Multiple Myeloma: Clinical Implications of Cytogenetic Aberrations on Selected Plasma Cells on Conventional Cytogenetics and Interphase Flourescence In Situ Hibridization (FISH)

We prospectively studied patients of multiple myeloma (MM) for presence of t(14q32), and del13q14 on FISH and numerical chromosomal abnormalities on conventional cytogenetics(CC).

Between February 2007 and June 2009, 90 previously untreated patients of MM were enrolled, Patient's median age was 55 years (range, 34 to 75 years) and 67 were males (M: F: 2.9: 1). 24 patients had ISS stage I, stage II-46 & 20 patients had stage III. Purified bone marrow plasma cells, using magnetic activated cell sorter with CD138 micro beads were used. Conventional cytogenetics for numerical chromosomal abnormalities and FISH for deletion 13q14 (RB-1) and 14q32 (IgH) translocations was carried out on these purified plasma cells. 65/90 (72%) patients received therapy; using novel agents, n=54 (thalidomide-dexamethasone (n=50), Lenalidomide-dexamethasone (n=4)) and melphalan, prednisolone and thalidomide (MPT, n=11). Response was evaluated post 4 cycles using EBMT response criteria.

Metaphases could be obtained on CC in 53/90 patients (58%); with numerical abnormalities in 21: hyperdiploid -16 & hypodiploid in 5. Del 13q14 and t (14q32) by FISH was present in 51 (56%) and 75 (83%) patients, respectively. t (14q32) was present more in patients with ISS-III (p<.008). Presence of del13q14 correlated with BM plasma cells >40% (P<.007) and Hb ≤9.2G/dl (p=.06). Following therapy, 49/65 patients (75.2%) achieved significant response (CR+VGPR+PR). Patients aged ≤55 years (P = 0.07), those with ISS- I (P <0.05), IgG-kappa (P<0.04) and with absence of del13q14 (P = 0.04) responded better. The median overall survival (OS) has not reached yet, median event-free survival (EFS) is 33 months (95% CI 18–48). Estimated OS and EFS at 2 years is 77% and 50 %, respectively. Durie Salmon stage IIIB (HR 3.6) and response to therapy (HR 7.8) were significant predictors of OS. For EFS - del13q14 (HR 2.7, P <0.036), response to therapy (HR 2.7,P<0.01) and use of novel agents (HR 3.1, (P<0.008) were important predictors.

Chromosomal abnormalities including IgH translocations and del13q14 with numerical chromosomal abnormalities are common in MM patients at diagnosis and can predict the treatment outcome and survival.

No relevant conflicts of interest to declare.