Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: Preliminary Results of an IFM Phase II Study

Harousseau, Jean‐Luc; Attal, Michel; Coiteux, Valérie; Stoppa, Anne‐Marie; Hulin, Cyrille; Benboubker, Lotfi; Fuzibet, J. G.; Renaud, Marc

doi:10.1200/jco.2005.23.16_suppl.6653

Cited by 159 publications

(218 citation statements)

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“…13 These results for BTD and the response rates observed in our analysis similarly appear greater than those reported with thalidomide plus dexamethasone in 2 phase 3 studies in frontline MM. 5,6 Furthermore, the response rates reported with BTD in the current analysis and in the GIMEMA phase 3 study also appear to compare favorably with those reported for bortezomib plus dexamethasone [36][37][38][39] ; for example, in the French Myeloma Intergroup (IFM) phase 3 study of bortezomib plus dexamethasone versus VAD as induction therapy, the response rate to bortezomib plus dexamethasone induction was 82%, including a 39% !VGPR rate and a 15% CR/near-CR rate, with 68% achieving a !VGPR after transplantation, including a 39% CR/near-CR rate 38 The approach of combining bortezomib with an immunomodulatory drug and dexamethasone as induction therapy in newly diagnosed patients with MM also has been demonstrated in 2 studies of the combination of bortezomib, the thalidomide analog lenalidomide, and dexamethasone. 40,41 Preliminary results from a phase 1/2 study indicate highly promising activity with this combination, which produced a 100% overall response rate, including a 75% !VGPR rate and a 40% CR/near-CR rate.…”

Section: Original Article 3148mentioning

confidence: 55%

Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma

Kaufman

Nooka

Vrana³

et al. 2010

Cancer

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BACKGROUND: This single-center retrospective study determined the efficacy of bortezomib, thalidomide, and dexamethasone (BTD) as induction for patients with multiple myeloma (MM) who were eligible for autologous stem cell transplantation (ASCT). METHODS: Patients with symptomatic MM who had received BTD induction before stem cell collection at Winship Cancer Institute were included. BTD induction comprised up to 8 3-week cycles of bortezomib 1.3 mg/m 2 on Days 1, 4, 8, and 11; thalidomide 100 mg daily; and dexamethasone 40 mg on Days 1 through 4 and Days 9 through 12. Stem cell mobilization involved granulocyte-colony-stimulating factor and/or cyclophosphamide. Response was assessed according to European Group for Blood and Marrow Transplantation criteria. RESULTS: Review of medical records identified 44 eligible patients (34 patients who were treated in the front-line setting and 10 patients who were treated for recurrent disease) who received a median of 4 BTD cycles. The overall response rate (ORR) was 91%, which included a greater than or equal to very good partial response (!VGPR) rate of 57% (including 20% stringent complete responses/complete response [sCR/CR] rate). In front-line patients, the ORR was 94%, which included a 56% !VGPR rate (24% sCR/CR). The median CD34-positive stem cell collection was 10.67 Â 10 6 /kg. The ORR after ASCT in 34 patients who were evaluable for response was 100%, including a 76% !VGPR rate (53% sCR/CR). Among all 44 patients, the median progression-free survival (PFS) was 27.4 months. The median overall survival (OS) was not reached after a median follow-up of 25 months, and the 2-year OS rate was 82%. There were no significant differences in PFS (27.4 months vs 23.5 months) or in 2-year survival (80% vs 90%) between patients who did and did not undergo ASCT, respectively. Twenty patients (45%) developed neuropathy, including 4 (9%) with grade 3 neuropathy episodes, and 1 patient developed deep vein thrombosis. CONCLUSIONS: BTD was highly effective and well tolerated as induction for MM patients who were eligible for ASCT. Long-term outcomes appeared to be similar with or without ASCT consolidation. Cancer 2010;116:3143-51.

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Section: Original Article 3148mentioning

confidence: 55%

Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma

Kaufman

Nooka

Vrana³

et al. 2010

Cancer

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“…63,64 Bortezomib-based therapy is also associated with rapid responses typically occurring within the first two cycles of treatment. [60][61][62] In the SUMMIT and CREST trials, bortezomib treatment was found to lead to an overall response rate of 25 and 30% in patients with moderate and severe renal impairment, respectively, 65 whereas the toxicity was comparable to that of patients without renal impairment. In a subanalysis of the APEX trial, bortezomib was effective in patients with renal impairment, including those with severe renal impairment, 66 with response rates and time to response similar across all subgroups of patients with varying degrees of renal function.…”

Section: Bortezomibmentioning

confidence: 99%

“…[60][61][62] The pharmacokinetics of bortezomib are independent of renal clearance and are not influenced by the degree of renal impairment; dose adjustments are not required for patients with renal insufficiency, but in patients undergoing dialysis, bortezomib should be administered after dialysis. Adverse events in patients undergoing dialysis are largely similar to those observed in controls and in those with mild-to-severe impairment, with the exception of renal and metabolic adverse events, which were found to be more common in patients undergoing dialysis.…”

Section: Bortezomibmentioning

confidence: 99%

Pathogenesis and treatment of renal failure in multiple myeloma

et al. 2008

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Renal failure is a frequent complication in patients with multiple myeloma (MM) that causes significant morbidity. In the majority of cases, renal impairment is caused by the accumulation and precipitation of light chains, which form casts in the distal tubules, resulting in renal obstruction. In addition, myeloma light chains are also directly toxic on proximal renal tubules, further adding to renal dysfunction. Adequate hydration, correction of hypercalcemia and hyperuricemia and antimyeloma therapy should be initiated promptly. Recovery of renal function has been reported in a significant proportion of patients treated with conventional chemotherapy, especially when high-dose dexamethasone is also used. Severe renal impairment and large amount of proteinuria are associated with a lower probability of renal recovery. Novel agents, such as thalidomide, bortezomib and lenalidomide, have significant activity in pretreated and untreated MM patients. Although there is limited experience with thalidomide and lenalidomide in patients with renal failure, data suggest that bortezomib may be beneficial in this population. Clinical studies that have included newly diagnosed and refractory patients indicate that bortezomib-based regimens may result in rapid reversal of renal failure in up to 50% of patients and that full doses of bortezomib can be administered without additional toxicity.

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“…More recently, clinical trials incorporating novel therapies such as thalidomide and its analogs and the proteasome inhibitor bortezomib continue to redefine the role of auto-SCT in this new era. [11][12][13][14] Early auto-SCT in patients with myeloma have typically resulted in median progression free survival of 2-3 years and overall survival of 4-5 years in randomized trials. [5][6][7] Various risk factors have been shown to identify patients with short survival after an auto-SCT, most importantly high risk genetic features.…”

Section: Introductionmentioning

confidence: 99%

Impact of early relapse after auto-SCT for multiple myeloma

Kumar

Mahmood

Lacy

et al. 2008

Bone Marrow Transplant

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Auto-SCT is an effective therapy for patients with multiple myeloma (MM), but nearly a fifth of these patients relapse within a year of auto-SCT. We studied 494 patients, undergoing auto-SCT within 12 months of diagnosis of MM. Patients were divided into two groups: early relapse (relapse p12 months from auto-SCT) and late relapse (either relapsed 412 months after auto-SCT or disease free at the last follow up). One hundred twenty patients (24%) were in the early relapse and 374 (76%) were in the late-relapse groups. The early relapse group had a significantly shorter median overall survival (OS) from diagnosis (26.6 vs 90.7 months; Po0.001) and from auto-SCT (20.1 vs 82.5 months; Po0.001). Among the 345 patients who have relapsed after auto-SCT, median OS from relapse was 10.8 months in the early relapse group compared to 41.8 months for the rest (Po0.001) and was longer with increasing duration of response to the SCT. In multivariate analyses, labeling index X1% at transplant, greater than one treatment regimen prior to auto-SCT, and failure to achieve a complete response were predictive of early relapse. Patients who relapse within 12 months of an auto-SCT have a poor outcome and should be offered trials evaluating novel treatment approaches.

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Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: Preliminary Results of an IFM Phase II Study

Cited by 159 publications

References 0 publications

Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma

Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma

Pathogenesis and treatment of renal failure in multiple myeloma

Impact of early relapse after auto-SCT for multiple myeloma

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