Minimal residual disease negativity and lenalidomide maintenance therapy are associated with superior survival outcomes in multiple myeloma

Patel, Dilan; Gopalakrishnan, Ragisha; Engelhardt, Brian G.; McArthur, Evonne; Sengsayadeth, Salyka; Culos, Katie; Byrne, Michael; Goodman, Stacey; Savani, Bipin N.; Chinratanalab, Wichai; Jagasia, Madan; Mosse, Claudio A.; Cornell, Robert F.; Kassim, Adetola A.

doi:10.1038/s41409-020-0791-y

Cited by 8 publications

(4 citation statements)

References 45 publications

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“…In the same study, MRD negative relapse was reported in 7% of the population with more than half of these patients being early responders who achieved MRD negativity after induction therapy and much akin to their disease presentation at the time of initial diagnosis. 12 Current literature reports a variable rate of MRD negativity in HR MM, particularly in the subset of patient with (del)17p [39][40][41][42][43] . Prospective clinical trials of high-risk MM incorporating monoclonal antibodies with novel agents have reported CR rates of 2.1-59%.…”

Section: Discussionmentioning

confidence: 99%

Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma

et al. 2022

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Multiple myeloma (MM) patients frequently attain a bone marrow (BM) minimal residual disease (MRD) negativity status in response to treatment. We identified 568 patients who achieved BM MRD negativity following autologous stem cell transplantation (ASCT) and maintenance combination therapy with an immunomodulatory agent and a proteasome inhibitor. BM MRD was evaluated by next generation flow cytometry (sensitivity of 10-5 cells) at 3 to 6 months intervals. With a median follow up of 9.9 years from diagnosis (range, 0.4 - 30.9), 61% of patients maintained MRD negativity, while 39% experienced MRD conversion at a median of 6.3 years (range, 1.4 - 25). The highest risk of MRD conversion occurred within the first 5 years after treatment and was observed more often in patients with abnormal metaphase cytogenetic abnormalities (95%vs. 84%; P = 0.001). MRD conversion was associated with a high risk of relapse and preceded it by a median of 1.0 year (range, 0 - 4.9). However, 27% of MRD conversion positive patients had not yet experienced a clinical relapse with a median follow-up of 9.3 years (range, 2.2 - 21.2). Landmark analyses using time from ASCT revealed patients with MRD conversion during the first 3 years had an inferior overall and progression-free survival compared to patients with sustained MRD negativity. MRD conversion correctly predicted relapse in 70%, demonstrating the utility of serial BM MRD assessment to complement standard laboratory and imaging to make informed salvage therapy decisions.

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Section: Discussionmentioning

confidence: 99%

Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma

et al. 2022

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“…We speculate that for patients with R-ISS III, it is possible to improve long-term survival after ASCT by increasing the MRD negative rate before ASCT by adding induction chemotherapy and other methods ( 15 , 23 ). We are convinced that the time has come to use it to adapt the treatment strategy to a dynamic risk ( 10 , 20 ). The current guidelines recommend that patients with NDMM eligible for transplantation require 4–6 courses of induction chemotherapy ( 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…The pretransplantation MRD level was an independent prognostic factor for event-free survival (EFS) and OS ( 9 ). MRD status by MFC at day 100 or 365 after ASCT was the most important independent prognostic factor for PFS and OS ( 3 , 10 ). These findings demonstrate the clinical importance of MRD evaluation, and the MRD-negative status has become the goal of current treatment, and it has also become the endpoint of many clinical trials ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of the Stage at Which an MRD-Negative Status Is Achieved for Patients With Multiple Myeloma Who Received ASCT

Sun

et al. 2022

Front. Oncol.

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ObjectiveTo explore the prognostic significance of the stage at which a minimal residual disease (MRD)-negative status is achieved for patients with newly diagnosed multiple myeloma (NDMM) who received autologous hematopoietic stem cell transplantation (ASCT).Cases and MethodsA retrospective analysis of 186 NDMM patients who received “induction therapy-ASCT-maintenance therapy” in our center and achieved an MRD-negative status was performed. Patients were divided into three groups, A (induction therapy), B (3 months after ASCT), and C (maintenance therapy), according to the stage at which an MRD-negative status was achieved.ResultsThe median time to progression (TTP) of 186 patients was not reached; the median overall survival (OS) was 113.8 months. The median TTP of the patients in three groups was not reached (P=0.013), and the median OS of the patients in three groups was not reached, not reached, and 71.2 months, respectively (P=0.026). Among patients with standard-risk cytogenetics, the median TTP of those in all three groups was not reached (P=0.121), and the median OS of the patients in three groups was not reached, not reached, and 99.6 months, respectively (P=0.091). Among patients with high-risk cytogenetics, the median TTP of those in three groups was not reached, 53.9 months, and 35.8 months (P=0.060), and the median OS was not reached, 71.2 months, and 60.2 months, respectively (P=0.625). Among patients with R-ISS stage I-II, the median TTP of those in three groups was not reached (P=0.174), and the median OS of the patients in three groups was not reached, not reached, and 99.6 months, respectively (P=0.186). Among the 29 patients with R-ISS stage III, the median TTP of those in the 3 groups were unreached, unreached, and 35.1 months (P<0.001), and the median OS was unreached, unreached, and 48.5 months, respectively (P=0.020). In all enrolled patients, the stage of reaching MRD-negative was an independent prognostic factor for TTP, rather than a prognostic factor for OS. The stage of reaching MRD-negative in patients with R-ISS III was an independent prognostic factor for OS.ConclusionFor the same patients who are MRD-negative, the prognoses of those who achieve an MRD-negative status at different groups are different. The stage at which an MRD-negative status is achieved can predict the prognosis of patients with R-ISS stage III.

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“…According to a meta-analysis, LEN maintenance therapy prolonged PFS and OS [ 126 , 127 ]. In addition, LEN maintenance therapy achieved and maintained MRD negativity compared with no maintenance therapy [ 128 ]. In the TOURMALINE-MM3 trial, post-transplantation ixazomib maintenance therapy prolonged PFS and prevented conversion from MRD negative to positive compared with placebo in MRD-negative patients before maintenance therapy [ 129 ].…”

Section: Current Treatment To Achieve Persistent Mrd-negativitymentioning

confidence: 99%

Treatment Strategy for Multiple Myeloma to Improve Immunological Environment and Maintain MRD Negativity

Suzuki

Nishiwaki

Yano

2021

Cancers

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Improving the immunological environment and eradicating minimal residual disease (MRD) are the two main treatment goals for long-term survival in patients with multiple myeloma (MM). Immunomodulatory drugs (IMiDs), monoclonal antibody drugs (MoAbs), and autologous grafts for autologous stem cell transplantation (ASCT) can improve the immunological microenvironment. ASCT, MoAbs, and proteasome inhibitors (PIs) may be important for the achievement of MRD negativity. An improved immunological environment may be useful for maintaining MRD negativity, although the specific treatment for persistent MRD negativity is unknown. However, whether the ongoing treatment should be continued or changed if the MRD status remains positive is controversial. In this case, genetic, immunophenotypic, and clinical analysis of residual myeloma cells may be necessary to select the effective treatment for the residual myeloma cells. The purpose of this review is to discuss the MM treatment strategy to “cure MM” based on currently available therapies, including IMiDs, PIs, MoAbs, and ASCT, and expected immunotherapies, such as chimeric antigen receptor T cell (CAR-T) therapy, via improvement of the immunological environment and maintenance of MRD negativity.

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Minimal residual disease negativity and lenalidomide maintenance therapy are associated with superior survival outcomes in multiple myeloma

Cited by 8 publications

References 45 publications

Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma

Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma

Prognostic Significance of the Stage at Which an MRD-Negative Status Is Achieved for Patients With Multiple Myeloma Who Received ASCT

Treatment Strategy for Multiple Myeloma to Improve Immunological Environment and Maintain MRD Negativity

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