Integrated analysis of next generation sequencing minimal residual disease (MRD) and PET scan in transplant eligible myeloma patients

Fonseca-Portilla, Rodrigo; Arribas, Mariano; Wiedmeier-Nutor, Julia E.; Kusne, Yael; Vélez, Miguel González; Kosiorek, Heidi E.; Butterfield, Richard Duke J; Kirsch, Ilan R.; Mıkhael, Joseph; Stewart, A. Keith; Reeder, Craig B.; Larsen, Jeremy T.; Bergsagel, P. Leif; Fonseca, Rafaël

doi:10.1038/s41408-023-00794-x

Cited by 12 publications

(6 citation statements)

References 42 publications

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“…Sustained MRDneg status at months 6 and 12 have been persistently found to be prognostic for prolonged PFS in other myeloma therapies [ 11 ]. Our serial BM MRD data in CAR-T patients corroborates these findings.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of early bone marrow MRD status in CAR-T therapy for myeloma

et al. 2023

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Bone marrow (BM) assessment of minimal residual disease (MRD) is prognostic for survival in multiple myeloma (MM). BM is still hypocellular at month 1 post CAR-T, thus the value of MRD negative (MRDneg) status at this timepoint is unclear. We examined the impact of month 1 BM MRD status in MM patients who received CART at Mayo Clinic between 8/2016 and 6/2021. Among 60 patients, 78% were BM-MRDneg at month 1; and 85% (40/47) of these patients also had decreased to less than normal level of both involved and uninvolved free light chain (FLC < NL). Patients who achieved CR/sCR had higher rates of month 1 BM-MRDneg and FLC < NL. The rate of sustained BM-MRDneg was 40% (19/47). Rate of conversion from MRDpos to MRDneg was 5%(1/20). At month 1, 38%(18/47) of the BM-MRDneg were hypocellular. Recovery to normal cellularity was observed in 50%(7/14) with a median time to normalization at 12 months (range: 3–Not reached). Compared to Month 1 BM-MRDpos patients, patients who were BM-MRDneg had longer PFS irrespective of BM cellularity [PFS: 2.9 months (95% CI, 1.2-NR) vs. 17.5 months (95% CI, 10.4-NR), p < 0.0001]. Month 1 BM-MRDneg and FLC below normal were associated with prolonged survival. Our data support the continued evaluation of BM early post-CART infusion as a prognostic tool.

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Section: Discussionmentioning

confidence: 99%

Prognostic value of early bone marrow MRD status in CAR-T therapy for myeloma

et al. 2023

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“…When undergoing BM assessment 100 days post-autologous hematopoietic stem cell transplant (ASCT), patients with NGS-MRD-negative status at 10 −6 had longer TTNT than those with MRD negativity at 10 −5 and positivity, regardless of therapy, cytogenetic risk, and/or R-ISS stage. Almost all NGS-MRD-negative patients were 18 F-FDG PET-negative [ 58 ]. Although MRD assessment shows significantly higher sensitivity than assessment by the current PET imaging, PET imaging provides a considerable benefit over other techniques for assessing lesion extent and disease activity in patients with MM.…”

Section: Positron Emission Tomography (Pet)mentioning

confidence: 99%

Current and Future PET Imaging for Multiple Myeloma

Ishibashi,

Takahashi,

Yamaya

et al. 2023

Life

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Positron emission tomography (PET) is an imaging modality used for the noninvasive assessment of tumor staging and response to therapy. PET with 18F labeled fluorodeoxyglucose (18F-FDG PET) is widely used to assess the active and inactive lesions in patients with multiple myeloma (MM). Despite the availability of 18F-FDG PET for the management of MM, PET imaging is less sensitive than next-generation flow cytometry and sequencing. Therefore, the novel PET radiotracers 64Cu-LLP2A, 68Ga-pentixafor, and 89Zr-daratumumab have been developed to target the cell surface antigens of MM cells. Furthermore, recent studies attempted to visualize the tumor-infiltrating lymphocytes using PET imaging in patients with cancer to investigate their prognostic effect; however, these studies have not yet been performed in MM patients. This review summarizes the recent studies on PET with 18F-FDG and novel radiotracers for the detection of MM and the resulting preclinical research using MM mouse models and clinical studies. Novel PET technologies may be useful for developing therapeutic strategies for MM in the future.

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“…PET/CT may safeguard against false-negative MRD testing, though with adequate marrow sampling (input) and deeper MRD assessment, the value of PET/CT may be lower. In fact, in recent reports, there has been little discordance between PET and MRD at 10 –5 —10 –6 sensitivity suggesting there may be a more limited role to combined assessment [ 30 ]. While PET-CT generally remains the standard for imaging post-response, whole-body diffusion-weighted MRI (DW-MRI) has strong utility in capturing focal lesions that might have increased relevance in the MRD setting [ 26 ].…”

Section: Readily Available and Actionable Mrd Assaysmentioning

confidence: 99%

Minimal Residual Disease-Adapted Therapy in Multiple Myeloma: Current Evidence and Opinions

Meseha,

Hoffman,

Kazandjian

et al. 2024

Curr Oncol Rep

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Purpose of Review Multiple myeloma (MM) is a biologically heterogeneous malignancy with relatively uniform treatment paradigms. This review aims to assess the growing role of Minimal Residual Disease (MRD) assessment in facilitating response-adapted therapeutic decision making to individualize therapy in MM. Recent Findings MRD has been repeatedly demonstrated to provide strong prognostic information, superseding traditional IMWG response criteria. The use of MRD to modulate therapy remains controversial. Here, we review the existing landscape of MRD-adapted trial designs in both induction/consolidation and maintenance settings, including recent data from influential studies and retrospective analyses. We navigate existing data, leverage the increased resolution of longitudinal MRD assessments, and comment on trials in progress to explain our current utilization of MRD in the clinic. Summary MRD transcends traditional response assessments by providing a window into disease-treatment interaction over time. As a strong patient-level surrogate, MRD has limited current use in individualizing treatment, but is poised to comprehensively shape treatment strategies at many key points in a patient’s MM course.

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Integrated analysis of next generation sequencing minimal residual disease (MRD) and PET scan in transplant eligible myeloma patients

Cited by 12 publications

References 42 publications

Prognostic value of early bone marrow MRD status in CAR-T therapy for myeloma

Prognostic value of early bone marrow MRD status in CAR-T therapy for myeloma

Current and Future PET Imaging for Multiple Myeloma

Minimal Residual Disease-Adapted Therapy in Multiple Myeloma: Current Evidence and Opinions

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