Risk-Adapted Therapy Directed According to Response (RADAR, UK-MRA Myeloma XV) - Comparing MRD-Guided Treatment Escalation and De-Escalation Strategies in Patients with Newly Diagnosed Myeloma Suitable for Stem Cell Transplantation

Yong, Kwee; Royle, Kara-Louise; Ramasamy, Karthik; Parrish, Christopher; Hockaday, Anna; Asher, Samir; Drayson, Mark T.; Tute, Ruth M. de; Jenner, Matthew; Kaiser, Martin; Pratt, Guy; Sive, Jonathan; Bygrave, Ceri; Cook, Gordon; Popat, Rakesh; Smith, Dean; Olivier, C; Barnard, Lorna; Levinte, Doina; Dawkins, Bryony; Chapman, Michael A.; Chantry, Andrew; Jackson, Graham; Quezada, Sergio A.; Owen, Roger G.; Cairns, David A.

doi:10.1182/blood-2022-168842

Cited by 5 publications

(6 citation statements)

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“…Similarly, MRD testing by NGF or NGS, proved to be a more powerful factor in affecting PFS and OS than cytogenetics or ISS stage in several studies [ 121 , 122 ], but it suffers from several issues limiting its incorporation in daily practice. Clinical studies did not definitively clarify neither what the ideal threshold of sensitivity is, the optimal timing for MRD assessment, nor if achievement of MRD negativity has the same value in SR, HR or ultra-high-risk patients, given that the MASTER trial [ 130 ] showed different outcomes in these groups of patients despite MRD negativity. Moreover, the discordance between the achievement of CR according to IMWG criteria [ 120 ] and MRD negativity [ 241 ] should be better explained.…”

Section: Discussion and Expert Opinionmentioning

confidence: 99%

“…However, based on the significant MRD negativity rates obtained with continuous therapies or through the different phases of treatment, sequential MRD evaluation could better assess the efficacy of each treatment phases, allowing therapy escalation or de-escalation with the aim to minimize toxicity and costs. Ongoing phase III trials [ 88 , 105 , 117 , 129 , 130 ] will enable us to understand if MRD-driven approach will be the right tool to personalize therapy. Early results on the comparison between bone marrow data and peripheral blood MRD assessment by mass spectrometry (MS) seem to be promising—and this and other similar techniques may represent a turning point in the clinical practice.…”

Section: Discussion and Expert Opinionmentioning

confidence: 99%

“…Ongoing randomized phase II MASTER-2 trial will evaluate, after 6 cycles of Dara-VRD as induction, ASCT vs. 3 additional cycles of Dara-VRD, in MRD negative patients after induction whereas positive patients will undergo ASCT followed by teclistamab plus daratumumab vs. daratumumab plus lenalidomide. In the phase II/III RADAR (UK-MRA Myeloma XV) study [ 130 ], which will enroll 1400 patients, treatment will be deescalated after ASCT in patients with MRD negativity whereas those with persistent MRD positivity will be randomized to different regimens ranging from lenalidomide monotherapy to isatuximab, lenalidomide, bortezomib, dexamethasone (Isa-RBorD). This trial could answer two key questions: how to maintain MRD negativity when it has been achieved and how to obtain MRD negativity if not previously achieved.…”

Section: Minimal Residual Disease (Mrd) In the Era Of New Drugs And M...mentioning

confidence: 99%

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Current Main Topics in Multiple Myeloma

Morè¹,

Corvatta²,

Manieri³

et al. 2023

Cancers

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Multiple Myeloma (MM) remains a difficult to treat disease mainly due to its biological heterogeneity, of which we are more and more knowledgeable thanks to the development of increasingly sensitive molecular methods that allow us to build better prognostication models. The biological diversity translates into a wide range of clinical outcomes from long-lasting remission in some patients to very early relapse in others. In NDMM transplant eligible (TE) patients, the incorporation of mAb as daratumumab in the induction regimens, followed by autologous stem cell transplantation (ASCT) and consolidation/maintenance therapy, has led to a significant improvement of PFS and OS.; however, this outcome remains poor in ultra-high risk MM or in those who did not achieve a minimal residual disease (MRD) negativity. Several trials are exploring cytogenetic risk-adapted and MRD-driven therapies in these patients. Similarly, quadruplets-containing daratumumab, particularly when administered as continuous therapies, have improved outcome of patients not eligible for autologous transplant (NTE). Patients who become refractory to conventional therapies have noticeably poor outcomes, making their treatment a difficult challenge in need of novel strategies. In this review, we will focus on the main points regarding risk stratification, treatment and monitoring of MM, highlighting the most recent evidence that could modify the management of this still incurable disease.

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Section: Discussion and Expert Opinionmentioning

confidence: 99%

Section: Discussion and Expert Opinionmentioning

confidence: 99%

Section: Minimal Residual Disease (Mrd) In the Era Of New Drugs And M...mentioning

confidence: 99%

See 1 more Smart Citation

Current Main Topics in Multiple Myeloma

Morè¹,

Corvatta²,

Manieri³

et al. 2023

Cancers

View full text Add to dashboard Cite

show abstract

“…This study has demonstrated the feasibility of using sustained MRD negativity to guide maintenance with comparable PFS and OS outcomes in high‐risk patients. Lastly, the UK RADAR (Risk‐Adapted therapy Directed According to Response) trial is a randomised multiarm phase 2/3 study that aims to recruit 1400 patients who will receive lenalidomide, cyclophosphamide, bortezomib, dexamethasone (RCyBoRD) based induction followed by HDM and AHCT with subsequent consolidation and maintenance based on cytogenetic risk and MRD status post‐AHCT 81 . In standard risk patients, the study aims to assess the effect of stopping isatuximab maintenance in MRD‐negative patients and the benefit of intensification of consolidation and maintenance with R‐Isa in those with persistent measurable disease.…”

Section: Role Of Maintenance: Conventional Agentsmentioning

confidence: 99%

The role of maintenance therapy following autologous stem cell transplantation in newly diagnosed multiple myeloma: Considerations on behalf of the Chronic Malignancies Working Party of the EBMT

Hwang,

Hayden,

Pawlyn

et al. 2024

Br J Haematol

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SummaryRecent treatment advancements in multiple myeloma have led to significant improvements in patient outcomes. Maintenance therapy following autologous haematopoietic stem cell transplantation (AHCT) is now standard of care and has been demonstrated to prolong and deepen treatment responses. Currently, lenalidomide remains the single agent that has been approved for maintenance post‐AHCT in Europe and the USA which, if tolerated, is continued until disease progression. The treatment landscape is rapidly expanding however, and the optimal personalised maintenance approach for a patient is becoming more complex. Treatment outcomes for patients with high‐risk disease remain poor and choice of maintenance in this population also remains unclear. This review article evaluates up‐to‐date literature regarding established maintenance approaches. It further analyses ongoing studies exploring maintenance regimens using combination and novel agents, approaches to maintenance in patients with cytogenetic high‐risk disease and minimal residual disease response‐adapted strategies that reflect the current evolving treatment paradigm.

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“…Moreover, considering previous studies have proven that MRD are of great value in adapting chemotherapy and HSCT therapy, MRD assessment also has the potential to guide the adjustment of CAR-T cell therapy strategy. [44] It is worth exploring whether patients with positive MRD should be recommended to undergo more intensive preparative regimens and higher doses of cell infusions compared to MRD-negative patients. However, there is currently limited research data available in this regard.…”

Section: Mrd-directed Car-t-cell Therapy: Enhancing Precision and Eff...mentioning

confidence: 99%

Current assessment and management of measurable residual disease in patients with acute lymphoblastic leukemia in the setting of CAR-T-cell therapy

Lin,

Zhao,

Chang

et al. 2023

Chin Med J

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Chimeric antigen receptor (CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia (ALL). Measurable/minimal residual disease (MRD) monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy. Common MRD detection methods include flow cytometry (FCM), polymerase chain reaction (PCR), and next-generation sequencing (NGS), and each method has advantages and limitations. It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse. Thus, how to perform prognostic evaluations, stratify risk based on MRD status, and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice. This review assesses the common and novel MRD assessment methods. In addition, we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT), as well as other therapeutic strategies to improve treatment effect. Furthermore, this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.

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Risk-Adapted Therapy Directed According to Response (RADAR, UK-MRA Myeloma XV) - Comparing MRD-Guided Treatment Escalation and De-Escalation Strategies in Patients with Newly Diagnosed Myeloma Suitable for Stem Cell Transplantation

Cited by 5 publications

References 0 publications

Current Main Topics in Multiple Myeloma

Current Main Topics in Multiple Myeloma

The role of maintenance therapy following autologous stem cell transplantation in newly diagnosed multiple myeloma: Considerations on behalf of the Chronic Malignancies Working Party of the EBMT

Current assessment and management of measurable residual disease in patients with acute lymphoblastic leukemia in the setting of CAR-T-cell therapy

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