Treatment Regimens for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: A Systematic Literature Review and Network Meta-analysis

Facon, Thierry; San-Miguel, Jesús F.; Dimopoulos, Meletios A.; Mateos, María‐Victoria; Cavo, Michèle; Beekhuizen, S. van; Yuan, Zhenhong; Mendes, João; Lam, Annette; He, Jianming; Ammann, Eric M.; Kumar, Shaji

doi:10.1007/s12325-022-02083-8

Cited by 18 publications

(9 citation statements)

References 38 publications

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“…Similar questions exist also for the non-transplant-eligible patients, where the positive impact of continuous treatment on OS is not well demonstrated ( 71 , 73 , 74 ). Clinical trials where MRD-negative patients are randomized to therapy suspension or continuation until disease progression or intolerance will prove informative.…”

Section: Minimal Residual Disease In Therapeutic Decision: Ready For ...mentioning

confidence: 83%

Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy

Ferla¹,

Antonini

Perini

et al. 2022

Front. Oncol.

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Assessment of minimal residual disease (MRD) is becoming a standard diagnostic tool for curable hematological malignancies such as chronic and acute myeloid leukemia. Multiple myeloma (MM) remains an incurable disease, as a major portion of patients even in complete response eventually relapse, suggesting that residual disease remains. Over the past decade, the treatment landscape of MM has radically changed with the introduction of new effective drugs and the availability of immunotherapy, including targeted antibodies and adoptive cell therapy. Therefore, conventional serological and morphological techniques have become suboptimal for the evaluation of depth of response. Recently, the International Myeloma Working Group (IMWG) introduced the definition of MRD negativity as the absence of clonal Plasma cells (PC) with a minimum sensitivity of <10−5 either by next-generation sequencing (NGS) using the LymphoSIGHT platform (Sequenta/Adaptative) or by next-generation flow cytometry (NGF) using EuroFlow approaches as the reference methods. While the definition of the LymphoSIGHT platform (Sequenta/Adaptive) as the standard method derives from its large use and validation in clinical studies on the prognostic value of NGS-based MRD, other commercially available options exist. Recently, the LymphoTrack assay has been evaluated in MM, demonstrating a sensitivity level of 10−5, hence qualifying as an alternative effective tool for MRD monitoring in MM. Here, we will review state-of-the-art methods for MRD assessment by NGS. We will summarize how MRD testing supports clinical trials as a useful tool in dynamic risk-adapted therapy. Finally, we will also discuss future promise and challenges of NGS-based MRD determination for clinical decision-making. In addition, we will present our real-life single-center experience with the commercially available NGS strategy LymphoTrack-MiSeq. Even with the limitation of a limited number of patients, our results confirm the LymphoTrack-MiSeq platform as a cost-effective, readily available, and standardized workflow with a sensitivity of 10−5. Our real-life data also confirm that achieving MRD negativity is an important prognostic factor in MM.

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Section: Minimal Residual Disease In Therapeutic Decision: Ready For ...mentioning

confidence: 83%

Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy

Ferla¹,

Antonini

Perini

et al. 2022

Front. Oncol.

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“…TTNT curves for VRd were derived by applying PFS hazard ratios from a published network meta-analysis. 18 A TTNT HR for VRd was not available; however, in similar studies, the HRs for TTNT and PFS are usually very similar (eg, in MAIA, PFS HR was 0.53 [95% CI, 0.43-0.66] and TTNT HR was 0.47 [95% CI, 0.37-0.59] 12 ). Therefore, PFS HR was used as a proxy in the current model.…”

Section: Methodsmentioning

confidence: 99%

“…To inform 1L, 1-month transition probabilities were derived from time to next treatment (TTNT; defined as time to next treatment line or death), PFS, and OS data from the MAIA trial 12 , 17 and SWOG S0777 (based on a published network meta-analysis 18 ). Real-world data from the Flatiron Health database were used to inform 2L.…”

Section: Methodsmentioning

confidence: 99%

Impact of Treatment Sequencing on Overall Survival in Patients with Transplant-Ineligible Newly Diagnosed Myeloma

et al. 2023

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Background Because patients with newly diagnosed multiple myeloma (NDMM) do not always receive any treatment beyond first-line (1L) therapy, it is imperative that patients receive the best treatment in the 1L setting. However, the optimal initial treatment remains to be identified. We performed a clinical simulation to assess potential outcomes with different treatment sequences. Patients and Methods We used a partitioned survival model to compare overall survival (OS) with (1) daratumumab, lenalidomide, and dexamethasone (D-Rd) in 1L followed by a pomalidomide- or carfilzomib-based regimen in second line (2L) versus (2) bortezomib, lenalidomide, and dexamethasone (VRd) in 1L followed by a daratumumab-based regimen in 2L versus (3) lenalidomide and dexamethasone (Rd) in 1L followed by a daratumumab-based regimen in 2L. Probabilities of transition between health states (1L, 2L+, and death) were based on published clinical data and real-world data from the Flatiron Health database. The proportion of patients discontinuing treatment after 1L (attrition rates) in the base case was estimated with a binomial logistic model using data from the MAIA trial. Results Using D-Rd in 1L conferred a longer median OS compared with delaying daratumumab-based regimens until 2L after VRd or Rd, respectively (8.9 [95% CrI 7.58-10.42] vs. 6.92 [5.92-8.33] or 5.75 [4.50-7.25] years). Results of scenario analyses were consistent with the base case. Conclusion Our simulation, which incorporates clinically representative treatments and attrition rates, supports the use of D-Rd as initial therapy, rather than delaying the use of daratumumab until later lines of therapy, in patients with transplant-ineligible NDMM.

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“…A network meta-analysis by Facon et al (2022) showed that daratumumab-based regimens, including D-Rd, D-VMP, and VRd, had the highest probabilities of being more effective than Rd continuous in terms of PFS (HR: D-Rd, 0.53; D-VMP, 0.57; VRd, 0.77) and OS (HR: D-Rd, 0.68; VRd, 0.77; D-VMP, 0.78) for NDMM patients. Among them, D-Rd ranked first as the most effective treatment in terms of PFS and OS.…”

Section: Expert Opinionmentioning

confidence: 99%

Quadruplet regimen for newly diagnosed multiple myeloma is effective in the standard-risk subgroup but not in the high-risk subgroup

Ding,

Gong

2024

Front. Pharmacol.

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Treatment Regimens for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: A Systematic Literature Review and Network Meta-analysis

Cited by 18 publications

References 38 publications

Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy

Minimal residual disease detection by next-generation sequencing in multiple myeloma: Promise and challenges for response-adapted therapy

Impact of Treatment Sequencing on Overall Survival in Patients with Transplant-Ineligible Newly Diagnosed Myeloma

Quadruplet regimen for newly diagnosed multiple myeloma is effective in the standard-risk subgroup but not in the high-risk subgroup

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