How I treat first relapse of myeloma

Abstract

The standard treatment of relapsed multiple myeloma has been either lenalidomide-dexamethasone (RD) or bortezomib-dexamethasone (VD) but it is changing rapidly for 2 reasons. First, lenalidomide and bortezomib are currently used in frontline treatment and many patients become resistant to these agents early in the course of their disease. Second, 6 second-line new agents have been recently developed and offer new possibilities (pomalidomide, carfilzomib and ixazomib, panobinostat, elotuzumab, and daratumumab). Recent randomized studies have shown that triple combinations adding 1 of these new agents (except pomalidomide) to the RD or VD regimens were superior to the double combinations in terms of response rate and progression-free survival (PFS). Their place in the treatment of first relapse is discussed here. Among these agents, daratumumab is clearly a breakthrough and daratumumab-based combinations might become the preferred option in the near future. However, all of these drugs are expensive and are not available or affordable in all countries. We propose a decision algorithm for first relapse in fit patients with the objective of achieving the best PFS. The choice of salvage regimen is based on lenalidomide/bortezomib resistance, daratumumab availability, and cost. Autologous transplantation should be considered in younger patients if not used upfront.

UBE2G1 Governs the Destruction of Cereblon Neomorphic Substrates

“…The clinical course of multiple myeloma typically follows a recurring pattern of remission and relapse with resistance to IMiD drugs based combination regimens (Harousseau and Attal, 2017). Such relapse is not frequently associated with cereblon downregulation and/or mutation (Kortum et al, 2016; Qian et al, 2018) (Zhu et al, 2011)Hence, we reasoned that resistance to IMiD drugs in myeloma could be ascribed to reduced degradation of IKZF1 and IKZF3 as a result of inactivation of other essential components of the CRL4 CRBN ligase complex, for instance the E2 ubiquitin conjugation enzyme.…”

Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma

“…3,4 Efficacy results from phase 3 studies of novel combination therapies in lenalidomide-refractory patients remain unsatisfactory, and recent studies of lenalidomide-based combination therapies in RRMM exclude lenalidomide-refractory patients. [5][6][7][8][9][10] Daratumumab is a human immunoglobulin Gk (IgGk) monoclonal antibody targeting CD38 with a direct on-tumor [11][12][13][14] and immunomodulatory mechanism of action. [15][16][17] Daratumumab is approved in many countries as a monotherapy and in combination with standard-of-care regimens in RRMM and in nontransplant newly diagnosed multiple myeloma (NDMM).…”

Prolonged survival after second autologous transplantation and lenalidomide maintenance for salvage treatment of myeloma patients at first relapse after prior autograft

“…[1][2][3][4][5][6][7][8][9] With the incorporation of novel agents into this strategy, progression-free survival (PFS) and overall survival (OS) rates of such patients have markedly improved within the last decade. [10][11][12][13][14][15] However, almost all patients with MM will ultimately relapse at some stage following initial therapy, the majority within 3 years after ASCT, and no plateau is observed in their OS. 2,3,6,16 The optimal treatment for MM patients relapsing after first-line treatment including ASCT is less clear.…”