-
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 -
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 -
Antibodies (Basel, Switzerland) May 2019Immunotherapy for multiple myeloma (MM) has been the focus in recent years due to its myeloma-specific immune responses. We reviewed the literature on non-Food and Drug... (Review)
Review
BACKGROUND
Immunotherapy for multiple myeloma (MM) has been the focus in recent years due to its myeloma-specific immune responses. We reviewed the literature on non-Food and Drug Administration (FDA) approved monoclonal antibodies (mAbs) to highlight future perspectives. We searched PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov to include phase I/II clinical trials. Data from 39 studies (1906 patients) were included. Of all the agents, Isatuximab (Isa, anti-CD38) and F50067 (anti-CXCR4) were the only mAbs to produce encouraging results as monotherapy with overall response rates (ORRs) of 66.7% and 32% respectively. Isa showed activity when used in combination with lenalidomide (Len) and dexamethasone (Dex), producing a clinical benefit rate (CBR) of 83%. Additionally, Isa used in combination with pomalidomide (Pom) and Dex resulted in a CBR of 73%. Indatuximab Ravtansine (anti-CD138 antibody-drug conjugate) produced an ORR of 78% and 79% when used in combination with Len-Dex and Pom-Dex, respectively.
CONCLUSIONS
Combination therapy using mAbs such as indatuximab, pembrolizumab, lorvotuzumab, siltuximab or dacetuzumab with chemotherapy agents produced better outcomes as compared to monotherapies. Further clinical trials investigating mAbs targeting CD38 used in combination therapy are warranted.
PubMed: 31544840
DOI: 10.3390/antib8020034 -
PharmacoEconomics Dec 2019Treatments for multiple myeloma (MM) have been rapidly evolving. Newly developed treatment regimens are likely to be more effective but also cost more than conventional...
BACKGROUND
Treatments for multiple myeloma (MM) have been rapidly evolving. Newly developed treatment regimens are likely to be more effective but also cost more than conventional therapies.
OBJECTIVE
We conducted a systematic review to compare the cost effectiveness of different classes of MM treatment.
METHODS
We searched the PubMed, MEDLINE, Web of Science, and EMBASE databases for studies published during 1990-2018 comparing the cost effectiveness of transplant, chemotherapeutic and novel MM treatments. Titles and abstracts were independently reviewed for eligibility by two investigators. The quality of the included studies was evaluated using the 16-item, validated Quality of Health Economics Studies instrument.
RESULTS
Twenty-four publications were included in the systematic review and summarized according to treatment regimen and line. For first-line treatment, transplant was the most cost-effective option for transplant-eligible MM patients [the incremental cost-effectiveness ratio (ICER) was $4053-€45,460 per quality-adjusted life-year (QALY) gained, and $3848-$72,852 per life-year gained (LYG)], and the ICER for novel agents compared with conventional chemotherapy was $59,076 per QALY and $220,681 per LYG. For second-line treatment, in comparisons of novel agent-based regimens, ICERs were inconsistent. However, bortezomib-based regimens, lenalidomide plus dexamethasone, and pomalidomide plus dexamethasone were each cost effective compared with dexamethasone alone (ICERs showed cost saving, £30,153 per QALY gained, and €39,911 per LYG, respectively).
CONCLUSIONS
For transplant-eligible MM patients, transplant is a cost-effective first-line treatment. More cost-effectiveness analyses comparing novel agents in the first-line treatment regimen are warranted to determine which agent or regimen is the most cost effective. In the second-line setting, it is unclear which novel agent-based regimen is most cost effective, but bortezomib-based regimens, lenalidomide plus dexamethasone, and pomalidomide plus dexamethasone were each cost effective compared with dexamethasone alone.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cost-Benefit Analysis; Humans; Multiple Myeloma; Quality-Adjusted Life Years; Stem Cell Transplantation
PubMed: 31392666
DOI: 10.1007/s40273-019-00828-y -
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 -
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 -
Future Oncology (London, England) 2015Novel drugs such as immunomodulators and proteasome inhibitors have improved the survival of patients with multiple myeloma. Like all therapeutic agents, appropriate... (Review)
Review
Novel drugs such as immunomodulators and proteasome inhibitors have improved the survival of patients with multiple myeloma. Like all therapeutic agents, appropriate dosing based on metabolism and clearance is important to maintain efficacy while avoiding toxicity. Hepatic impairment (HI) in multiple myeloma patients is rare but well described either due to disease or therapy-related factors. However, limited data are available on the appropriate use and dosing of the novel agent therapeutics in myeloma patients with HI. Furthermore, data on HI secondary to the novel agent toxicity are also sparse. This systematic review highlights the evidence on the use of novel agents like thalidomide, lenalidomide, pomalidomide, bortezomib and carfilzomib in patients with HI as well as their associated hepatic toxicities.
Topics: Antineoplastic Agents; Humans; Immunologic Factors; Liver Diseases; Multiple Myeloma; Proteasome Inhibitors; Treatment Outcome
PubMed: 25675129
DOI: 10.2217/fon.14.270