Molecular remission after myeloablative allogeneic stem cell transplantation predicts a better relapse-free survival in patients with multiple myeloma

Corradini, Paolo; Cavo, Michèle; Lokhorst, Henk M.; Martinelli, Giovanni; Terragna, Carolina; Majolino, Ignazio; Valagussa, Pinuccia; Boccadoro, Mario; Samson, Diana; Bacigalupo, Andrea; Russell, Nigel H.; Montefusco, Vittorio; Voena, Claudia; Gahrton, Gösta

doi:10.1182/blood-2003-01-0189

Cited by 174 publications

(120 citation statements)

References 24 publications

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“…Corradini et al demonstrated that a molecular remission achieved after myeloablative conditioning, as determined by polymerase chain reaction for immunoglobulin gene rearrangements generating a clone-specific molecular marker, was associated with possible cure, whereas patients with persistent minimal residual disease were destined to develop disease recurrence. 36 Similar results were seen in the RIC setting as well. 18 Patients who develop disease recurrence after SCT may respond to donor lymphocyte infusion (DLI).…”

Section: Discussionsupporting

confidence: 71%

Allogenic hematopoietic stem‐cell transplantation with reduced‐intensity conditioning in patients with refractory and recurrent multiple myeloma

Shimoni

Hardan

Ayuk

et al. 2010

Cancer

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BACKGROUND: Allogeneic stem cell transplantation (SCT) with myeloablative conditioning is potentially curative therapy for myeloma, but is reportedly associated with a high risk of nonrecurrence mortality (NRM). Reduced-intensity conditioning (RIC) allows for the reduction of NRM, but the recurrence rate is increased. The role and timing of allogeneic SCT in the disease course remains controversial. To the authors' knowledge, there are limited data regarding the long-term outcome of RIC in the recurrent/refractory setting. METHODS: A retrospective analysis was conducted of SCT outcomes in 50 patients who received RIC for recurrent/refractory myeloma between the years 2001 and 2004. All patients were given fludarabine-melphalan based conditioning and stem cell grafts from a related (n ¼ 27) or unrelated donor (n ¼ 23). RESULTS: The median age was 53 years. Forty-seven patients failed a prior autologous SCT. Thirty patients were in disease remission at the time of SCT and 20 had stable or progressive disease. With a median follow-up of 6.4 years (range, 5-7.9 years), the overall and progression-free survival (PFS) rates were 34% and 26%, respectively. The NRM rate was 26%. Adverse prognostic factors for survival included SCT not in remission, long duration of disease (>5 years from diagnosis), and transplantation from a female donor to a male recipient. The 7-year PFS in 19 patients with none of these adverse prognostic factors was 47%. Chronic graft versus host disease and the achievement of complete remission after SCT were associated with improved outcome. CONCLUSIONS: Allogeneic SCT can result in long-term PFS in a subset of myeloma patients who fail prior therapy and should be considered early after failure and after achieving remission. Cancer 2010;116;3621-30.

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Section: Discussionsupporting

confidence: 71%

Allogenic hematopoietic stem‐cell transplantation with reduced‐intensity conditioning in patients with refractory and recurrent multiple myeloma

Shimoni

Hardan

Ayuk

et al. 2010

Cancer

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“…84,85 This level has been achieved almost exclusively in the context of allogeneic stem cell transplantation in a very small subset of patients. However, in the near future, molecular remissions might be achieved in more patients with the combination of HDT and novel agents.…”

Section: Which Level Of Response Is Necessary?mentioning

confidence: 99%

The role of complete response in multiple myeloma

Harousseau

Attal

Avet-Loiseau

2009

Blood

208

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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“…Although the same has been shown in the setting of autologous transplantation, [32][33][34] the meaning of CR in the allogeneic transplantation setting is distinct since the ultimate goal is longterm cure. This is underlined by data showing the prognostic Allogeneic transplantation in multiple myeloma S Gerull et al significance of reaching molecular remission, 35,36 and suggests that molecular monitoring should be considered after allogeneic transplantation. The role of allogeneic transplantation in the era of novel agents has been a subject of growing debate.…”

Section: Discussionmentioning

confidence: 99%

Allo-SCT for multiple myeloma in the era of novel agents: a retrospective study on behalf of Swiss Blood SCT

Gerull

Stangel

Aissa

et al. 2012

Bone Marrow Transplant

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Despite the introduction of novel drugs, cure of multiple myeloma remains rare. Allo-SCT can induce long-term remission, but randomized studies in advanced disease are lacking and the influence of novel drugs remains unclear. In our retrospective analysis of all patients with myeloma allografted in Switzerland, 95 patients were transplanted between 1988 and 2011. Most patients were heavily pre-treated, and 53% received novel drugs before transplant. In all, 51% were allografted after relapse or progression. Transplant trends changed over time with an increase in reduced intensity conditioning and unrelated donors. At the time of analysis 47 patients remained alive, with a median follow-up of survivors of 53 months. Acute GVHD II-IV and chronic GVHD (cGVHD) occurred in 49% and 53%, respectively; TRM at 5 years was 18%. Five-year OS and PFS were 51% and 29%, respectively. Patients who received transplant upfront vs after relapse had a significantly better outcome, as well as those who had a related donor and achieved CR post transplant. We found no impact of pre-treatment with novel drugs or cGVHD. Although long-term remission following allo-SCT can be achieved, GVHD and TRM remain major limitations. Our series suggests that benefit is highest when allo-SCT is used early in the disease.

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Molecular remission after myeloablative allogeneic stem cell transplantation predicts a better relapse-free survival in patients with multiple myeloma

Cited by 174 publications

References 24 publications

Allogenic hematopoietic stem‐cell transplantation with reduced‐intensity conditioning in patients with refractory and recurrent multiple myeloma

Allogenic hematopoietic stem‐cell transplantation with reduced‐intensity conditioning in patients with refractory and recurrent multiple myeloma

The role of complete response in multiple myeloma

Allo-SCT for multiple myeloma in the era of novel agents: a retrospective study on behalf of Swiss Blood SCT

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