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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3610-3611.
CORRESPONDENCE Survival of genetic subtypes of relapsed myeloma may be modulated by secondary eventsTo the editor:The biological heterogeneity of myeloma can be largely explained by genetic subtypes characterized by primary translocations, or trisomies of chromosomes 3, 5, 7, 9, 11, 15, 19, and 21. In newly diagnosed patients, it is well established that these genetic subtypes have different survival rates.1 However, the prevalence and survival of the main genetic subtypes in relapse patients is unknown. We studied the prevalence and survival according to the TC (the translocation and cyclin D) classification,2 which corresponds to the main genetic subtypes, in patients with relapsed myeloma entered into single-agent bortezomib trials (bortezomib cohort3). For comparison, we analyzed a large gene expression data set of newly diagnosed patients treated with total therapy II from the University of Arkansas for Medical Science (UAMS cohort).4 Gene expression profiling (GEP) was performed using the U133A and B chip (bortezomib cohort) and U133plus chip (UAMS cohorts) (Affymetrix, Santa Clara, CA). Raw gene expression data were log transformed, median centered, and analyzed using Genespring 7.0 (Agilent Technologies, Palo Alto, CA). Relevant gene expression data were extracted, TC classification was performed, and a proliferation index (PI) based on the expression of 7 genes (TYMS, TOP2A, CCNB1, KIAA0101, CKS1B, UBE2C, TRIP13) was calculated.2 The prevalence of the different TC classes in relapse patients was very similar to newly diagnosed patients (chi-square P = .25). Relapsed patients (bortezomib cohort) with t(11;14) had the worst survival when compared with patients with t(4;14), maf translocation, and hyperdiploidy who had similar survival (survival of t(11;14) versus others, log-rank P = .036) (Figure 1A). In contrast, newly diagnosed patients (UAMS cohort) with t(4;14) and maf translocations had the worst prognosis; t(11;14) and hyperdiploid patients had the best prognosis (log-rank P = .02) (Figure 1B). Of interest, a greater proportion of patients with relapsed than newly diagnosed t(11;14) has PI more than 2 (9% vs 0%, chi-square P = .04). In contrast, there is no difference between the PI of newly diagnosed and relapsed hyperdiploid multiple myeloma (MM) patients (TC D1, 1% vs 2%, P = .19), consistent with a more indolent nature of relapse in this genetic subtype.
Our observations suggest that although the composition of the various genetic subtypes at diagnosis and relapse appear similar, the prognosis of some subtypes (especially t(11;14)) can be markedly different at relapse when modulated by secondary events (eg, increased proliferation), whereas others (such as hyperdiploid MM) appear to behave similarly at diagnosis and relapse. Our observation also has important therapeutic implications as it suggests relapsed t(11;14) should be treated aggressively and drug combinations or addition of new agents may be more appropriate for these patients. On the other hand, bortezomib seemed to be an effective therapy in relapsed t(4;14) patients, improving the prognosis of these patients to that of genetic subgroups with good prognosis. Our observations highlight the fact that different treatment strategies may be needed for newly diagnosed and relapsed patients even within the same genetic subtypes. Authorship Conflict-of-interest disclosure: G.M. and B.B. are employees of Millenium Pharmaceuticals, Inc. Correspondence: Leif Bergsagel, MD, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259; e-mail: bergsagel.leif{at}mayo.edu.
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| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
