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American Journal of Hematology Sep 2018
Topics: Analgesics, Opioid; Animals; Anticonvulsants; Cyclin-Dependent Kinases; Drug-Related Side Effects and Adverse Reactions; Humans; Immunoglobulins, Intravenous; Proteasome Inhibitors; Thrombotic Microangiopathies
PubMed: 29985540
DOI: 10.1002/ajh.25208 -
OncoTargets and Therapy 2019To evaluate the efficacy and safety of rituximab-based combination therapy for Waldenström macroglobulinemia (WM), we conducted this meta-analysis by pooling the rates...
BACKGROUND
To evaluate the efficacy and safety of rituximab-based combination therapy for Waldenström macroglobulinemia (WM), we conducted this meta-analysis by pooling the rates of overall response, major response, complete response, and grade ≥3 hematological adverse events.
METHODS AND MATERIALS
We searched for relevant studies in the databases of PubMed, Web of Science, Embase, and the Cochrane Library. The qualitative assessment of all the included articles was conducted with reference to the Newcastle-Ottawa Scale. A random-effects model was selected to perform all pooled analyses.
RESULTS
We identified altogether 22 studies with a total of 806 symptomatic WM patients enrolled. The pooled analysis indicated that the rituximab-based combination therapy achieved an overall response rate (ORR) of 84% (95% CI: 81%-87%), a major response rate (MRR) of 71% (95% CI: 66%-75%), and a complete response rate (CRR) of 7% (95% CI: 5%-10%). Rituximab plus conventional alkylating agents-containing chemotherapy (subgroup A) yielded an ORR of 86% (95% CI: 81%-89%), an MRR of 74% (95% CI: 69%-79%), and a CRR of 8% (95% CI: 4%-14%). Rituximab plus purine analog (subgroup B) resulted in an ORR of 85% (95% CI: 79%-89%), an MRR of 74% (95% CI: 66%-81%), and a CRR of 9% (95% CI: 4%-15%). Rituximab plus proteasome inhibitor (subgroup C) resulted in an ORR of 86% (95% CI: 81%-90%), an MRR of 68% (95% CI: 58%-77%), and a CRR of 7% (95% CI: 3%-11%). Rituximab plus immunomodulatory drug (subgroup D) attained relatively lower response rates, with an ORR of 67% (95% CI: 51%-81%), an MRR of 56% (95% CI: 27%-83%), and a CRR of 5% (95% CI: 1%-12%). Common grade ≥3 hematological adverse events consisted of neutropenia (33%, 95% CI: 17%-52%), thrombocytopenia (7%, 95% CI: 3%-11%), and anemia (5%, 95% CI: 3%-9%).
CONCLUSION
Rituximab in combination with an alkylating agent, purine analog, or proteasome inhibitor is highly effective with tolerable hematological toxicities for WM.
PubMed: 31043792
DOI: 10.2147/OTT.S191179 -
Clinical Therapeutics Mar 2018New therapies, including daratumumab plus lenalidomide plus dexamethasone (DRd) and daratumumab plus bortezomib plus dexamethasone (DVd), have recently been approved in... (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
New therapies, including daratumumab plus lenalidomide plus dexamethasone (DRd) and daratumumab plus bortezomib plus dexamethasone (DVd), have recently been approved in the United States for patients with multiple myeloma (MM) who have received at least 1 prior line of therapy. However, few treatments have been compared in head-to-head clinical trials to determine the most efficacious therapy. In an update of the POLLUX (Phase 3 Study Comparing DRd Versus Rd in Subjects with Relapsed or Refractory Multiple Myeloma [RRMM]) trial, median progression-free survival (PFS) for DRd was not reached; the hazard ratio compared with Rd was 0.41. In an update of the CASTOR (Phase 3 Study Comparing DVd Versus Vd in Subjects with RRMM) trial, median PFS for DVd was 16.7 months, compared with 7.1 months for Vd with a PFS hazard ratio of 0.31. A systematic literature review and network meta-analysis (NMA) was performed to estimate the relative efficacy of treatments for previously treated patients with MM.
METHODS
A systematic search of MEDLINE, EMBASE, BioSciences Information Service, and the Cochrane Library databases was conducted from initiation to September 2016. Abstracts published by international congresses (2014-2016) and bibliographies of pertinent systematic reviews and meta-analyses were also searched. Eligible studies consisted of randomized controlled trials (RCTs) or long-term follow-up studies with >1 treatment arm assessing the efficacy or safety of MM therapies. An NMA was conducted by using Bayesian fixed effect mixed-treatment comparisons. Outcomes considered were hazard ratios for PFS and odds ratios for overall response rate (ORR).
FINDINGS
In total, 108 articles reporting 27 RCTs were included in the NMA. Data formed 2 evidence networks: RCTs with DRd and RCTs with DVd. Primary analysis of PFS found that DRd and DVd had a higher probability of being the best treatments (probability, 0.997 and 0.999, respectively) and had the lowest risk of progression or death than other treatments approved by the US Food and Drug Administration for the treatment of MM. Results from sensitivity analyses using time to progression as a proxy for missing PFS data were consistent. DRd and DVd also showed improved ORR compared with other treatments. Subgroup analyses of PFS in patients treated with only 1 prior therapy were like the results of the primary analyses.
IMPLICATIONS
This NMA provides comparative efficacy for MM treatments not studied in head-to-head RCTs. The NMA suggests that, compared with other approved MM treatments in the United States, DRd and DVd have a higher probability of providing the longest PFS in patients who have received at least 1 prior therapy and in patients who have received only 1 prior therapy.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Bortezomib; Dexamethasone; Humans; Lenalidomide; Multiple Myeloma; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 29500140
DOI: 10.1016/j.clinthera.2018.01.014 -
BMC Cancer Jun 2021Patients with multiple myeloma (MM) remain at an increased risk of infection due to the disease process, as well as the ensuing treatments. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with multiple myeloma (MM) remain at an increased risk of infection due to the disease process, as well as the ensuing treatments.
METHODS
We performed a systematic review to evaluate the monthly risk of grade III/IV infection, pneumonia, and neutropenia in patients with myeloma enrolled in randomized clinical trials (RCTs).
RESULTS
The risk of grade III or higher infection, pneumonia, and neutropenia persists among all phases of treatment. There was no statistical difference in grade III or higher infection, pneumonia, and neutropenia between frontline and relapsed/refractory setting. In the maintenance setting, the complications of infection, pneumonia, and neutropenia were low, but not negligible. Three-drug regimens were no more likely than two-drug regimens to have an increased risk of Grade III or higher infection.
CONCLUSIONS
This is the first study to quantify the monthly risk of grade III or higher infection, pneumonia, and neutropenia across different treatment regimens in the frontline, maintenance, and relapsed/refractory settings. The results of our systematic review demonstrate a significant risk for severe infection, pneumonia, and neutropenia in patients with MM. Further studies are needed to determine the value of antibiotic prophylaxis in a broader myeloma patient population, as well as other approaches that will further mitigate the morbidity and mortality related to infection in this vulnerable patient population.
Topics: History, 21st Century; Humans; Infections; Multiple Myeloma; Risk Factors
PubMed: 34172037
DOI: 10.1186/s12885-021-08451-x -
British Journal of Haematology Jul 2020
Meta-Analysis
Topics: Aged; Humans; Middle Aged; Multiple Myeloma; Oligopeptides; Proteasome Inhibitors; Randomized Controlled Trials as Topic
PubMed: 32400886
DOI: 10.1111/bjh.16735 -
Cancer Apr 2020Thromboprophylaxis is routinely used with lenalidomide-based regimens in multiple myeloma because of a substantial risk of venous thromboembolism (VTE). However, little... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thromboprophylaxis is routinely used with lenalidomide-based regimens in multiple myeloma because of a substantial risk of venous thromboembolism (VTE). However, little is known about the incidence of VTE with contemporary lenalidomide-based regimens. The objective of the current study was to estimate the incidence of VTE despite thromboprophylaxis with currently used lenalidomide-based regimens in patients with myeloma.
METHODS
The Ovid MEDLINE, Embase, and Cochrane databases were queried from study inception to January 2019 for keywords to cover the following concepts: "lenalidomide," "venous thromboembolism," and "multiple myeloma." Phase 1, 2, and 3 clinical trials evaluating lenalidomide-based regimens with thromboprophylaxis were included. The pooled incidence rate of VTE was estimated using a random-effects model.
RESULTS
The search generated 1372 citations, with 51 clinical trials and 9069 patients included for analysis. The most common thromboprophylaxis agents were aspirin, low-molecular-weight heparin or warfarin, administered either per risk-stratification or at investigators' discretion. The pooled incidence of VTE in trials of patients who had newly diagnosed and relapsed/refractory myeloma was 6.2% (95% CI, 5.4%-7.1%) over median treatment durations ranging from 2 to 34 cycles, which translated into 1.2 VTE events per 100 patient-cycles (95% CI, 0.9-1.7 VTE events per 100 patient-cycles). Among contemporary regimens, the risk of VTE was low with combined lenalidomide and low-dose dexamethasone (0.2 [95% CI, 0.1-0.6] events/100 patient-cycles) and lenalidomide maintenance (0.0 [95% CI, 0.0-0.7] events per 100 patient-cycles). VTE risk was higher with combined lenalidomide and low-dose dexamethasone plus proteasome inhibitors (1.3 [95% CI, 0.7-2.3] events per 100 patient-cycles).
CONCLUSIONS
Despite adequate thromboprophylaxis, lenalidomide-based regimens have a substantial risk of VTE in controlled clinical trial settings. Further studies are needed on new thromboprophylaxis strategies with regimens that have a high VTE risk.
Topics: Angiogenesis Inhibitors; Anticoagulants; Dexamethasone; Humans; Incidence; Lenalidomide; Multiple Myeloma; Venous Thromboembolism
PubMed: 31913498
DOI: 10.1002/cncr.32682 -
Pharmacology Research & Perspectives Aug 2021Daratumumab was approved in patients with relapsed or refractory multiple myeloma (MM) who previously received proteasome inhibitors or immunomodulatory drugs. However,... (Meta-Analysis)
Meta-Analysis
Daratumumab was approved in patients with relapsed or refractory multiple myeloma (MM) who previously received proteasome inhibitors or immunomodulatory drugs. However, the efficacy and safety of the addition of daratumumab in subpopulations of patients with relapsed or refractory MM is still unknown. We systematically searched MEDLINE, EMBASE, and Cochrane for randomized controlled trials (inception to September 2020). All phase 3 randomized controlled trials (RCTs) which were conducted in patients with relapsed or refractory MM and compared the efficacy or safety with the addition of daratumumab versus control were adopted. Three studies including 1497 patients met our criteria. The addition of daratumumab increased the rates of overall response (RR 1.21, 95% CI 1.15-1.28, p < .001), complete response or better (RR 2.43, 95% CI 2.00-2.96, p < .001), very good partial response or better (RR 1.63, 95% CI 1.48-1.80, p < .001) compared with those with control. No clear evidence of heterogeneity was found in comparisons of progression-free survival obtained from subsets of studies grouped by the age of participant, ISS disease stage, type of measurable MM, the level of baseline renal function, cytogenetic profile. The results showed progression-free survival benefit was consistent between the treatment groups regarding previous clinical therapy information. Patients receiving daratumumab had higher risks of lymphopenia and infusion-related reactions of any grade and grade 3 or 4. In conclusions, this study provides a clear proof of beneficial effects of daratumumab-based therapy in patients with relapsed or refractory MM with an acceptable safety profile. The progression-free survival benefit was consistent regardless of patient's baseline characteristics or previous therapy agents.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Drug Resistance, Neoplasm; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Recurrence
PubMed: 34128350
DOI: 10.1002/prp2.797