Advances in therapy of multiple myeloma

Bladé, Joan; Rosiñol, Laura

doi:10.1097/cco.0b013e3283136984

Cited by 36 publications

(28 citation statements)

References 53 publications

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“…11,12 Still, not all patients respond to these new drugs and, furthermore, some patients relapse quickly regardless of the previous response achievement, suggesting that some biological mechanisms of resistance emerge in such aggressive myeloma clones. Furthermore, the existence of a progenitor organization in primary MM that recapitulates maturation stages between B cells and plasma cells and that contributes to clinical resistance in relapsed myeloma patients has also been recognized.…”

Section: Discussionmentioning

confidence: 99%

Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents

Jiménez-Zepeda

Reece

Trudel

et al. 2014

Bone Marrow Transplant

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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.

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Section: Discussionmentioning

confidence: 99%

Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents

Jiménez-Zepeda

Reece

Trudel

et al. 2014

Bone Marrow Transplant

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“…Complete remission rates up to 40%, as well as a prolonged disease-free survival, have been achieved with high-dose melphalan. 1 The high-dose melphalan treatment-related mortality is below 5%. 2 Because of the highly variable clinical course of the disease when classified according to Salmon and Durie, cytogenetic data as well as b2-microglobulin and serum albumin level were introduced to state the clinical outcome more precisely.…”

Section: Introductionmentioning

confidence: 99%

Lack of CD56 expression on myeloma cells is not a marker for poor prognosis in patients treated by high-dose chemotherapy and is associated with translocation t(11;14)

Hundemer

Klein

Hose

et al. 2007

Bone Marrow Transplant

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Lack of CD56 expression was reported to be associated with a poor prognosis in multiple myeloma (MM) patients treated with conventional chemotherapy. Aim of our retrospective study was to analyse whether CD56 expression on MM cells reveals as a prognostic factor in patients treated with high-dose chemotherapy. MM cells of 99 patients prior to treatment with high-dose chemotherapy were analysed for CD56 expression by flow cytometry. Multivariable analysis of event-free survival in these patients showed no statistically significant difference between the CD56 À (n ¼ 28) and the CD56 þ (n ¼ 71) group. The lack of CD56 expression on MM cells of these patients correlated significantly with the presence of translocation (11;14) (t(11;14)) (estimated correlation coefficient ¼ 0.655 95%, confidence interval (0.481; 0.779)). In summary, our results indicate that lack of CD56 expression on MM cells is not a prognostic marker in patients treated with high-dose chemotherapy, but is associated with t(11;14).

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“…1,2 Thalidomide and its analogs are also being investigated in other hematologic malignancies and hematologic disorders for which there is no effective treatment such as mantle cell lymphoma, chronic lymphocytic leukemia, and myelodysplastic syndromes. 3 Thalidomide is not directly cytotoxic and the mechanisms through which it exerts its therapeutic benefits are not well defined and appear to be highly complex. Understanding the molecular basis of the effects of thalidomide is crucial in order to be able to design more efficient and less harmful analogs.…”

Section: Introductionmentioning

confidence: 99%

Thalidomide decreases gelatinase production by malignant B lymphoid cell lines through disruption of multiple integrin-mediated signaling pathways

Segarra¹,

Lozano²,

Corbera-Bellalta³

et al. 2009

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundThalidomide and its analogs are effective agents in the treatment of multiple myeloma. Since gelatinases (matrix metalloproteinases-2 and -9) play a crucial role in tumor progression, we explored the effect of thalidomide on gelatinase production by malignant B lymphoid cell lines. Design and MethodsWe investigated the effect of therapeutic doses of thalidomide on integrin-mediated production of gelatinases by malignant B lymphoid cell lines by gelatin zymography, western-blot, reverse transcriptase polymerase chain reaction and invasive capacity through Matrigel-coated Boyden chambers. We also explored the effect of thalidomide on the activation status of the main signaling pathways involved in this process. ResultsThalidomide strongly inhibited gelatinase production by B-cell lines and primary myeloma cells in response to fibronectin, the most efficient gelatinase inducer identified in lymphoid cells. Thalidomide disrupted integrin-mediated signaling pathways involved in gelatinase induction and release, such as Src and MAP-kinase ERK activation, resulting in decreased cell motility and invasiveness. Unexpectedly, treatment with thalidomide elicited an increase in fibronectin-induced Akt phosphorylation through phosphoinositide 3-kinase-independent pathways since thalidomide decreased fibronectin-induced phosphoinositide 3-kinase phosphorylation and reversed the inhibition of Akt phosphorylation achieved by the phosphoinositide 3-kinase inhibitors wortmannin and LY294002. ConclusionsDisruption of integrin-mediated signaling may be an important mechanism through which thalidomide and its analogs impair tumor cell interactions with the microenvironment. The unexpected effects of thalidomide on Akt activation indicate the need for further studies to elucidate whether the interference with Akt downstream effects would synergize with the antitumor activity of thalidomide.Key words: matrix metalloproteinases, thalidomide, B-cell malignancies, integrins. -mediated signaling pathways. Haematologica. 2010; 95:456-463. doi:10.3324/haematol.2009 Thalidomide decreases gelatinase production by malignant B lymphoid cell lines through disruption of multiple integrin-mediated signaling pathways Citation: Segarra M, Lozano E, Corbera-Bellalta M, Vilardell C, Cibeira M-T, Esparza J, Izco N, Bladé J, and Cid MC. Thalidomide decreases gelatinase production by malignant B lymphoid cell lines through disruption of multiple integrin

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Advances in therapy of multiple myeloma

Cited by 36 publications

References 53 publications

Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents

Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents

Lack of CD56 expression on myeloma cells is not a marker for poor prognosis in patients treated by high-dose chemotherapy and is associated with translocation t(11;14)

Thalidomide decreases gelatinase production by malignant B lymphoid cell lines through disruption of multiple integrin-mediated signaling pathways

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