Clinical and prognostic significance of t(4;14) translocation in multiple myeloma in the era of novel agents
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ORIGINAL ARTICLE
Clinical and prognostic significance of t(4;14) translocation in multiple myeloma in the era of novel agents Shuku Sato1,2 · Wataru Kamata1 · Satomi Okada1 · Yotaro Tamai1 Received: 22 June 2020 / Revised: 4 September 2020 / Accepted: 10 September 2020 © Japanese Society of Hematology 2020
Abstract Translocation t(4;14) is an independent prognostic factor for adverse outcome in multiple myeloma (MM). However, reports concerning the therapeutic effects of novel drugs on t(4;14) MM are few. We retrospectively investigated the clinical and prognostic significance of symptomatic MM cases with t(4;14) treated with novel therapies. Ninety-three patients (IgG, 56; IgA, 23; BjP, 14) newly diagnosed with MM were included (median age, 71 years; median observation period, 27.8 months). t(4;14) MM was diagnosed in 17 (IgG, 7; IgA, 9; BjP, 1) patients (18%). An association between t(4;14) and the IgA isotype was confirmed (p = 0.02). Overall survival (OS) at 3 years was lower in the t(4;14) patients than without t(4;14) group (81.2% vs 66.7%, p = 0.04). Multivariate analysis showed that t(4;14) was an independent predictor of OS (hazard ratio [HR], 7.58; 95.0% confidence interval [CI], 1.43–39.9; p = 0.0017). The ORR after autologous blood stem cell transplantation (ASCT) did not differ with or without t(4;14); progression-free survival tended to be prolonged in the group without t(4;14) (p = 0.088). Thus, even in the era of novel drugs, t(4;14) MM still has a poor prognosis, and triplet consolidation therapy should be continued. Keywords Multiple myeloma · t(4;14) translocation · Novel drugs · Daratumumab · Prognosis · Overall survival · Overall response rate
Introduction In multiple myeloma (MM), heterogenous chromosome translocation into the immunoglobulin heavy (IgH) chain switch region is frequently observed [1, 2]. Translocation into the IgH locus has been identified in ~ 47% of MM patients and cell lines studied [3]. Frequently involved partner chromosomes/loci are 4q16 (FGFR3/MMSET) (12–15%), 11q13 (CCND1) (15–20%), and 16q23 (MAF) (3%) [4]. The t(4;14) translocation is associated with FGFR3 and multiple myeloma SET domain (MMSET) and can be detected by fluorescence in situ hybridization (FISH) [5–7]. In the revised-international staging system (R-ISS) proposed * Shuku Sato [email protected] 1
Division of Hematology, Shonan Kamakura General Hospital, 1370‑1 Okamoto, Kamakura, Kanagawa 247‑0072, Japan
Division of Hematology, Shonan Kamakura General Hospital, 1370‑1 Okamoto, Kamakura, Kanagawa 247‑8533, Japan
2
by Palmbo et al. t(4;14), translocation is one of the high-risk chromosomal abnormalities (CA), which along with p53 and t(14;16) translocation is associated with poor prognosis, and is therefore clinically important [8]. Before the era of novel drugs such as bortezomib and lenalidomide, t(4;14) was associated with poor prognosis, requiring intensive chemotherapy and autologous transplantation [9]. According to previous reports, bortezomib seems to improve the negative prognostic
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