Minimal residual disease in myeloma by flow cytometry: independent prediction of survival benefit per log reduction

Rawstron, Andy C.; Gregory, Walter M.; Tute, Ruth M. de; Davies, Faith E.; Bell, Sue; Drayson, Mark T.; Cook, Gordon; Jackson, Graham; Morgan, Gareth J.; Child, J. A.; Owen, Roger G.

doi:10.1182/blood-2014-07-590166

Cited by 159 publications

(159 citation statements)

References 11 publications

(8 reference statements)

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“…The observation that the actual therapy given to reach a deep response does not matter-whereas the fact that the multiple myeloma patient has obtained a deep response matters (MRD 10 − 6 negativity) 9 -is very similar to observations done by the UK myeloma study group. 13,14 The second interest area involves response-based multiple myeloma therapy. As opposed to a fixed number of RVd cycles, Sherrod et al 10 discuss that the actual MRD status could potentially be used to identify patients who benefit from upfront ASCT as a response-deepening strategy.…”

mentioning

confidence: 99%

MRD-driven treatment paradigm for newly diagnosed transplant eligible multiple myeloma patients

Landgren

Giralt

2016

Bone Marrow Transplant

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Minimal residual disease (MRD) testing is increasingly important for the assessment of treatment response in patients diagnosed with multiple myeloma. In fact, MRD negativity is consistently associated with a better PFS and overall survival. [1][2][3][4][5][6][7][8][9] In this issue of the Journal, Sherrod et al. 10 publish a timely review article focusing on MRD testing after stem cell transplantation for patients with multiple myeloma. They review and discuss novel biochemical assays (including serum-free light-chain assays and heavy-chain/light-chain assays) as well as novel methods to measure MRD, including multi-parametric flow cytometry, PCR, next-generation sequencing and functional imaging modalities. They outline the main literature on this topic and highlight on the strengths and weaknesses of each of these assays and approaches. Furthermore, they address practical questions related to MRD testing after stem cell transplantation for patients with multiple myeloma. As part of their conclusion, they point out the clear need for International Myeloma Working Group response criteria to be revised and updated to include MRD.In the final part of their paper, Sherrod et al. 10 conclude that the treatment paradigm for multiple myeloma continues to evolve, and as the depth and duration of responses continue to improve, more sensitive measures of disease evaluation should be integrated into the response algorithm. As MRD research continues to develop, in their opinion, two clinical areas will be of particular interest with regard to the use of high-dose melphalan (HDM) therapy followed by autologous stem cell transplant (ASCT) in multiple myeloma.The first interest area involves the question of whether it is beneficial for multiple myeloma patients to move forward with upfront HDM-ASCT or if a delayed HDM-ASCT following a set number of therapeutic cycles is equally good or better. As pointed out by Sherrod et al. 10 the role of upfront versus delayed HDM-ASCT is being evaluated in the ongoing Intergroupe Francophone du Myélome (IFM)-Dana-Farber Cancer Institute (DCMI) study (NCT01208662), in which patient receive three cycles of RVd (lenalidomide, bortezomib and dexamethasone) combination therapy followed by upfront HDM-ASCT, followed by two additional cycles of RVd and lenalidomide maintenance versus an additional five cycles of RVd and lenalidomide maintenance with the option of a delayed HDM-ASCT at relapse. The duration of lenalidomide maintenance is restricted to 1 year in the IFM part of the study, whereas the DFCI part of the study uses lenalidomide maintenance until disease progression. At the 2015 American Society of Hematology (ASH) meeting in Orlando, Attal 11 presented the results from the IFM part of the study, showing that the average PFS was longer in the arm with three cycles of RVd combination therapy followed by upfront HDM-ASCT, followed by two additional cycles of RVd and 1 year of lenalidomide maintenance. In the upfront HDM-ASCT arm, 93% of patients underwent ASCT and five toxic deaths occu...

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confidence: 99%

MRD-driven treatment paradigm for newly diagnosed transplant eligible multiple myeloma patients

Landgren

Giralt

2016

Bone Marrow Transplant

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“…Measuring MRD by multi-parameter flow cytometry accurately predicts overall survival in patients who have achieved a complete response (Paiva et al, 2012;Rawstron et al, 2015) and represents an opportunity to vastly shorten the time required for trials of aggressive treatment to report. 18 F-flurodeoxyglucose positron emission tomography (PET) CT scanning is also a predictor of PFS and OS, both after induction (Bartel et al, 2009) and after ASCT (Zamagni et al, 2015).…”

Section: Trial Endpointsmentioning

confidence: 99%

Augmenting Autologous Stem Cell Transplantation to Improve Outcomes in Myeloma

Maybury

Cook

Pratt

et al. 2016

Biology of Blood and Marrow Transplantation

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SummaryConsolidation with high dose chemotherapy and autologous stem cell transplantation (ASCT) is the standard of care for transplant eligible patients with multiple myeloma, based on randomised trials showing improved progression free survival with autologous transplantation following combination chemotherapy induction. These trials were performed before novel agents were introduced, and subsequently combinations of immunomodulatory drugs (IMiDs) and proteasome inhibitors as induction therapy have significantly improved rates and depth of response. Ongoing randomised trials are testing whether conventional autologous transplantation continues to improve responses following novel agent induction. While these results are awaited, it is important to review strategies for improving outcomes following ASCT. Conditioning prior to ASCT with higher doses of melphalan, and combinations of melphalan with other agents, including radiopharmaceuticals have been explored. Tandem ASCT, consolidation and maintenance therapy following ASCT have been investigated in phase III trials. Experimental cellular therapies using ex vivo primed dendritic cells , ex vivo expanded autologous lymphocytes, KIR-mismatched allogeneic NK cells, and genetically modified T cells are also in phase I trials to augment ASCT. This review summarises these strategies and highlights the importance of exploring strategies to augment ASCT even in the era of novel agent induction.

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“…11 MRD combined with cytogenetics gives a better prediction of outcome than standard CR. 7 Therefore, MRD has now been incorporated into several clinical trials.…”

Section: Prognostic Factorsmentioning

confidence: 99%

“…Using MRD for response evaluation may give a better prediction of OS. 6,7 With multiparameter flow cytometry (FCM) or next generation sequencing (NGS) it is possible to detect a tumor load of 10 -5 ( Figure 1). 5,6,[8][9][10] This is clinically relevant since time to progression (TTP) in patients with MRD below 10 -5 is significantly better than in patients with MRD between 10 -5 to 10 -3 or above 10 -3 (80 vs. 48 vs. 27 months).…”

Section: Prognostic Factorsmentioning

confidence: 99%