Prognostic Impact of Chromosomal Abnormalities in Elderly Patients with Multiple Myeloma Treated with High-Dose Melphalan (MEL140) and Autologous Stem Cell Transplantation.

Background: Although chromosomal aberrations (CA) have emerged as important outcome predictors in multiple myeloma (MM), the prognostic significance of many recurring genomic changes is still unknown. Moreover, there is only scarce data on the implication of chromosomal abnormalities in elderly patients (pts.) receiving high-dose chemotherapy (HD-CTX) followed by autologous stem cell transplantation (ASCT). Aims: To evaluate the prognostic relevance of recurring chromosomal aberrations as detected by cIg-FISH for elderly pts. with MM receiving HD-CTX and ASCT. Materials: Between 05/2001 and 08/2006, 549 pts. 60–70 yrs. of age with newly diagnosed symptomatic MM entered the DSMM II trial of the Deutsche Studiengruppe Multiples Myelom to receive two cycles of HD-CTX (melphalan 140 mg/sqm) followed by ASCT after 3–4 cycles of dexamethason-based induction chemotherapy (IC; arm A1) or no IC (arm A2). cIg-FISH and DNA probes mapping to chromosome bands 1q21.2, 9q34, 11q25, 13q14, 14q32, 17p13, and 22q11 were applied to all pts. from whom sufficient bone marrow specimen were obtained. 152 pts. with a median age of 65 yrs. for that information on all genomic loci was available were included in the present analysis. The clinical database was last updated in 04/2007.

Results: The median follow-up of time in the present series was 83 (1–264) weeks. Univariate analysis showed significantly shorter EFS in 14 out of 152 pts. (9%) with chromosome 17p13 deletion (17p−; 46 vs. 99 weeks, p<0.0001) and 18 out of 152 pts. (12%) with translocation t(4;14) (57 vs. 99 weeks, p=0.001). Clinical and laboratory variables as well as all other CA had no significant impact on EFS. Multivariate analysis revealed 17p− and t(4;14) as independent predictors of inferior EFS (p=0.0005 and p=0.01, respectively). OS was significantly shorter in pts. with 17p− (99 vs. 219 weeks, p=0.001) and in 17 out of 152 pts. (11%) with deletion of chromosome band 22q11 (127 weeks vs. not reached, p=0.002). There was a trend towards a shorter OS in pts. with t(4;14).

Conclusions: Our data suggest that HD-CTX and ASCT does not provide long-term disease control in elderly pts. with t(4;14) or 17p−. Therefore, HD-CTX and ASCT cannot be recommended for these high-risk pts. (overall ∼20% of cases). 13q− and +1q21.2 were not prognostic markers in the present study. Collection of clinical data and molecular cytogenetic analysis of further cases is ongoing.