Bortezomib Induced Peripheral Neuropathy: A Systematic Review of Phase III Trials
Bortezomib is a proteasome inhibitor commonly used for the treatment of multiple myeloma (MM). Its proven efficacy has resulted in increased survival rates in both the newly diagnosed and relapsed/refractory cohorts. Bortezomib-induced peripheral neuropathy (BIPN) is a disabling and common toxicity associated with this treatment, typically requiring dose reduction, delay or cessation of treatment protocol. It typically presents as numbness, tingling and paraesthesia manifesting in the peripheral domain in a glove and stocking distribution.
ConclusionThalidomide-based regimens are potential salvage treatment options for patients with RRMM, even with prior resistance to IMiDs.
Publication date: October 2019Source: Clinical Lymphoma Myeloma and Leukemia, Volume 19, Issue 10, SupplementAuthor(s): Sæmundur Rögnvaldsson, Vilhjálmur Steingrímsson, Ingemar Turesson, Magnus Björkholm, C. Ola Landgren, Sigurdur Kristinsson
Publication date: October 2019Source: Clinical Lymphoma Myeloma and Leukemia, Volume 19, Issue 10, SupplementAuthor(s): Tiffany Li, Hannah Timmins, Tracy King, Matthew Kiernan, David Goldstein, Susanna Park
Melphalan, prednisone and bortezomib (MPV) is a current standard in the treatment of transplant ineligible newly diagnosed multiple myeloma (TI NDMM) and has been used as a control arm in several recent phase 3 clinical trials. Bortezomib related peripheral neuropathy (PN) is a limiting factor to apply the original MPV dose and schedule and reduced intensity schedules have been used both in clinical practice and in clinical trials. However, the feasibility of full-dose MPV and the impact on efficacy of dose intensity in real world have not been described.
The use of bortezomib in treatment of multiple myeloma (MM) has become a backbone of many induction regimens. Its efficacy when given twice weekly is often at the expense of peripheral neuropathy (PN) despite of adopting subcutaneous (SQ) administration. In an attempt to reduce the impact on quality of life (QOL) without compromising response, studies using weekly bortezomib with cyclophosphamide and dexamethasone (VCD) or lenalidomide and dexamethasone (RVD-lite) in transplant ineligible patients have demonstrated to be effective treatment regimens.
In the present study, the effect and toxicity of 1.6mg/m2 and 1.3mg/m2 bortezomib BCD on multiple myeloma (MM) were analyzed retrospectively. From January 2016 to December 2018, 82 newly diagnosed MM patients received minimal 4 cycles of either 1.6mg/m2 (bortezomib 1.6mg/m2, d1, d8, d15, d22; cyclophosphamide 300 mg/m2 d1, d8, d15; dexamethasone 20 mg d1, d2, d8, d9, d15, d16, d22, d23; 35 days per cycle) or 1.3mg/m2 (bortezomib 1.3mg/m2, d1, d4, d8, d11; cyclophosphamide 300 mg/m2 d1, d8, d15; dexamethasone 20 mg d1, d2, d4, d5, d8, d9, d11, d12; 21 days per cycle) bortezomib BCD regimen.
Monoclonal gammopathy of undetermined significance (MGUS) is the precursor condition of multiple myeloma (MM) and related disorders. MGUS is relatively common and although it is often referred to as asymptomatic, individuals with MGUS have been reported to develop peripheral neuropathy (PN). However, the literature is unclear on the prevalence, implications, and even the existence of MGUS associated PN. Therefore, we were motivated to assess the prevalence and risk of PN in a large population of individuals with MGUS.
In this study we sought to identify mechanisms of disease development by comparing the immune tumor microenvironment (iTME) of patients with POEMS syndrome to that of patients with MGUS.
The combination of daratumumab (dara), subcutaneous (SC) bortezomib twice weekly, and dexamethasone (dex) [Dara-Vd] has become a common treatment for patients with relapsed and/or refractory multiple myeloma (MM) after the CASTOR trial data led to its inclusion in the NCCN guidelines. A common and notable non-hematologic adverse effect causing dose modifications, delays, or discontinuation of bortezomib in this regimen has been peripheral neuropathy (PN). This could impact a patient's quality of life or lead to suboptimal therapy.
Publication date: Available online 18 September 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Donald C. Moore, J. Tanner Ringley, David Nix, Ala’a Muslimani