The role of auto-SCT in the treatment of multiple myeloma (MM) in the era of novel agents continues to evolve. It is now clear that the depth of response and clinical outcomes have significantly improved as a result of the combination of these strategies. However, not all patients with MM who undergo auto-SCT are able to sustain a meaningful response and 20% of patients relapse shortly after auto-SCT. In this study, we aimed to assess the impact of early relapse (ER) after auto-SCT on OS for MM patients undergoing single auto-SCT who had received novel agent-based induction regimens. All consecutive patients with MM undergoing single auto-SCT from January 2002 to September 2012 who had novel induction therapy were evaluated. A total of 184 patients were identified. The median OS and PFS for the group of transplanted patients were 93 and 25.4 months, respectively. Median time to relapse was 17.2 months with 40% having relapsed at the time of analysis. ER (o 12 months post auto-SCT) was seen in 27 (36%) out of 75 patients who had relapsed, and median OS was significantly shorter than in those with non-ER. Multivariate analysis showed ER as the major independent prognostic factor for OS. On the basis of these findings, we conclude that not only attainment of a good response, but sustainability of it, appears to be a major prognostic variable in MM in the era of novel therapy. Patients with ER post auto-SCT should biologically be characterized in prospective studies to better understand the mechanisms of resistance associated with this particular entity.
Summary
Light chain deposition disease (LCDD) is a monoclonal gammopathy characterized by nonamyloid deposition of immunoglobulin light chains in various organs. Most cases present with renal dysfunction, a ubiquitous feature of this disease, and in some instances, it may progress to end‐stage renal disease. Unfortunately, until now, no standard treatment has been established. The use of alkylating agents and steroids has been extensively reported. However, conventional chemotherapy response is generally limited with minor effects on kidney function. The use of novel agents such as bortezomib has shown a more rapid response with a dramatically important reduction of light chains in serum and/or urine in small series of cases. Furthermore, autologous stem cell transplantation has been reported as a feasible strategy in LCDD, able to prolong the dialysis‐free survival. Nonetheless, toxicity from these therapies should be considered carefully because most of patients might present with kidney dysfunction that could limit the use of some agents.
Immunoparesis and polyclonal immunoglobulin recovery have been recently described as common indicators of immune dysfunction in patients with multiple myeloma. In the present study, we aimed to assess the impact of immunoparesis and polyclonal immunoglobulin recovery at day-100 post autologous stem cell transplant (auto-SCT) on clinical outcomes. A total of 302 patients were included for the analysis of immunoparesis, and 197 were evaluable for polyclonal immunoglobulin recovery evaluation. Immunoparesis was observed in 93.5% of cases, with 47% of cases having polyclonal immunoglobulin recovery at 12 months post auto-SCT. Median overall and progression-free survival were longer in the group of patients with complete or partial normalization of polyclonal immunoglobulins. Patients receiving consolidation had a lower level of polyclonal reconstitution. In conclusion, polyclonal immunoglobulin recovery by 12 months post-auto-SCT is associated with superior overall and progression free survival in patients with MM. Efforts to better enhance polyclonal recovery deserve further investigation.
Cytogenetic analyses have been historically limited in Waldenström’s macroglobulinemia (WM) by the difficulty to obtain tumor metaphases. Thus, few recurrent karyotypic abnormalities have been reported and the molecular consequences of these imbalances are largely unknown. We used an array-based comparative genomic hybridization approach to better characterize the recurrent chromosome abnormalities associated with WM pathogenesis and to compare them with the publicly available findings in other B-cell neoplasias. The majority of the recurrent chromosome abnormalities identified in WM were shared with marginal zone lymphomas (MZL), as deletions of 6q23 and 13q14 and gains of 3q13-q28, 6p and 18q. On the other hand, gains of 4q and 8q were recurrently identified in WM but have not been described as being common abnormalities in MZL. The genetic consequences of these specific abnormalities remain elusive and further studies are critical to refine the search and to precise the molecular pathways affected by these abnormalities.
Recently, the occurrence of oligoclonal and monoclonal bands (OB/MB) unrelated to the original clone has been reported in patients with multiple myeloma who undergo autologous stem cell transplant (ASCT) and/or receive treatment with novel agents. The aim of our study was to assess the impact of OB/MB occurrence on overall (OS) and progression-free survival (PFS) for patients with MM undergoing single ASCT at our institution. All consecutive patients with documented MM undergoing single ASCT from January 2000 to December 2012 were evaluated. Ninety-nine patients (11.8%) developed OB/MB at day 100 post-ASCT (32.3%, OB and 67.7%, MB). Multivariate analysis identified the development of OBs/MBs as an independent favorable prognostic factor for OS and PFS (p = 0.008 and 0.012, respectively). In conclusion, the occurrence of OB/MB is an important prognostic factor in patients with MM who undergo ASCT. Its impact on clinical outcomes should be prospectively validated and its biological significance further elucidated.
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