Minimal Residual Disease (MRD) Assessment before and after Autologous Hematopoietic Cell Transplantation (AutoHCT) and Maintenance for Multiple Myeloma (MM): Results of the Prognostic Immunophenotyping for Myeloma Response (PRIMeR) Study

Hahn, Theresa; Wallace, Paul K.; Fraser, Raphael; Fei, Mingwei; Tario, Joseph D.; Howard, Alan; Zhang, Yali; Blackwell, Beth; Brunstein, Claudio G.; Efebera, Yvonne A.; Geller, Nancy L.; Giralt, Sergío; Hari, Parameswaran; Knust, Kristin; Koreth, John; Krishnan, Amrita; Landau, Heather; Shah, Nina; Stadtmauer, Edward A.; Vogl, Dan T.; McCarthy, Philip L.; Pasquini, Marcelo C.

doi:10.1016/j.bbmt.2018.12.687

Cited by 23 publications

(21 citation statements)

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“…Such studies are already underway in multiple myeloma . Similar to our report, studies assessing MRD in multiple myeloma clinical trials have also included patients in less than complete hematologic response . There were two MRD negative patients in our cohort who were not in CR or VGPR.…”

Section: Discussionsupporting

confidence: 60%

“…While they may have been truly MRD negative, it is also possible that these patients were false negative as bone marrow plasma cell involvement can be variable and sampling heterogeneity may result in false negative results. Similar findings have been seen in multiple myeloma . These patients were excluded from survival analysis to ensure uniformity.…”

Section: Discussionmentioning

confidence: 65%

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Impact of minimal residual negativity using next generation flow cytometry on outcomes in light chain amyloidosis

et al. 2020

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We evaluated bone marrow minimal residual disease (MRD) negativity in 44 patients with light chain (AL) amyloidosis using next generation flow cytometry (sensitivity ≥1 × 10 −5 ; median events analyzed: 8.7 million, range: 4.8 to 9.7 million). All patients underwent MRD testing in 2 years from start of therapy (median: 7 months). The overall MRD negative rate was 64% (n = 28). The MRD-negative rate after one-line of therapy was 71% (20/28). And, MRD negative rates were higher with stem-cell transplant as first-line therapy (86%, 18/21) vs chemotherapy alone as first-line treatment (29%, 2/7), P = .005. The MRD negative rate amongst patients in complete response was 75% (15/20), and in very good partial response, 50% (11/22). There were two patients in partial response/rising light chains (with renal dysfunction) who

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 65%

Impact of minimal residual negativity using next generation flow cytometry on outcomes in light chain amyloidosis

et al. 2020

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“…On the other hand, Hahn et al demonstrated in a transplant-eligible population that patients who were MRD-negative pre-ASCT, pre-maintenance, and 1-year post-ASCT showed all a better PFS compared to MRD-positive patients. Only the 1-year post-ASCT timepoint was associated with better OS (3-year post-ASCT OS 96 vs. 66% for MRDnegative vs. MRD-positive patients) (53). These data suggest that the duration of MRD negativity may be important, but little data are available on sustained MRD negativity (i.e., the need to confirm MRD at different timepoints) and on its optimal duration.…”

Section: Mrd Results In the Clinical Setting: Relevant Questionsmentioning

confidence: 93%

“…Data clearly show that, as we continue to intensify patient treatment, the percentage of MRD-negative patients increases (39,43,53,55,56) and even maintenance treatment can convert a significant percentage of MRD-positive patients into MRDnegative [e.g., 27-30% with lenalidomide maintenance in a pooled analysis (9,46)]. Each timepoint can be important due to different clinical reasons.…”

Section: Mrd Results In the Clinical Setting: Relevant Questionsmentioning

confidence: 99%

Clinical Applications and Future Directions of Minimal Residual Disease Testing in Multiple Myeloma

et al. 2020

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In the last years, the life expectancy of multiple myeloma (MM) patients has substantially improved thanks to the availability of many new drugs. Our ability to induce deep responses has improved as well, and the treatment goal in patients tolerating treatment moved from the delay of progression to the induction of the deepest possible response. As a result of these advances, a great scientific effort has been made to redefine response monitoring, resulting in the development and validation of high-sensitivity techniques to detect minimal residual disease (MRD). In 2016, the International Myeloma Working Group (IMWG) updated MM response categories defining MRD-negative responses both in the bone marrow (assessed by next-generation flow cytometry or next-generation sequencing) and outside the bone marrow. MRD is an important factor independently predicting prognosis during MM treatment. Moreover, using novel combination therapies, MRD-negative status can be achieved in a fairly high percentage of patients. However, many questions regarding the clinical use of MRD status remain unanswered. MRD monitoring can guide treatment intensity, although well-designed clinical trials are needed to demonstrate this potential. This mini-review will focus on currently available techniques and data on MRD testing and their potential future applications.

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“…However, this effect was mitigated in patients receiving further treatment after ASCT. Indeed, it should be noted that ASCT, consolidation and maintenance, especially with drugs not used during induction, still have the potential to eradicate MRD in a substantial number of patients who are MRD-positive at post-induction time point [7,8,43,70,123].…”

Section: Future Perspectivesmentioning

confidence: 99%

Pursuing a Curative Approach in Multiple Myeloma: A Review of New Therapeutic Strategies

D’Agostino

Bertamini

Oliva

et al. 2019

Cancers

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Multiple myeloma (MM) is still considered an incurable hematologic cancer and, in the last decades, the treatment goal has been to obtain a long-lasting disease control. However, the recent availability of new effective drugs has led to unprecedented high-quality responses and prolonged progression-free survival and overall survival. The improvement of response rates has prompted the development of new, very sensitive methods to measure residual disease, even when monoclonal components become undetectable in patients' serum and urine. Several scientific efforts have been made to develop reliable and validated techniques to measure minimal residual disease (MRD), both within and outside the bone marrow. With the newest multidrug combinations, a good proportion of MM patients can achieve MRD negativity. Long-lasting MRD negativity may prove to be a marker of "operational cure", although the follow-up of the currently ongoing studies is still too short to draw conclusions. In this article, we focus on results obtained with new-generation multidrug combinations in the treatment of high-risk smoldering MM and newly diagnosed MM, including the potential role of MRD and MRD-driven treatment strategies in clinical trials, in order to optimize and individualize treatment.

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Minimal Residual Disease (MRD) Assessment before and after Autologous Hematopoietic Cell Transplantation (AutoHCT) and Maintenance for Multiple Myeloma (MM): Results of the Prognostic Immunophenotyping for Myeloma Response (PRIMeR) Study

Cited by 23 publications

References 0 publications

Impact of minimal residual negativity using next generation flow cytometry on outcomes in light chain amyloidosis

Impact of minimal residual negativity using next generation flow cytometry on outcomes in light chain amyloidosis

Clinical Applications and Future Directions of Minimal Residual Disease Testing in Multiple Myeloma

Pursuing a Curative Approach in Multiple Myeloma: A Review of New Therapeutic Strategies

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