Newly diagnosed multiple myeloma patients carrying monoallelic deletion of the whole locus of immunoglobulin heavy chain gene have a better prognosis compared to those with t(4;14) and t(14;16).

The current study evaluated the prognostic significance of the monoallelic deletion of the whole locus of the immunoglobulin heavy-chain (w_del(IGH)) gene compared to translocations t(4;14) and t(14;16) among newly diagnosed multiple myeloma (MM) patients. We retrospectively analyzed clinical (age, gender, and staging) and laboratory data at diagnosis and the overall survival (OS) of 255 newly diagnosed MM patients carrying w_del(IGH) or translocations t(4;14) or t(14;16). Bone marrow samples were examined by morphological and sequential interphase fluorescense in situ hybridization analyses. Among 255 patients, 117 (45.8%) had w_del(IGH), 99 (38.8%) had t(4;14), and 39 (15.3%) had t(14;16). Mean age was 61.6 ± 11.6 years. Groups did not differ significantly in age, gender, or lactate dehydrogenase levels. Patients in the w_del(IGH) group presented more frequently at International Staging System stage I than at stage II/III. Patients in the w_del(IGH) group had significantly fewer additional chromosomal aberrations (1.58) than the other two groups (2.3 and 2.13 in the del(IGH), t(14;16) and t(4;14) groups, respectively, P < 0.0001). Furthermore, the w_del(IGH) group had significantly longer estimated median OS (9.47 years) compared to those with translocations t(14;16) (3.02 years, P = 0.002) or t(4;14) (4.18 years, P = 0.001), respectively. These findings suggest a potential prognostic significance of monoallelic deletion of IGH among these patients. Additional studies are needed to better understand the nature and mechanism of this prognostic factor.

Translocation t(11;14) in newly diagnosed patients with multiple myeloma: Is it always favorable?

The most common translocation in multiple myeloma (MM) is t(11;14)(q13;q32). According to several studies, this translocation represents a unique subset of patients with relatively favorable outcomes. Using combined analyses of morphology and fluorescence in situ hybridization (I-FISH), we examined the co-occurrence rates of t(11;14) with seven chromosomal aberrations (CAs), del(13q), del(17p), del(1p), gain(1q), multiple gains(1q), del(16q), and del(IGH), and assessed the effect of the different combinations on patient outcomes, with overall survival (OS) as the main outcome measure. Bone marrow samples and clinical data from 212 patients with MM with t(11;14) were analyzed. At least two additional CAs were found in 35% (75/205) of patients and a strong correlation between specific CAs. The occurrence of three CAs [multiple gains of (1q) (HR = 6.94, P = 0.001), del(1p) (HR = 4.47, P = 0.008), and del(IGH) (HR = 2.38, P = 0.002)] exerted a profoundly deleterious effect on median OS when compared with patients with t(11;14) only. Del(17p) and del(13q) have also exerted a deleterious effect albeit to a lesser extent (HR = 2.05, P = 0.07 and HR = 1.81, P = 0.03, respectively). When compared with t(11;14) alone, the addition of certain CAs lead to worse outcomes. These findings may have important clinical and biological implications. Patients with coexisting adverse lesions and t(11;14) may be considered at high risk and managed accordingly. © 2016 Wiley Periodicals, Inc.