDS. Efficacy was assessed according to erythroid hematologic response (HI-E), cytogenetic response (CyR), OS and AML progression. Safety was evaluated based on the occurrence rates of grades 3-4 adverse events (AEs).
RESULTS
Seventeen studies were included consisting of a total of 2160 patients. The analysis indicated that the overall rate of HI-E was 58% with 95% confidence interval (CI) of 43-74%. The pooled estimates for the rates of CyR, complete CyR, and partial CyR were 44% (95% CI 19-68%), 21% (95% CI 13-30%) and 23% (95% CI 15-32%), respectively. The patients with 5q deletion had significantly higher rate of HI-E and CyR than those without 5q deletion (P = 0.002 and 0.001, respectively). The incidences of grades 3-4 neutropenia, thrombocytopenia, leukopenia, anemia, deep vein thrombosis, diarrhea, fatigue and rash were 51% (95% CI 30-73%), 31% (95% CI 20-42%), 9% (95% CI 5-13%), 7% (95% CI 2-12%), 3% (95% CI 2-5%), 3% (95% CI 1-5%), 2% (95% CI 1-4%) and 2% (95% CI 1-3%), respectively. Lenalidomide significantly improved OS (HR: 0.62, 95% CI 0.47-0.83, P = 0.001) and lowered the risk of AML progression in del(5q) patients (RR: 0.61, 95% CI 0.41-0.91, P = 0.014).
CONCLUSIONS
In spite of the AEs, lenalidomide could be effectively and safely used for the treatment of lower-risk MDS patients with or without 5q deletion.
Topics: Anemia, Macrocytic; Chromosome Deletion; Chromosomes, Human, Pair 5; Humans; Immunologic Factors; Lenalidomide; Myelodysplastic Syndromes; Thalidomide; Treatment Outcome
PubMed: 27824902
DOI: 10.1371/journal.pone.0165948 -
Frontiers in Oncology 2021Several maintenance therapies are available for treatment of patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). The objective of this review...
INTRODUCTION
Several maintenance therapies are available for treatment of patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). The objective of this review was to assess the efficacy and safety of lenalidomide monotherapy in these patients.
METHODS
MEDLINE, EMBASE, and the Cochrane Library databases were searched for publications up to April 7, 2021. Original studies that had information on lenalidomide monotherapy for DLBCL patients with R/R status were included. Meta-analyses of response rates, adverse events (AEs), overall survival (OS), and progression-free survival (PFS) were performed. The pooled event rates were calculated using a double arcsine transformation to stabilize the variances of the original proportions. Subgroup analysis was used to compare patients with different germinal center B-cell-like (GCB) phenotypes.
RESULTS
We included 11 publications that examined DLBCL patients with R/R status. These studies were published from 2008 to 2020. The cumulative objective response rate (ORR) for lenalidomide monotherapy was 0.33 (95% CI: 0.26, 0.40), and the ORR was better in patients with the non-GCB phenotype (0.50; 95% CI: 0.26, 0.74) than the GCB phenotype (0.06; 95% CI: 0.03, 0.11). The major serious treatment-related AEs were neutropenia, thrombocytopenia, respiratory disorders, anemia, and diarrhea. The median PFS ranged from 2.6 to 34 months and the median OS ranged from 7.8 to 37 months.
CONCLUSION
This study provides evidence that lenalidomide monotherapy was active and tolerable in DLBCL patients with R/R status. Patients in the non-GCB subgroup had better responsiveness.
PubMed: 34926259
DOI: 10.3389/fonc.2021.756728 -
Journal of Hematology Aug 2022Light chain deposition disease (LCDD) is a rare hematologic disorder that can affect any organ but predominantly involves the kidneys. Existing literature is limited to... (Review)
Review
Light chain deposition disease (LCDD) is a rare hematologic disorder that can affect any organ but predominantly involves the kidneys. Existing literature is limited to case reports and small single-center retrospective series, explaining the lack of any treatment algorithms and management guidelines for patients with this disorder. In this systematic review of literature, we explored the role of standard and high-dose chemotherapy-autologous stem cell transplant for LCDD. A total of 11 studies were identified to evaluate the hematologic and renal responses to various treatment regimens. Autologous stem cell transplant and bortezomib-based regimens appear to have reasonable safety and efficacy for this rare hematologic disorder, albeit some statistical and analytical limitations. Large multicenter retrospective and prospective studies are needed to better elucidate the role of various chemotherapy regimens as well as autologous stem cell transplant for patients with LCDD.
PubMed: 36118549
DOI: 10.14740/jh1038