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BMC Endocrine Disorders Jan 2022Adipocytes and their products, adipocytokines, play important roles in the generation and development of multiple myeloma (MM). Studies have demonstrated some... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adipocytes and their products, adipocytokines, play important roles in the generation and development of multiple myeloma (MM). Studies have demonstrated some adipocytokines to be associated with MM, although those results are controversial. Therefore, we conducted a meta-analysis to verify the association of adipocytokines with MM.
METHODS
We performed a systematic retrieval of literature published prior to 26 October 2021. Standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated to evaluate pooled effects. Subgroup analysis and meta-regression analysis were conducted to detect sources of heterogeneity. Sensitivity analysis was performed to evaluate the stability of the study. Publication bias was assessed by funnel plots and Egger's linear regression test.
RESULTS
Ten eligible studies with 1269 MM patients and 2158 controls were included. The pooled analyses indicated that circulating leptin levels of MM patients were significantly higher than control levels (SMD= 0.87, 95%CI: 0.33 to 1.41), while the circulating adiponectin levels in MM patients were significantly lower than controls with a pooled SMD of -0.49 (95%CI: -0.78 to -0.20). The difference of circulating resistin levels were not significant between MM patients and controls (SMD= -0.08, 95%CI: -0.55 to 0.39). Subgroup analysis and meta-regression analysis found that sample size, age, and sex were possible sources of heterogeneity. Sensitivity analysis demonstrated our pooled results to be stable.
CONCLUSION
Decreased circulating adiponectin and increased leptin levels were associated with the occurrence and development of MM. Adiponectin and leptin may be potential biomarkers and therapeutic targets for MM.
Topics: Adipokines; Biomarkers, Tumor; Case-Control Studies; Humans; Multiple Myeloma
PubMed: 35073877
DOI: 10.1186/s12902-022-00939-2 -
Scientific Reports Nov 2021Daratumumab has shown clinical benefit in multiple myeloma. We aimed to evaluate the safety and efficacy of adding daratumumab to backbone anti-myeloma treatments.... (Meta-Analysis)
Meta-Analysis
Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials.
Daratumumab has shown clinical benefit in multiple myeloma. We aimed to evaluate the safety and efficacy of adding daratumumab to backbone anti-myeloma treatments. Systematic search was performed up to August 2021 to identify randomised controlled trials comparing the outcomes of backbone therapy with and without daratumumab in relapsed/refractory and newly diagnosed myeloma (RRMM and NDMM, respectively). Odds ratios (ORs) and hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). Primary outcomes were death or disease progression, minimal residual disease (MRD) negativity, and stringent complete response (sCR). Secondary outcomes were complete response or better and safety endpoints prespecified in the study protocol: PROSPERO (CRD42020222904). In NDMM, MRD negativity [OR = 3.61 (CI 2.33-5.61)] and sCR [OR = 2.29 (CI 1.49-3.51)] were more likely and death or disease progression [HR = 0.47 (CI 0.39-0.57)] was less likely to occur with daratumumab compared to control. Regarding RRMM, MRD negativity [OR = 5.43 (CI 2.76-10.66)] and sCR [OR = 3.08 (CI 2.00-4.76)] were more likely and death or disease progression was less likely [HR = 0.50 (CI 0.37-0.67)] with daratumumab compared to control. The addition of daratumumab has shown high clinical efficacy and acceptable toxicity profile for the treatment of NDMM and RRMM regarding the endpoints examined.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Disease Progression; Humans; Multiple Myeloma; Progression-Free Survival; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34754015
DOI: 10.1038/s41598-021-01440-x -
The Cochrane Database of Systematic... Sep 2021Multiple myeloma is a malignant plasma cell disorder characterised by clonal plasma cells that cause end-organ damage such as renal failure, lytic bone lesions,... (Review)
Review
BACKGROUND
Multiple myeloma is a malignant plasma cell disorder characterised by clonal plasma cells that cause end-organ damage such as renal failure, lytic bone lesions, hypercalcaemia and/or anaemia. People with multiple myeloma are treated with immunomodulatory agents including lenalidomide, pomalidomide, and thalidomide. Multiple myeloma is associated with an increased risk of thromboembolism, which appears to be further increased in people receiving immunomodulatory agents.
OBJECTIVES
(1) To systematically review the evidence for the relative efficacy and safety of aspirin, oral anticoagulants, or parenteral anticoagulants in ambulatory patients with multiple myeloma receiving immunomodulatory agents who otherwise have no standard therapeutic or prophylactic indication for anticoagulation. (2) To maintain this review as a living systematic review by continually running the searches and incorporating newly identified studies.
SEARCH METHODS
We conducted a comprehensive literature search that included (1) a major electronic search (14 June 2021) of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE via Ovid, and Embase via Ovid; (2) hand-searching of conference proceedings; (3) checking of reference lists of included studies; and (4) a search for ongoing studies in trial registries. As part of the living systematic review approach, we are running continual searches, and we will incorporate new evidence rapidly after it is identified.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing the benefits and harms of oral anticoagulants such as vitamin K antagonist (VKA) and direct oral anticoagulants (DOAC), anti-platelet agents such as aspirin (ASA), and parenteral anticoagulants such as low molecular weight heparin (LMWH)in ambulatory patients with multiple myeloma receiving immunomodulatory agents.
DATA COLLECTION AND ANALYSIS
Using a standardised form, we extracted data in duplicate on study design, participants, interventions, outcomes of interest, and risk of bias. Outcomes of interest included all-cause mortality, symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, and minor bleeding. For each outcome we calculated the risk ratio (RR) with its 95% confidence interval (CI) and the risk difference (RD) with its 95% CI. We then assessed the certainty of evidence at the outcome level following the GRADE approach (GRADE Handbook).
MAIN RESULTS
We identified 1015 identified citations and included 11 articles reporting four RCTs that enrolled 1042 participants. The included studies made the following comparisons: ASA versus VKA (one study); ASA versus LMWH (two studies); VKA versus LMWH (one study); and ASA versus DOAC (two studies, one of which was an abstract). ASA versus VKA One RCT compared ASA to VKA at six months follow-up. The data did not confirm or exclude a beneficial or detrimental effect of ASA relative to VKA on all-cause mortality (RR 3.00, 95% CI 0.12 to 73.24; RD 2 more per 1000, 95% CI 1 fewer to 72 more; very low-certainty evidence); symptomatic DVT (RR 0.57, 95% CI 0.24 to 1.33; RD 27 fewer per 1000, 95% CI 48 fewer to 21 more; very low-certainty evidence); PE (RR 1.00, 95% CI 0.25 to 3.95; RD 0 fewer per 1000, 95% CI 14 fewer to 54 more; very low-certainty evidence); major bleeding (RR 7.00, 95% CI 0.36 to 134.72; RD 6 more per 1000, 95% CI 1 fewer to 134 more; very low-certainty evidence); and minor bleeding (RR 6.00, 95% CI 0.73 to 49.43; RD 23 more per 1000, 95% CI 1 fewer to 220 more; very low-certainty evidence). One RCT compared ASA to VKA at two years follow-up. The data did not confirm or exclude a beneficial or detrimental effect of ASA relative to VKA on all-cause mortality (RR 0.50, 95% CI 0.05 to 5.47; RD 5 fewer per 1000, 95% CI 9 fewer to 41 more; very low-certainty evidence); symptomatic DVT (RR 0.71, 95% CI 0.35 to 1.44; RD 22 fewer per 1000, 95% CI 50 fewer to 34 more; very low-certainty evidence); and PE (RR 1.00, 95% CI 0.25 to 3.95; RD 0 fewer per 1000, 95% CI 14 fewer to 54 more; very low-certainty evidence). ASA versus LMWH Two RCTs compared ASA to LMWH at six months follow-up. The pooled data did not confirm or exclude a beneficial or detrimental effect of ASA relative to LMWH on all-cause mortality (RR 1.00, 95% CI 0.06 to 15.81; RD 0 fewer per 1000, 95% CI 2 fewer to 38 more; very low-certainty evidence); symptomatic DVT (RR 1.23, 95% CI 0.49 to 3.08; RD 5 more per 1000, 95% CI 11 fewer to 43 more; very low-certainty evidence); PE (RR 7.71, 95% CI 0.97 to 61.44; RD 7 more per 1000, 95% CI 0 fewer to 60 more; very low-certainty evidence); major bleeding (RR 6.97, 95% CI 0.36 to 134.11; RD 6 more per 1000, 95% CI 1 fewer to 133 more; very low-certainty evidence); and minor bleeding (RR 1.42, 95% CI 0.35 to 5.78; RD 4 more per 1000, 95% CI 7 fewer to 50 more; very low-certainty evidence). One RCT compared ASA to LMWH at two years follow-up. The pooled data did not confirm or exclude a beneficial or detrimental effect of ASA relative to LMWH on all-cause mortality (RR 1.00, 95% CI 0.06 to 15.89; RD 0 fewer per 1000, 95% CI 4 fewer to 68 more; very low-certainty evidence); symptomatic DVT (RR 1.20, 95% CI 0.53 to 2.72; RD 9 more per 1000, 95% CI 21 fewer to 78 more; very low-certainty evidence); and PE (RR 9.00, 95% CI 0.49 to 166.17; RD 8 more per 1000, 95% CI 1 fewer to 165 more; very low-certainty evidence). VKA versus LMWH One RCT compared VKA to LMWH at six months follow-up. The data did not confirm or exclude a beneficial or detrimental effect of VKA relative to LMWH on all-cause mortality (RR 0.33, 95% CI 0.01 to 8.10; RD 3 fewer per 1000, 95% CI 5 fewer to 32 more; very low-certainty evidence); symptomatic DVT (RR 2.32, 95% CI 0.91 to 5.93; RD 36 more per 1000, 95% CI 2 fewer to 135 more; very low-certainty evidence); PE (RR 8.96, 95% CI 0.49 to 165.42; RD 8 more per 1000, 95% CI 1 fewer to 164 more; very low-certainty evidence); and minor bleeding (RR 0.33, 95% CI 0.03 to 3.17; RD 9 fewer per 1000, 95% CI 13 fewer to 30 more; very low-certainty evidence). The study reported that no major bleeding occurred in either arm. One RCT compared VKA to LMWH at two years follow-up. The data did not confirm or exclude a beneficial or detrimental effect of VKA relative to LMWH on all-cause mortality (RR 2.00, 95% CI 0.18 to 21.90; RD 5 more per 1000, 95% CI 4 fewer to 95 more; very low-certainty evidence); symptomatic DVT (RR 1.70, 95% CI 0.80 to 3.63; RD 32 more per 1000, 95% CI 9 fewer to 120 more; very low-certainty evidence); and PE (RR 9.00, 95% CI 0.49 to 166.17; RD 8 more per 1000, 95% CI 1 fewer to 165 more; very low-certainty evidence). ASA versus DOAC One RCT compared ASA to DOAC at six months follow-up. The data did not confirm or exclude a beneficial or detrimental effect of ASA relative to DOAC on DVT, PE, and major bleeding and minor bleeding (minor bleeding: RR 5.00, 95% CI 0.31 to 79.94; RD 4 more per 1000, 95% CI 1 fewer to 79 more; very low-certainty evidence). The study reported that no DVT, PE, or major bleeding events occurred in either arm. These results did not change in a meta-analysis including the study published as an abstract.
AUTHORS' CONCLUSIONS
The certainty of the available evidence for the comparative effects of ASA, VKA, LMWH, and DOAC on all-cause mortality, DVT, PE, or bleeding was either low or very low. People with multiple myeloma considering antithrombotic agents should balance the possible benefits of reduced thromboembolic complications with the possible harms and burden of anticoagulants. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
Topics: Anticoagulants; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Multiple Myeloma
PubMed: 34582035
DOI: 10.1002/14651858.CD014739 -
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 -
Annals of Palliative Medicine Jul 2021There has been long-standing controversy regarding the effectiveness and safety of lenalidomide as a maintenance treatment for patients with multiple myeloma (MM) after... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of lenalidomide in the treatment of multiple myeloma patients after allo-hematopoietic stem-cell transplantation: a systematic review and meta-analysis.
BACKGROUND
There has been long-standing controversy regarding the effectiveness and safety of lenalidomide as a maintenance treatment for patients with multiple myeloma (MM) after allogeneic cell transplantation. This meta-analysis aimed to explore the effectiveness and safety of lenalidomide in the maintenance treatment of MM patients after allogeneic cell transplantation based on published data.
METHODS
A systematic review and meta-analysis was conducted in English and Chinese databases, covering all available publications until 1 December 2020. Statistical analysis was performed using the software STATA 14.0, and odds ratios (ORs) combined with 95% confidence intervals (CIs) were calculated to explore the efficacy and safety of lenalidomide in the treatment of MM patients after allogeneic cell transplantation.
RESULTS
A total of 173 MM cases in 8 independent studies from 2007 to 2014 were included. Through a single-arm meta-analysis of the disease status of MM patients after lenalidomide treatment, 3.6% of patients were in minimal response (MR, P=0.006), 39.0% were in complete remission (CR, P=0.169), 20.2% in partial remission (PR, P<0.001), 12.8% in very good partial remission (VGPR, P=0.049), and 9.7% in SD (P=0.023); the PD was 5.6% (P=0.010). Through meta-analysis of adverse reactions after taking lenalidomide, 35.3% (P=0.628) of participants developed acute graft-versus-host disease (GVHD); 22.6% (P=0.049) developed chronic GVHD; 20.3% (P=0.001) developed infection; 22.5% (P=0.352) had thrombocytopenia; 32.5% (P<0.000) had neutropenia; pain occurred in 17.8% (P=0.350) of patients, and peripheral neuropathy occurred in 17.8% (P=0.995) of participants. The overall survival (OS) of ≥2 years and progression-free survival (PFS) of ≥2 years of MM patients after allo-hematopoietic-stem-cell transplantation (HSCT) taking lenalidomide were analyzed, and the results were 64.9% (P=0.049) and 58.4% (P=0.890), respectively.
DISCUSSION
Lenalidomide is effective in the treatment of MM patients after allo-HSCT, and reducing the incidence of infection and peripheral neuropathy, but it is not effective in reducing GVHD and blood system adverse reactions.
Topics: Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Lenalidomide; Multiple Myeloma; Transplantation, Homologous; Treatment Outcome
PubMed: 34353061
DOI: 10.21037/apm-21-1598 -
PloS One 2021Immunoproliferative Small Intestinal Disease (IPSID) is a disease characterized by extra-nodal marginal zone B-cell lymphoma with villous atrophy in the small intestine,...
Immunoproliferative Small Intestinal Disease (IPSID) is a disease characterized by extra-nodal marginal zone B-cell lymphoma with villous atrophy in the small intestine, causing chronic intermittent non-bloody diarrhea. Although originally associated with the Mediterranean region, this disease is present in many countries worldwide and may have been underreported due to its complicated diagnosis and scarce scientific literature, especially in regards to treatment. This study aims to review IPSID clinical features, therapeutic options, and treatment outcomes to help physicians identify and treat IPSID. Using PRISMA guidelines, a systematic review of articles was conducted on PubMed database with search terms including IPSID, therapy, treatment, and outcomes. Inclusion and exclusion criteria were used to select 33 English language articles published from the year 2000-2020 that included relevant clinical information about IPSID treatment. Data were extracted independently by at least two authors to reduce the introduction of potential bias. There were 22 case reports, 7 reviews, 1 research article, 1 prospective study, 1 letter to the editor and 1 memoriam in which 76 patients were identified. Epidemiological analysis showed a mean patient age of 32 years old, 2.4:1 mal to female ratio and heterogeneous ethnicities, with 16 Europeans (43.2%) and 12 Asians (32.4%). Chief symptoms included chronic diarrhea (53/76, 69.7%), weight loss (49/76, 64.4%), malabsorption (38/76, 50%), abdominal pain (32/76, 42.1%), and finger clubbing (24/76, 31.6%). Patients stratified into the early disease stage (Galian A) were treated with tetracycline antibiotics, corticosteroids, and non-pharmacological supplements with mostly with complete or partial remission. Late stages (Galian B or C), were treated mostly with anthracycline-based chemotherapy, and occasionally surgery, radiotherapy, or rituximab. This work offers a targeted approach to diagnosing and treating IPSID to aid physicians and serve as a treatment guideline recommendation for future public policies and clinical studies.
Topics: Adult; Anti-Bacterial Agents; Diarrhea; Humans; Immunoproliferative Small Intestinal Disease
PubMed: 34270561
DOI: 10.1371/journal.pone.0253695 -
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 -
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 -
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 -
JAMA Network Open Apr 2021A thorough understanding of the optimal role and sequence of agents for treatment of multiple myeloma (MM) requires knowledge of the use and rate of postprotocol...
IMPORTANCE
A thorough understanding of the optimal role and sequence of agents for treatment of multiple myeloma (MM) requires knowledge of the use and rate of postprotocol therapies in randomized clinical trials (RCTs).
OBJECTIVES
To examine the proportion of MM RCTs that reported postprotocol therapies and, among those, the percentage of patients who received no further therapy and how treatments differed between the control and intervention arms.
EVIDENCE REVIEW
The reporting of postprotocol therapies was systematically assessed in published MM RCTs using 3 databases (PubMed, Embase, and Cochrane Registry of Controlled Trials) for MM RCTs from January 1, 2005, to December 30, 2019. All MM RCTs were included, and all other studies, such as editorials, nonrandomized studies, and review articles, were excluded.
FINDINGS
A total of 103 RCTs were identified (47 251 patients); of these, 45 (43.7%) reported subsequent treatments in that publication or in any subsequent publication. Trials funded by pharmaceutical companies (26 of 47 [55.3%]) were more likely to report subsequent treatments than cooperative group studies (19 of 56 [33.9%]) (χ21,103 = 4.8; P = .03). Differences were found in the treatments received between the intervention and control arms of RCTs. When data were reported, 5150 of 9351 patients (54.9%) in RCTs of newly diagnosed MM and 2197 of 4501 patients (48.8%) in RCTs of relapsed/refractory MM received any subsequent therapy.
CONCLUSIONS AND RELEVANCE
Postprotocol therapies in MM RCTs are often not reported and, when they are, many patients receive no further therapy. Reporting guidelines for postprotocol therapies are needed.
Topics: Aftercare; Antineoplastic Combined Chemotherapy Protocols; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Oligonucleotides; Progression-Free Survival; Randomized Controlled Trials as Topic; Research Design; Standard of Care
PubMed: 33909053
DOI: 10.1001/jamanetworkopen.2021.8084