Role of consolidation therapy in transplant eligible multiple myeloma patients.

The role of high-dose therapy and autologous stem-cell transplantation (ASCT) in the treatment of multiple myeloma (MM) has continued to evolve in recent years. The novel agents thalidomide, bortezomib, and lenalidomide have been successfully incorporated into induction therapy in preparation for ASCT and are currently being investigated also as post-ASCT consolidation and maintenance therapy. Consolidation treatment is generally short term and aims to increase the frequency and depth of response obtained with the previous treatment phases, including novel agent-based induction therapy and ASCT. This review will focus on recent trials of novel agents as post-ASCT consolidation therapy, offering an overview of pros and cons of this new treatment strategy in the ASCT sequence for MM patients

Peripheral neuropathy induced by subcutaneous bortezomib-based induction therapy for newly diagnosed multiple myeloma.

No abstract available

Long-term follow-up after autologous stem cell transplantation for light- and heavy-chain deposition disease.

Monoclonal Ig deposition disease (MIDD) is a broad and uncommon entity, including light chain deposition disease (LCDD), light- and heavy-chain deposition disease and heavy-chain deposition disease.1 Overall, the kidney is the major target organ, the clinical picture being most frequently characterised by nephrotic syndrome, hypertension and renal failure.2 Light-chain Fanconi syndrome due to proximal tubular involvement may also occur, and typically manifests with type II renal tubular acidosis, hypophosphatemia, glycosuria and hypouricemia. Heart, liver and other organs are less frequently involved.3, 4 In approximately one-third of patients with MIDD the underlying clone of monoclonal plasma cells cannot be routinely detected.2 However, recent availability of serum free light chain (FLC) assay has allowed to demonstration of the presence of increased monoclonal FLC in virtually all patients.5 Treatment strategies in these patients have been highly variable, ranging from steroids with or without chemotherapy2 to high-dose therapy followed by autologous stem-cell transplantation (ASCT).5, 6 We retrospectively analyzed the outcomes of 8 consecutive patients who were admitted to our Institute from 1993 to 2006 and received a diagnosis of MIDD, as confirmed by kidney biopsy. Additional investigations to confirm the diagnosis included light microscopy, congo red staining, immunofluorescence with anti-\u3ba and anti-\u3bb antibodies and EM; immunohistochemistry with antibodies directed against plasma cell-associated Ags was performed, when appropriate

Gene expression analysis of newly diagnosed Multiple Myeloma (MM) patients carrying amplified MDM4 and/or deleted p5

Abstract The p53 tumor suppressor pathway is tightly kept in check or completely silenced in cancer cells. A potent inhibitor of p53 is MDM4, which is located on chr.1q: it is critical for the control of p53 activity during the response to stress and is often amplified in several types of cancer. Since both del(17p) and amp(1q) identify a subgroup of high-risk MM pts, even when the novel agents are part of up-front treatment strategy, we molecularly analyzed a subgroup of MM patients treated with bortezomib-thalidomide-dexamethasone (VTD) and autologous stem cell transplantation (ASCT) in order to investigate mechanisms which might be activated in myeloma plasma cells to direct and/or indirect limit the p53 function. CD138+ plasma cells obtained at diagnosis from 61 pts, subsequently treated with VTD and ASCT were analysed by means of GEP and unpaired analysis of CNA (Affymetrix U133 Plus2.0 and 6.0 SNP arrays). Nineteen out of 61 pts (31%) carried a minimal amplification region on chr.1q, harboring MDM4. Eight out of 61 pts (13%) carried a 482 Kb minimal deletion region on chr.17 harboring TP53. To explore the involvement of the p53 pathway in MM, pts were stratified according to the presence of amplified MDM4 and/or deleted p53 (group A, 24 pts) or the absence of both these abnormalities (group B, 37 pts). Baseline clinical characteristics were homogeneous, except for a higher rate of ≤ 3 bone lesions in pts of group A. The rate of best complete or near complete response was 40% in group A and 14% in group B (p = 0.04). With a median follow-up of 36 months, the risk of progression was 46% for pts in group A and 19% for those in group B (p = 0.03). The average number of aberrations per group was overall higher in group A as compared to group B (165 vs. 103 CNAs, p =0.03). A comparison of expression profiles of the two subgroups of pts highlighted a deregulated expression of genes involved in the mechanisms of response to genotoxic stress, i.e. of damage sensor genes (ATM, RAD9, RAD 50, ATRip), of damage signal mediator genes (H2AFX, 14-3-3), of genes involved in regulation of cell proliferation (CDK6, CDC25, CCND2) and of anti-apoptotic genes (BCL2, p73) (one-way ANOVA plus multiple-test correction with FDR &amp;lt;0,05). Finally, this group of pts significantly over-express the transcription factor YY1, which is known to interact with p53, thus inhibiting its transcriptional activity. In conclusion, pts carrying amplified MDM4 and/or deleted p53 showed a significantly higher number of CNAs and the significant over-expression of genes involved in the response mechanisms to genotoxic stress, as compared to pts lacking these chromosomal aberrations. This might account for the worse outcome of patients harboring del(17p) and/or amp(1q). The MDM4 locus amplification and the YY1 over-expression might contribute to maintain p53 in an OFF state by an indirect mechanism. Supported by: Fondazione Del Monte di Bo e Ra, Ateneo RFO grants (M.C.) BolognAIL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1873. doi:1538-7445.AM2012-1873</jats:p