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Neurological Sciences : Official... Sep 2023Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a reactivation of the human polyomavirus 2 (HPyV-2,... (Review)
Review
BACKGROUND
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a reactivation of the human polyomavirus 2 (HPyV-2, previously known as JCV) in immunosuppressed individuals. Few cases of PML have been described in multiple myeloma (MM) patients.
METHODS
We described a case of PML in a patient with MM with fatal worsening that occurred during SARS-CoV-2 infection. We also performed a literature review to update the 16 cases series of MM patients with PML already collected until April 2020.
RESULTS
A 79-year-old female patient with refractory IgA lambda MM in Pomalidomide- Cyclophosphamide-Dexamethasone regimen developed gradual lower limbs and left arm paresis along with a decreased consciousness 3.5 years after the MM diagnosis. Symptoms developed shortly after the recognition of hypogammaglobulinemia. After SARS-CoV-2 infection, her neurological status quickly worsened until she deceased. MRI features and JCV-positive PCR on CSF confirmed the PML diagnosis. Our literature review adds sixteen clinical cases of PML in MM published between May 2020 and March 2023 to the 16 cases already collected in the previously published review by Koutsavlis.
DISCUSSION
PML has been increasingly described in MM patients. It remains questionable if the HPyV-2 reactivation is determined by the severity of MM itself, by the effect of drugs or by a combination of both. SARS-CoV-2 infection may have a role in worsening PML in affected patients.
Topics: Humans; Female; Aged; Leukoencephalopathy, Progressive Multifocal; JC Virus; Multiple Myeloma; COVID-19; SARS-CoV-2
PubMed: 37421487
DOI: 10.1007/s10072-023-06944-0 -
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 -
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 -
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 -
Cancers Nov 2021Novel therapies for multiple myeloma (MM) promise to improve outcomes but are also associated with substantial increasing costs. Evidence regarding cost-effectiveness of... (Review)
Review
BACKGROUND
Novel therapies for multiple myeloma (MM) promise to improve outcomes but are also associated with substantial increasing costs. Evidence regarding cost-effectiveness of novel treatments is necessary, but a comprehensive up-to-date overview of the cost-effectiveness evidence of novel treatments is currently lacking.
METHODS
We searched Embase, Medline via Ovid, Web of Science and EconLIT ProQuest to identify all cost-effectiveness evaluations of novel pharmacological treatment of MM reporting cost per quality-adjusted life year (QALY) and cost per life year (LY) gained since 2005. Quality and completeness of reporting was assessed using the Consolidated Health Economic Evaluation Reporting Standards.
RESULTS
We identified 13 economic evaluations, comprising 32 comparisons. Our results show that novel agents generate additional LYs (range: 0.311-3.85) and QALYs (range: 0.1-2.85) compared to backbone regimens and 0.02 to 1.10 LYs and 0.01 to 0.91 QALYs for comparisons between regimens containing two novel agents. Lifetime healthcare costs ranged from USD 60,413 to 1,434,937 per patient. The cost-effectiveness ratios per QALY gained ranged from dominating to USD 1,369,062 for novel agents compared with backbone therapies and from dominating to USD 618,018 for comparisons between novel agents.
CONCLUSIONS
Cost-effectiveness ratios of novel agents were generally above current willingness-to-pay thresholds. To ensure access, cost-effectiveness should be improved or cost-effectiveness ratios above current thresholds should be accepted.
PubMed: 34830761
DOI: 10.3390/cancers13225606 -
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 -
Arthritis Research & Therapy Jun 2021New molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years,... (Review)
Review
New molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years, the achievement of one large phase 3 trial has led to the approval by drug agencies of the first drug licenced for SSc-related interstitial lung disease. Given this exciting time in the SSc field, we aimed to perform a systemic literature review of phase 1, phase 2 and phase 3 clinical trials and large observational studies about targeted therapies in SSc. We searched MEDLINE/PubMed, EMBASE, and ClinicalTrials.gov for clinical studies from 2016 with targeted therapies as the primary treatment in patients with SSc for skin or lung involvement as the primary clinical outcome measure. Details on the study characteristics, the trial drug used, the molecular target engaged by the trial drug, the inclusion criteria of the study, the treatment dose, the possibility of concomitant immunosuppression, the endpoints of the study, the duration of the study and the results obtained were reviewed. Of the 973 references identified, 21 (4 conference abstracts and 17 articles) were included in the systematic review. A total of 15 phase 1/phase 2 clinical trials, 2 phase 3 clinical trials and 2 observation studies were analysed. The drugs studied in phase 1/phase 2 studies included the following: inebilizumab, dabigatran, C-82, pomalidomide, rilonacept, romilkimab, tocilizumab, tofacitinib, pirfenidone, lenabasum, abatacept, belimumab, riociguat, SAR100842 and lanifibranor. All but 3 studies were performed in early diffuse SSc patients with different inclusion criteria, while 3 studies were performed in SSc patients with interstitial lung disease (ILD). Phase 3 clinical trials investigated nintedanib and tocilizumab. Nintedanib was investigated in SSc-ILD patients whereas tocilizumab focused on early diffuse SSc patients with inflammatory features. Two observational studies including > 50 patients with rituximab as the targeted drug were also evaluated. All these studies offer a real hope for SSc patients. The future challenges will be to customize patient-specific therapeutics with the goal to develop precision medicine for SSc.
Topics: Humans; Lung Diseases, Interstitial; Scleroderma, Diffuse; Scleroderma, Systemic
PubMed: 34074331
DOI: 10.1186/s13075-021-02536-5