Abstract
Despite the introduction of novel agents, multiple myeloma remains incurable for most patients, necessitating further therapeutic options. Venetoclax, a selective BCL-2 inhibitor, had shown promising results in patients with translocation t(11;14), but questions remain open about its optimal use. We have contacted all Hungarian haematology centers for their experience treating t(11;14) myeloma patients with venetoclax. 58 patients were reported. 37 received venetoclax in the relapsed/refractory setting with few or no other therapeutic options available. 21 patients started venetoclax as salvage after failing to achieve satisfactory response to first line therapy. In the relapsed/refractory setting objective response rate (ORR) was 94%, median progression-free survival (PFS) 10.0 months and median overall survival (OS) 14.6 months. In reinduction patients, ORR was 100%, median PFS and OS were not reached. Importantly, we found no adverse effect of high risk features such as deletion 17p or renal failure, in fact renal failure ameliorated in 42% of the cases, including three patients who became dialysis independent. Our study also reports the highest number of plasma cell leukemia cases successfully treated with venetoclax published in literature, with refractory plasma cell leukemia patients achieving a median PFS of 10.0 and a median OS of 12.2 months.
Highlights
Despite advances in treatment in recent decades, multiple myeloma (MM) is still considered incurable, necessitating the development of newer therapeutic options
The concept of a second line salvage treatment is controversial: in the Myeloma XI, a large randomized trial, deeper post-autologous stem cell transplantation (ASCT) responses and progression-free survival (PFS) benefit has been demonstrated with second line proteasome inhibitor (PI) salvage, whereas in a recent retrospective study by Jurczyszyn et al found that immediate second-line ASCT was associated with better PFS [3,4]
Two different rationales behind venetoclax treatment were discernible: the majority, 37 patients received the drug in the R/R setting; whereas 21 patients underwent venetoclax therapy after suboptimal response to first line treatment, in preparation to ASCT
Summary
Despite advances in treatment in recent decades, multiple myeloma (MM) is still considered incurable, necessitating the development of newer therapeutic options. Triple class refractory patients—those refractory to an immunomodulatory drug (IMiD), a proteasome inhibitor (PI) and an anti-CD38 antibody—have a dismal outcome [1]. Treatment options in this group consist of pomalidomide combinations, selinexor-dexamethasone, belantamab mafodotin, melflufen and BCMA chimeric antigen receptor (CAR) T-cells. The concept of a second line salvage treatment is controversial: in the Myeloma XI, a large randomized trial, deeper post-ASCT responses and PFS benefit has been demonstrated with second line PI salvage, whereas in a recent retrospective study by Jurczyszyn et al found that immediate second-line ASCT was associated with better PFS [3,4]
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