First-line therapy for non-transplant eligible patients with multiple myeloma: direct and adjusted indirect comparison of treatment regimens on the existing market in Germany

Kuhr, Kathrin; Wirth, Daniel; Srivastava, Kunal; Lehmacher, Walter; Hellmich, Martin

doi:10.1007/s00228-015-1998-5

Cited by 6 publications

(8 citation statements)

References 30 publications

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“…Their results, however, showed that there was no difference in PFS between maintenance and no-maintenance approaches. 42 Therefore, we believe that it is appropriate to combine these trials, as performed previously, 11,43 and the results of our sensitivity analysis confirm this assumption (see Online Supplementary Appendix 7 ).…”

Section: Discussionsupporting

confidence: 79%

“…Our results align with the results from Kuhr et al . 11 in that VMP and MPT are more effective than MP. Our results also confirm the conclusion from Weisel et al .…”

Section: Discussionmentioning

confidence: 98%

“…12 did not find an overlap between VMP and Rd in their sensitivity analyses including six and twelve additional studies, is most likely because they used a fixed effect model for their analysis. A random effects model, like that used in our analysis and by Kuhr et al ., 11 is, however, more appropriate, as this model allows for the between study-heterogeneity in the additional studies.…”

Section: Discussionmentioning

confidence: 99%

“…There are currently two systematic literature reviews (SLRs) and NMAs available for first-line NTE NDMM treatments. 11,12 Due to the timing of their searches and selection criteria, these reviews did not, however, include all currently available treatments (e.g. VRd, VMPT-VT, DaraVMP) and RCT evidence (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of first-line treatments for multiple myeloma patients not eligible for stem cell transplantation: a network meta-analysis

et al. 2019

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Decision making for patients with multiple myeloma (MM) not transplant eligible (NTE) is complicated by a lack of head-to-head comparisons of standards of care, the increase in the choice of treatment modalities, and the promising results that are rapidly evolving from studies with novel regimens. To support evidence-based decision making, we performed a network meta-analysis for NTE MM patients that synthesizes direct and indirect evidence and enables a comparison of all treatments. Relevant randomized clinical trials were identified by a systematic literature review in EMBASE®, MEDLINE®, MEDLINE®-in-Process and the Cochrane Central Register of Controlled Trials for January 1999 to March 2016. Efficacy outcomes [i.e. the hazard ratio (HR) and 95% confidence interval (95%CI) for progression-free survival] were extracted and synthesized in a random effects network-meta analysis. In total, 24 studies were identified including 21 treatments. According to the network-meta analysis, the HR for progression-free survival was favorable for all NTE MM treatments compared to dexamethasone (HR: 0.19-0.90). Daratumumab-bortezomib-melphalan-prednisone and bortezomib-melphalan-prednisone-thalidomide with bortezomib-thalidomide maintenance were identified as the most effective treatments (HR: 0.19, 95%CI: 0.08-0.45 and HR: 0.22, 95%CI: 0.10-0.51, respectively). HR and 95%CI for currently recommended treatments, bortezomib-lenalidomide-dexamethasone, bortezomib-melphalan-prednisone, and lenalidomide-dexamethasone compared to dexamethasone, were 0.31 (0.16-0.59), 0.39 (0.20-0.75), and 0.44 (0.29-0.65), respectively. In addition to identifying the most effective treatment options, we illustrate the additional value and evidence of network meta-analysis in clinical practice. In the current treatment landscape, the results of network meta-analysis may support evidence-based decisions and ultimately help to optimize treatment and outcomes of NTE MM patients.

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Section: Discussionsupporting

confidence: 79%

“…Our results align with the results from Kuhr et al . 11 in that VMP and MPT are more effective than MP. Our results also confirm the conclusion from Weisel et al .…”

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy of first-line treatments for multiple myeloma patients not eligible for stem cell transplantation: a network meta-analysis

et al. 2019

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“…The next step forward in the treatment armamentarium was the use of high-dose mephalan followed by autologous stem cell transplant in young patients, with mephalan-prednisolone remaining the standard of care in the elderly 8. Significant developments have occurred in recent years with the availability of novel agents including arsenic trioxide and farnesyltransferase inhibitor 2-methoxyestradiol 9. Over the past decade, with the introduction of immune-modulating drugs such as thalidomide, lenalidomide, pamlidomide and protease inhibitors such as bortezomib and carfilzomib, the treatment of myeloma has been transformed.…”

Section: Discussionmentioning

confidence: 99%

Multiple myeloma presenting with bilateral ankle pain (microangiopathy) and complicated by streptococcal meningitis andPneumocystis cariniipneumonia

2017

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Multiple myeloma is characterised by the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin. This clone of plasma cells proliferates in the bone marrow, resulting in extensive skeletal destruction with osteolytic lesions, osteopenia and pathological fractures. Additional disease-related complications include hypercalcaemia, renal insufficiency, anaemia and infection. We present the case of a 64-year-old woman presenting with rapid onset, painful distal symmetrical lower limb weakness and an acute kidney injury. Owing to her IgG κ paraprotein (kappa light chain 4620, kappa:lambda ratio 826), she was diagnosed with probable plasma cell myeloma. This diagnosis was confirmed following a trephine biopsy. She required renal replacement therapy, inotropic support and a percutaneous tracheostomy. She became acutely confused with a Glasgow Coma Scale score of 10/15 and a CT head showed no acute pathology. Further investigation with a lumbar puncture confirmed the diagnosis of streptococcal meningitis. She was treated with intravenous acyclovir, ceftriaxone and fluconazole. Her non-bronchoalveolar lavage revealed a diagnosis of Pneumocystis carinii pneumonia and she required treatment with co-trimoxazole. This case report discusses the clinical presentation, diagnostic algorithm and treatment of myeloma. This manuscript offers an important clinical reminder to consider myeloma in the differential diagnosis in patients presenting with bone pain and acute kidney injury.

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Multiple drug combinations of bortezomib, lenalidomide, and thalidomide for first-line treatment in adults with transplant-ineligible multiple myeloma: a network meta-analysis

Piechotta

Jakob

Langer

et al. 2019

Cochrane Database of Systematic Reviews

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BackgroundMultiple myeloma is a bone marrow-based hematological malignancy accounting for approximately two per cent of cancers. First-line treatment for transplant-ineligible individuals consists of multiple drug 18/04 Multiple drug combinations of bortezomib, lenalidomide, and thalidomide for first-line treatment in adults with tran... 18/04 Multiple drug combinations of bortezomib, lenalidomide, and thalidomide for first-line treatment in adults with tran... * V stands for 'Velcade®', the proprietary name of bortezomib. ** R stands for 'Revlimid®', the proprietary name of lenalidomide.Nowadays, the recommended treatment for adults with transplant-ineligible newly diagnosed multiple myeloma (NDMM) is either a double-or a triple-drug combination therapy (Kumar 2018; Moreau 2017), consisting of: immunomodulatory drug (R or T) in combination with a glucocorticoid (D, P) or glucocorticoid and alkylating agent (CD, CP or MP) proteasome inhibitor (V) in combination with a glucocorticoid (D, P) or glucocorticoid and alkylating agent (CD, CP or MP) immunomodulatory drug (R or T) in combination with proteasome inhibitor (V), and a glucocorticoid (D, P) or glucocorticoid and alkylating agent (CD, CP or MP) Regimens, which include either an immunomodulatory drug or a proteasome inhibitor will be referred to as double-drug combinations. We will refer to triple-drug combinations, when a immunomodulatory drug and a proteasome inhibitor is included in the regimen.Combinations of these interventions at any dose and by any route were compared to each other in a full network. We included trials with any treatment duration and divided treatment regimens between fixed and continuous therapies (Description of the intervention).To increase the amount of potential comparisons and to strengthen the network, we also included studies comparing the described double-or triple-drug combinations to the former standard treatment MP. As the aim of this review was to inform an application for the WHO list of essential medicines, the focus of this review was to compare the effectiveness and safety of V, R, and T. Therefore, if we identified additional new drugs for first-line treatment of multiple myeloma, these were excluded from the network and this review.We assumed that any participant that meets the inclusion criteria was, in principle, equally likely to be randomised to any of the eligible interventions. We planned to group interventions by evaluating different drug doses together as one drug of interest, according to the product characteristics.We excluded trials including participants receiving neither V, R, or T (triple or double combination) in at least one treatment arm, and trials including participants receiving no corticosteroid. We excluded trials evaluating the effectiveness and safety of the interventions of interest for supportive treatment during stem cell transplantation, or maintenance therapy, or both. Medications used to treat myeloma in subsequent lines of therapy might be the same as for first-line treatment, but to ens...

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First-line therapy for non-transplant eligible patients with multiple myeloma: direct and adjusted indirect comparison of treatment regimens on the existing market in Germany

Abstract: VMP and MPT seem more effective than MP, VMP was superior to MPT regarding response criteria and AEs. Our results may best be confirmed by a head-to-head trial of VMP vs. MPT.

Cited by 6 publications

References 30 publications

Efficacy of first-line treatments for multiple myeloma patients not eligible for stem cell transplantation: a network meta-analysis

Efficacy of first-line treatments for multiple myeloma patients not eligible for stem cell transplantation: a network meta-analysis

Multiple myeloma presenting with bilateral ankle pain (microangiopathy) and complicated by streptococcal meningitis andPneumocystis cariniipneumonia

Multiple drug combinations of bortezomib, lenalidomide, and thalidomide for first-line treatment in adults with transplant-ineligible multiple myeloma: a network meta-analysis

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