Bortezomib a safety treatment for patients with Multiple Myeloma and Cystic Fibrosis

Abstract

Introduction:Bortezomib is a proteasome inhibitor that targets myeloma cell and its bone marrow microenvironment. Intravenous Bortezomib with or without dexamethasone, is effective and well tolerated in patients with relapsed/refractory multiple myeloma (MM).Methods:We used Bortezomib without corticosteroids, to avoid the risk of lung infection reactivations due to patient’s Pseudomonas aeruginosa colonization, in a MM patient with Cystic Fibrosis. Four 21-day cycles of Bortezomib were administrated at 1.3 mg/m2 on days 1,4,8 and 11 with a 10 day rest period. Treatment response and toxicity were evaluated.Results:After four cycles of therapy the patient achieved a very good partial response (VGPR) according to the IMWG response criteria, without clinically significant side effects.Conclusions:Bortezomib can be successfully utilized for the management of this difficult disease situation.

Dually Efficacious Medicine Against Fibrosis and Cancer

“…Interestingly, bortezomib was also revealed to down-regulate TGF-β/Smad/collagen signaling and to induce myofibroblast/HSC apoptosis, consequently attenuating the severity of histological fibrosis of the lung, liver and kidney in animal models [47,48]. Moreover, to minimize the risk of lung infection upon corticosteroid treatment, bortezomib has instead been utilized to manage patients with concomitant cystofibrosis and multiple myeloma, impressively achieving a very good partial response without serious adverse events [49].…”

“…The reciprocal association between fibrotic and neoplastic disorders has been noticed for decades through clinical observations and epidemiological investigations. While onco-pathogenesis frequently occurs following or with fibrosis exemplified by cirrhosis-linked hepatocellular carcinoma and cancer-associated fibroblasts in the tumor microenvironment, fibrotic disorders can conversely be induced by oncologic events such as skin sclerosis resulting from anti-cancer therapies of radiation and chemical agents [2,7,8,49]. Subsequently, accumulated pieces of biological evidence have revealed a number of aberrant molecular pathways that are shared by cancer and fibrosis, including oncogenic gene expressing signatures and epigenetic reprogramming among others [9,51].…”

Bortezomib for the treatment of previously untreated multiple myeloma

“…There are few data on bortezomib and fibrosis, but in vitro, in vivo and animal models of lung and skin fibrosis [47], and a case report of a MM patient with cystic fibrosis [48] suggested that bortezomib can be used safely in this setting.…”

Home is best. Self-administration of subcutaneous Bortezomib at home in patients with multiple myeloma - A mixed method study

“…This seems particularly important for treatments given frequently over a long period of time, such as subcutaneous (SC) Bortezomib that is used in several MM treatment combinations in patients with newly diagnosed as well as relapsed MM (Durie et al, 2016, Richardson et al, 2019, San Miguel et al, 2008, Spencer et al, 2018. Studies have shown that it is well-tolerated and only associated with few side effects (Cerchione et al, 2018, Gentilini et al, 2012, Vogl et al, 2017. Thus, it seems safe to offer patients self-administration of SC Bortezomib at home after thorough training.…”