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

Abstract

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...

Peripheral Neuropathy under Oncologic Therapies: A Literature Review on Pathogenetic Mechanisms

“…Bortezomib is an N-protected dipeptide containing a boronic acid instead of a carboxylic acid and is an anti-cancer drug for the treatment of multiple myeloma and mantle cell lymphoma as first and further line treatment, often co-administered within a complex medical protocol together with other medications [ 100 , 101 ]. Together with carfilzomib, bortezomib is a reversible proteasome inhibitor thank to its boron atom which binds the catalytic site of the26S proteasome [ 100 , 102 ].with high affinity and specificity, blocking the degradation of cellular proteins and ridding cells of abnormal or misfolded proteins.…”

Retrospective Analysis of Presentation, Treatment, and Outcomes of Multiple Myeloma at a Large Public Referral Hospital in Eldoret, Kenya

“… 4 For transplant-ineligible patients, continuous VRD therapy has been shown to have an encouraging median OS of 71 months. 5 Other agents used in the treatment of MM include thalidomide, prednisolone, cyclophosphamide, and melphalan. 6 , 7 Despite development of national guidelines for diagnosis and treatment of MM in Kenya, 8 patients are often not able to receive stem-cell transplantation, and access to novel agents such as bortezomib and lenalidomide is limited.…”

<p>Qualitative Study of Factors Affecting Patient, Caregiver and Physician Preferences for Treatment of Myeloma and Indolent Lymphoma</p>

“…4,5 Most myeloma treatment regimens are triplet-based or quadruplet-based regimens comprising a proteasome inhibitor, an immunomodulatory agent, a steroid or a monoclonal antibody. 6,7 For the indolent lymphomas, treatment options range from conventional chemotherapy to monoclonal antibodies and, more recently, targeted therapies. 8,9 Unfortunately, there is a dearth of high-quality evidence directly comparing available treatment options, leaving comparative data scarce.…”