Salvage second transplantation in relapsed multiple myeloma

Purpose Thalidomide-dexamethasone (THAL-DEX) is standard induction therapy for multiple myeloma (MM). Tandem melphalan-based transplantations have yielded superior results to single transplantations. Phase II trial S0204 was designed to improve survival results reported for the predecessor, phase III trial S9321 by 50%. Patients and Methods Newly diagnosed patients with MM were eligible for S0204 with THAL-DEX induction, tandem melphalan-based tandem transplantation, and THAL-prednisone maintenance. Results Of 143 eligible patients, 142 started induction, 73% completed first transplantation, 58% completed second transplantation, and 56% started maintenance. The quantity of stem cells required for two transplantations was reached in 88% of 111 patients undergoing collection, 74% of whom completed both transplantations. Partial response, very good partial remission, and complete response were documented after 12 months of maintenance therapy in 87%, 72%, and 22% of patients, respectively. During a median follow-up time of 37 months, 4-year estimates of event-free and overall survival were 50% and 64%, respectively. Survival outcomes were superior for International Staging System (ISS) stage 1 disease, when lactate dehydrogenase (LDH) levels were normal and a second transplantation was applied in a timely fashion. Conclusion Both overall survival (P = .0002) and event-free survival (P < .0001) were significantly improved with S0204 compared with S9321 when 121 and 363 patients, respectively, were matched on ISS stage and LDH.

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Assessment of the role of timing of second transplantation in multiple myeloma by multistate modeling

Experimental Hematology ◽

10.1016/j.exphem.2008.06.007 ◽

2008 ◽

Vol 36 (11) ◽

pp. 1567-1571 ◽

Cited By ~ 6

Author(s):

Simona Iacobelli ◽

Jane Apperley ◽

Curly Morris

Keyword(s):

Multiple Myeloma ◽

Second Transplantation

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Benefit and Timing of Second Transplantations in Multiple Myeloma: Clinical Findings and Methodological Limitations in a European Group for Blood and Marrow Transplantation Registry Study

Journal of Clinical Oncology ◽

10.1200/jco.2004.06.144 ◽

2004 ◽

Vol 22 (9) ◽

pp. 1674-1681 ◽

Cited By ~ 41

Author(s):

C. Morris ◽

S. Iacobelli ◽

R. Brand ◽

B. Bjorkstrand ◽

M. Drake ◽

...

Keyword(s):

Multiple Myeloma ◽

Marrow Transplantation ◽

Reference Group ◽

Autologous Transplantation ◽

Hazard Ratio ◽

Optimal Timing ◽

Blood And Marrow Transplantation ◽

Second Transplantation ◽

European Group ◽

Related Mortality

Purpose To use European Group for Blood and Marrow Transplantation registry data to assess the benefit and optimal timing of a double-autologous transplantation strategy for patients with myeloma. Patients and Methods 7,452 transplantation patients described as being either in a multiple graft program (“planned”) or not, were analyzed on an intention-to-treat basis. Subsequent multivariate analyses concentrated on the real occurrence of second transplantation, survival, relapse, and transplant-related mortality. Results Although the transplantation rate in the planned group failed to reach 60%, the median survival from transplantation is 60 months for the planned, compared with 51 months for the remainder group. While the hazard ratio of the planned group is 0.89 (95% CI, 0.79 to 1.00; P =.05) before approximately 70 months, this “effect” is reversed after 70 months, with the hazard ratio estimated as 3.01 (95% CI, 1.07 to 8.46; P = .04). A time-dependent multivariate Cox analysis shows that, taking patients without a second transplantation as a reference group, those receiving a second transplantation in first remission (ie, before relapse) show an increased probability of transplant-related mortality, especially if the transplantation is performed more than 12 months after the first, and the reduction of the risk of relapse is less than when the transplantation is performed earlier. Performing a second transplantation after relapse does not seem to prolong survival, though a second transplantation before relapse is associated with a higher probability of mortality. Conclusion To improve survival of tandem autologous transplantation in multiple myeloma, the second transplantation should preferably be performed before relapse and within 6 to 12 months of the first transplantation.

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Refractory Evans Syndrome after Autologous Stem Cell Transplantation for Multiple Myeloma: Management with a Second Transplantation

Internal Medicine ◽

10.2169/internalmedicine.49.2922 ◽

2010 ◽

Vol 49 (7) ◽

pp. 683-687 ◽

Cited By ~ 2

Author(s):

Dai Chihara ◽

Takashi Sakamoto ◽

Kazue Arimoto-Miyamoto ◽

Wataru Kishimoto ◽

Tomoharu Takeoka ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Evans Syndrome ◽

Second Transplantation

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Proteasome inhibitors as therapeutics

Essays in Biochemistry ◽

10.1042/bse0410205 ◽

2005 ◽

Vol 41 ◽

pp. 205-218

Author(s):

Constantine S. Mitsiades ◽

Nicholas Mitsiades ◽

Teru Hideshima ◽

Paul G. Richardson ◽

Kenneth C. Anderson

Keyword(s):

Multiple Myeloma ◽

Drug Class ◽

Proteasome Inhibitors ◽

Cell Cycle Regulators ◽

Current State ◽

Intracellular Mechanism ◽

Ubiquitin Proteasome ◽

Proteasome Pathway ◽

Hodgkin's Lymphomas ◽

Clinical Research Data

The ubiquitin–proteasome pathway is a principle intracellular mechanism for controlled protein degradation and has recently emerged as an attractive target for anticancer therapies, because of the pleiotropic cell-cycle regulators and modulators of apoptosis that are controlled by proteasome function. In this chapter, we review the current state of the field of proteasome inhibitors and their prototypic member, bortezomib, which was recently approved by the U.S. Food and Drug Administration for the treatment of advanced multiple myeloma. Particular emphasis is placed on the pre-clinical research data that became the basis for eventual clinical applications of proteasome inhibitors, an overview of the clinical development of this exciting drug class in multiple myeloma, and a appraisal of possible uses in other haematological malignancies, such non-Hodgkin's lymphomas.

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