Making progress in treating multiple myeloma with total therapies: issue of complete remission and more

Barlogie, Bart; Rhee, Frits van; Shaughnessy, John D.; Anaissie, Elias; Crowley, John

doi:10.1038/leu.2008.40

Cited by 21 publications

(16 citation statements)

References 18 publications

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“…Damien Roos-Weil, 1 Philippe Moreau, 2 Hervé Avet-Loiseau, 3 Jean-Louis Golmard, 4 Mathieu Kuentz, 5 Stéphane Vigouroux, 6 Gérard Socié, 7 Sabine Furst, 8 Jean Soulier, 9 Steven Le Gouill, 2 Sylvie François, 10 Anne Thiebaut, 11 Agnès Buzyn, 12 Natacha Maillard, 13 Ibrahim Yakoub-Agha, 14 Nicole Raus, 15 Jean-Paul Fermand, 16 Mauricette Michallet, 17 Didier Blaise, 8 and Nathalie Dhédin 1 for the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)…”

Section: Impact Of Genetic Abnormalities After Allogeneic Stem Cell Tunclassified

“…It has even been suggested that the use of these novel agents could overcome the negative impact of del(13q) and t(4;14); however, these agents do not seem to provide an advantage to patients with del(17p) who still exhibit the worse outcomes. [7][8][9][10][11][12] The role of allogeneic stem cell transplantation (allo-SCT) in MM remains a matter of controversy. To better evaluate its benefits as first-line therapy, seven prospective studies have been conducted or are currently ongoing comparing single or double auto-SCT to a tandem approach, defined as reduced intensity conditioning (RIC) transplants following a first auto-SCT.…”

Section: Introductionmentioning

confidence: 99%

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Impact of genetic abnormalities after allogeneic stem cell transplantation in multiple myeloma: a report of the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire

Roos‐Weil¹,

Moreau²,

Avet‐Loiseau³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundThe impact of cytogenetic abnormalities in multiple myeloma after allogeneic stem cell transplantation has not been clearly defined. This study examines whether allogeneic stem cell transplantation could be of benefit for myeloma patients with high-risk cytogenetic abnormalities. Design and MethodsThis is a retrospective multicenter analysis of the registry of the Société Française de Greffe de Moelle et de Thérapie Cellulaire, including 143 myeloma patients transplanted between 1999 and 2008. ResultsThe incidences of cytogenetic abnormalities were 59% for del(13q), 25% for t(4;14), 25% for del(17p) and 4% for t(14;16). When comparing the population carrying an abnormality to that without the same abnormality, no significant difference was found in progression-free survival, overall survival or progression rate. Patients were grouped according to the presence of any of the poor prognosis cytogenetic abnormalities t(4;14), del(17p) or t(14;16) (n=53) or their absence (n=32). No difference in outcomes was observed between these two groups: the 3-year progression-free survival, overall survival and progression rates were 30% versus 17% (P=0.9), 45% versus 39% (P=0.8) and 53% versus 75% (P=0.9), respectively. ConclusionsThese data indicate that allogeneic stem cell transplantation could potentially be of benefit to high-risk myeloma patients.Key words: multiple myeloma, cytogenetic abnormalities, allogeneic transplantation. Kuentz M, Vigouroux S, Socié G, Furst S, Soulier J, Le Gouill S, François S, Thiebaut A, Buzyn A, Maillard N, Yakoub-Agha I, Raus N, Fermand J-P, Michallet M, Blaise D, and Dhédin N

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Section: Impact Of Genetic Abnormalities After Allogeneic Stem Cell Tunclassified

Section: Introductionmentioning

confidence: 99%

Impact of genetic abnormalities after allogeneic stem cell transplantation in multiple myeloma: a report of the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire

Roos‐Weil¹,

Moreau²,

Avet‐Loiseau³

et al. 2011

Haematologica

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“…20 Analysis of the intensive programs at Arkansas University suggested that stringently defined CR was critical for EFS and OS only in a small subgroup of patients with poor prognosis, as defined by gene expression profiling. 63,64 These findings could mean that in more aggressive MMs, which are Summary of largest studies (Ͼ 100 patients). EFS indicates event-free survival; PFS, progression-free survival; OS, overall survival; ASCT, autologous stem cell transplantation; R, retrospective; CR, complete response; P, prospective; VGPR, very good partial response; PR, partial response; n-CR, near complete response; and NA, not available.…”

Section: The Impact Of Cr Depends On the Age Of Patientsmentioning

confidence: 99%

The role of complete response in multiple myeloma

Harousseau

Attal

Avet-Loiseau

2009

Blood

209

148

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In multiple myeloma (MM), the impact of complete response (CR) could be shown only after introduction of high-dose therapy plus autologous stem cell transplantation (ASCT). In the context of ASCT, achieving CR (negative immunofixation and normal bone marrow) or at least very good partial response is associated with longer progression-free survival and in most studies longer survival. With novel agents, high CR rates are achieved and this prognostic impact of CR is being shown as well, both in relapsed and in newly diagnosed MM. However the benefit of CR achievement depends on the type of treatment and is not identical for all patients. In elderly patients, treatments inducing more CR may be more toxic. Although CR achievement is necessary in patients with poor-risk disease, it might not be as critical for long survival in more indolent MM. CR achievement is not the only objective of treatment because it is possible to further improve the depth of response and the outcome by continuing treatment after CR achievement. Finally, there are several levels of CR and in the future it will be necessary to confirm the prognostic impact of immunophenotypic or molecular CR or of CR defined by imaging procedures. (Blood. 2009;114: 3139-3146)

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“…MM remains an incurable disease (median overall survival, 4.4-7.1 y) despite the recent availability of new agents that, especially when used in combination regimens, have dramatically improved initial response rates (1)(2)(3). Therefore, new approaches that induce long-term tumor regression and improve disease outcome are needed and urgently sought for.…”

mentioning

confidence: 99%

Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors

Weers

Tai

Veer

et al. 2011

The Journal of Immunology

873

679

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CD38, a type II transmembrane glycoprotein highly expressed in hematological malignancies including multiple myeloma (MM), represents a promising target for mAb-based immunotherapy. In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in patient MM cells, both with autologous and allogeneic effector cells. Daratumumab stood out from other CD38 mAbs in its strong ability to induce complement-dependent cytotoxicity in patient MM cells. Importantly, daratumumab-induced Ab-dependent cellular cytotoxicity and complement-dependent cytotoxicity were not affected by the presence of bone marrow stromal cells, indicating that daratumumab can effectively kill MM tumor cells in a tumor-preserving bone marrow microenvironment. In vivo, daratumumab was highly active and interrupted xenograft tumor growth at low dosing. Collectively, our results show the versatility of daratumumab to effectively kill CD38-expressing tumor cells, including patient MM cells, via diverse cytotoxic mechanisms. These findings support clinical development of daratumumab for the treatment of CD38-positive MM tumors.

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Making progress in treating multiple myeloma with total therapies: issue of complete remission and more

Cited by 21 publications

References 18 publications

Impact of genetic abnormalities after allogeneic stem cell transplantation in multiple myeloma: a report of the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire

Impact of genetic abnormalities after allogeneic stem cell transplantation in multiple myeloma: a report of the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire

The role of complete response in multiple myeloma

Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors

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