Early versus delayed autologous stem cell transplant in patients receiving novel therapies for multiple myeloma

Dunavin, Neil; Wei, Lai; Elder, Patrick; Phillips, Gary; Benson, Don M.; Hofmeister, Craig C.; Penza, Sam; Greenfield, Carli N; Rose, Karen; Rieser, Gisele; Merritt, Lisa; Ketcham, J.; Heerema, Nyla A.; Byrd, John C.; Devine, Steven M.; Efebera, Yvonne A.

doi:10.3109/10428194.2012.751528

Cited by 64 publications

(31 citation statements)

References 26 publications

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“…17,29,30 Given the striking efficacy of RVD [with overall response rates of 100% and near complete or complete remission (CR) rates of 52% seen in phase 2 populations] and the remarkable results of CRD, with 63% near CR or better reported, randomized studies incorporating both proteasome inhibition and prolonged maintenance are obviously key. 18,31…”

Section: Best Induction Regimens In the Novel Agent Era With The Intementioning

confidence: 99%

Early or delayed transplantation for multiple myeloma in the era of novel therapy: does one size fit all?

et al. 2014

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For the last 20 years, high-dose therapy with autologous stem cell transplantation (ASCT) for multiple myeloma has been considered a standard frontline treatment for younger patients with adequate organ function. With the introduction of novel agents, specifically thalidomide, bortezomib, and lenalidomide, the role of ASCT has changed in several ways. First, novel agents have been incorporated successfully as induction regimens, increasing the response rate before ASCT, and are now being used as part of both consolidation and maintenance with the goal of extending progression-free and overall survival. These approaches have shown considerable promise with significant improvements in outcome. Furthermore, the efficacy of novel therapeutics has also led to the investigation of these agents upfront without the immediate application of ASCT, and compelling preliminary results have been reported. Next-generation novel agents and the use of monoclonal antibodies have raised the possibility of not only successful salvage strategies to facilitate delayed transplantation for younger patients, but also the prospect of an nontransplantation approach achieving the same outcome. Moreover, this could be achieved without incurring acute toxicity or long-term complications that are inherent to high-dose alkylation, and melphalan exposure in particular. At present, the role of ASCT has therefore become an area of debate: should it be used upfront in all eligible patients, or should it be used as a salvage treatment at the time of progression for patients achieving a high quality of response with initial therapy? There is a clear need to derive a consensus that is useful for clinicians considering both protocol-directed and non-protocol-directed options for their patients. Participation in ongoing prospective randomized trials is considered vital. While preliminary randomized data from studies in Europe favor early ASCT with novel agents, differences in both agents and the combinations used, as well as limited information on overall survival and benefit for specific patient subsets, suggest that one size does not fit all. Specifically, the optimal approach to treatment of younger patients eligible for ASCT remains a key area for further research. A rigid approach to its use outside of a clinical study is difficult to justify and participation in prospective studies should be a priority. Learning Objective• To understand that research into the timing and role of ASCT is essential because the impact of both first-generation and second-generation novel agents, as well as other immunotherapeutic strategies including monoclonal antibodies, continue to improve patient outcome in MM

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Section: Best Induction Regimens In the Novel Agent Era With The Intementioning

confidence: 99%

Early or delayed transplantation for multiple myeloma in the era of novel therapy: does one size fit all?

et al. 2014

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“…One study reported the outcomes of 290 patients treated with IMiDs based therapy (thalidomide or lenalidomide) and that received early (within 12 mo of diagnosis) or late ASCT; PFS was similar irrespective of when ASCT was performed (early or late) and no significant difference could be observed in OS, with both groups experiencing a 4-year OS of 73% [48] . In a similar study Dunavin et al [47] retrospectively reviewed the outcome of 167 patients treated with novel agent-based therapy (IMiDs or PI) and receiving early or delayed ASCT. The 5-year OS from diagnosis was similar in the two groups (63% both in early and late ASCT, P = 0.45), in accordance with the data reported by Kumar et al [48] .…”

Section: Orr (%) Pfs (Mo) Os (Mo)mentioning

confidence: 99%

“…Cook et al [49] 2011 106 Retrospective 19 mo (relapse from first transplant) Yes 63% NR 37 Jimenez-Zepeda et al [51] [45] 2013 187 Retrospective 32 mo Yes 68% 5% at 5 yr 29% at 5 yr Shah et al [68] Brioli A. ASCT in MM in some cases given as a salvage treatment after a previous ASCT [44][45][46] , whilst in others patients received ASCT after relapsing from a treatment not including transplantation [29,47,48] . One of the biggest records is the one published by Sellner et al [44] , in which 200 MM patients retreated with ASCT at the time of relapse were retrospectively analysed.…”

Section: Orr (%) Pfs (Mo) Os (Mo)mentioning

confidence: 99%

“…Although median event free survival was longer for patients treated with early ASCT (39 mo vs 13 mo) the median OS was not significantly different between the two groups (64.6 mo vs 64 mo, P = 0.92), and 90% of the patients randomised to the VMPC arm were able to receive the planned delayed ASCT at the time of relapse [25] . Several analyses, summarised in Table 3, have investigated the role of ASCT as a salvage therapy for MM [29,[44][45][46][47][48][49][50][51] . These works are not always comparable, due to the different nature of the works (both prospective and retrospective) and to the fact that ASCT was …”

Section: Delayed Transplantationmentioning

confidence: 99%

“…In the era of novel agents two studies have retrospective analysed the role of early vs delayed ASCT [47,48] and one study prospectively evaluated a second ASCT after relapse from a previous one [46] . One study reported the outcomes of 290 patients treated with IMiDs based therapy (thalidomide or lenalidomide) and that received early (within 12 mo of diagnosis) or late ASCT; PFS was similar irrespective of when ASCT was performed (early or late) and no significant difference could be observed in OS, with both groups experiencing a 4-year OS of 73% [48] .…”

Section: Orr (%) Pfs (Mo) Os (Mo)mentioning

confidence: 99%

See 2 more Smart Citations

First linevsdelayed transplantation in myeloma: Certainties and controversies

Brioli¹

2016

WJT

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Use of autologous hematopoietic cell transplantation as initial therapy in multiple myeloma and the impact of socio‐geo‐demographic factors in the era of novel agents

Al-Hamadani

Hashmi

2014

American J Hematol

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Very effective combination chemotherapy using novel agents has become available in multiple myeloma (MM). Its impact on the use of high‐dose chemotherapy and autologous hematopoietic stem cell transplantation (AHCT) as part of initial therapy is unknown. Using the National Cancer Data Base, we studied the rate of upfront AHCT use among 137,409 newly diagnosed MM patients from 1998 to 2010 in the United States and determined whether disparity exists among various sociodemographic as well as geographic subgroups. Overall, 12,378 (9.0%) patients received AHCT as part of initial treatment. The use of upfront AHCT increased steadily from 5.2% in 1998 to 12.1% in 2010 (trend test, P < 0.001), with no sign of plateau. This was seen across all socio‐geo‐demographic subgroups except among patients treated in the Northeast where the rate fell from 8.7% in 1998 to 6.6% in 2010. In multivariable analysis, patients with the following characteristics were the least likely to receive AHCT (odds ratio): year of diagnosis from 1998 to 2003 before the era of novel agents (0.67), older age (0.35), Black race (0.58), Hispanic ethnicity (0.78), low level of education or annual household income (0.55), residence in a metro area (0.66), no or unknown medical insurance (0.30), treatment at a community cancer center (0.16), and treatment facility located in the Northeast region (0.54). Even after the introduction of novel agents, the rate of upfront AHCT in MM continues to increase annually. Significant disparities exist dependent on demographic, social, and geographic factors. Am. J. Hematol. 89:825–830, 2014. © 2014 Wiley Periodicals, Inc.

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Early versus delayed autologous stem cell transplant in patients receiving novel therapies for multiple myeloma

Cited by 64 publications

References 26 publications

Early or delayed transplantation for multiple myeloma in the era of novel therapy: does one size fit all?

Early or delayed transplantation for multiple myeloma in the era of novel therapy: does one size fit all?

First linevsdelayed transplantation in myeloma: Certainties and controversies

Use of autologous hematopoietic cell transplantation as initial therapy in multiple myeloma and the impact of socio‐geo‐demographic factors in the era of novel agents

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