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Analysis of baseline circulating tumor cells integrated with PET/CT findings in transplant-ineligible multiple myeloma.

ABSTRACT:

Abstract

We aimed to improve prognostic predictors in patients with transplant-ineligible multiple myeloma (TIE-MM) by combining baseline circulating clonal tumor cells (CTCs) and positron emission tomography/computed tomography (PET/CT) findings. The factors associated with prognosis were retrospectively investigated in 126 patients with TIE-MM who underwent CTC quantification by multiparameter flow cytometry and PET/CT at the initial presentation. The total lesion glycolysis (TLG) level was calculated using the Metavol software. The median percentage of CTC was 0.06% (range, 0%-4.82%), and 54 patients (42.9%) demonstrated high CTC levels. High CTC levels were associated with significantly poorer progression-free survival (PFS, 2-year 43.4% vs 68.1%; P < .001) and overall survival (OS, 5-year 39.0% vs 68.3%; P < .001). Similarly, high TLG levels significantly worsened the PFS (2-year, 41.2% vs 67.6%; P = .038) and OS (5-year, 37.7% vs 63.1%; P = .019). The multivariate analyses showed that Revised International Staging System (R-ISS) III, high CTC and TLG levels, and complete response were significant prognostic factors for PFS and OS. A novel predictive model was constructed using CTCs, TLG, and R-ISS III. The patients were stratified into 3 groups according to the number of risk factors, revealing an extremely high-risk group with a 2-year PFS of 0% and a 5-year OS of 20%. Patients without any high-risk features had better prognosis, with a 2-year PFS of 78.6% and a 5-year OS of 79.5%. The combination of CTCs and volumetric assessment of PET/CT at diagnosis augments the existing stratification systems and may pave the way for a risk-adapted treatment approach.

SUBMITTER: Ikeda D

PROVIDER: S-EPMC10784675 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Analysis of baseline circulating tumor cells integrated with PET/CT findings in transplant-ineligible multiple myeloma.

Ikeda Daisuke D Terao Toshiki T Oura Mitsuaki M Uehara Atsushi A Tabata Rikako R Narita Kentaro K Takeuchi Masami M Machida Youichi Y Matsue Kosei K

Blood advances 20240101 1

<h4>Abstract</h4>We aimed to improve prognostic predictors in patients with transplant-ineligible multiple myeloma (TIE-MM) by combining baseline circulating clonal tumor cells (CTCs) and positron emission tomography/computed tomography (PET/CT) findings. The factors associated with prognosis were retrospectively investigated in 126 patients with TIE-MM who underwent CTC quantification by multiparameter flow cytometry and PET/CT at the initial presentation. The total lesion glycolysis (TLG) leve ...[more]

PMID: 38150271

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Project description:ImportanceAlthough the number of treatments for elderly patients with non-transplant-eligible (NTE) multiple myeloma (MM) has increased substantially, evidence is lacking on the clinical effectiveness and cost-effectiveness of novel treatment sequences.ObjectiveTo determine the optimal sequence of treatment for patients with NTE MM from the perspective of the patient, physician, and society.Design, setting, and participantsUsing data from a Dutch observational registry, this economic evaluation combined evidence from network meta-analyses in a patient-level simulation model and modeled time-to-event and types of events from a hospital perspective with a lifetime horizon. Data analysis was performed from June 2019 to September 2020.InterventionsThirty treatment sequences, including up to 3 lines of therapy, were compared with bortezomib-melphalan-prednisone (VMP)-lenalidomide-dexamethasone (LenDex)-pomalidomide-dexamethasone (PomDex).Main outcomes and measuresThe primary outcomes of the model were overall survival (OS), quality-adjusted life-years (QALYs), costs, and cost-effectiveness.ResultsSequences starting with daratumumab-VMP (second line: carfilzomib-lenalidomide-dexamethasone or elotuzumab-lenalidomide-dexamethasone) or bortezomib-melphalan-prednisone-thalidomide-maintenance bortezomib-thalidomide (VMPT-VT) (second line: daratumumab-lenalidomide-dexamethasone) had the largest expected OS (7.5 years), which is 3.5 additional life-years compared with VMP-LenDex-PomDex. Total costs per patient for these sequences ranged between $786 024 and $1 085 794. The sequence VMPT-VT-carfilzomib-lenalidomide-dexamethasone-panobinostat-bortezomib-dexamethasone had the most favorable cost-effectiveness ratio ($98 585 per life-year gained and $132 707 per QALY gained vs VMP-LenDex-PomDex).Conclusions and relevanceThese findings suggest that sequences including novel treatments were highly effective, but the cost-effectiveness ratios were above currently accepted willingness-to-pay thresholds. Treating MM with novel agents necessitates either a large increase in budget or a substantial reduction of drug costs by price negotiations, and these findings can support these reimbursement decisions and price negotiations.

Project description:IntroductionPatients with transplant-ineligible (TIE) multiple myeloma (MM) have high rates of symptom burden. The aim of this study was to develop and validate a prognostic model to predict symptoms in patients with TIE MM.MethodsIn this population-based, retrospective cohort study, using multiple administrative health care databases linked using a unique encrypted patient identifier in Ontario, Canada, symptoms were identified using the patient self-reported Edmonton Symptom Assessment System (ESAS) at each clinic visit. The primary outcome was the presence of moderate-to-severe (ESAS score 4-10) symptoms (specifically symptoms of pain, tiredness, depression, and impaired well-being) within one year from the index date. Using the entire cohort, a multivariable logistic regression model with baseline covariates was developed to predict the risk of experiencing each of the above symptoms, categorized as moderate to severe within 1 year post-index date. Internal validation of the model was assessed via bootstrap validation methods.ResultsA total of 1535 TIE adults with MM met the inclusion criteria. The median age was 75, with 25.2% of patients aged 80 years or older. In the multivariate analysis, baseline symptoms continued to be most associated with future symptom burden. Baseline severe pain (OR 9.84, 95% CI 6.29-15.7) was most associated with patients experiencing moderate-severe pain one year post-index date. Similarly, baseline severe tiredness (OR 17.34, 95% CI 9.00-33.42), baseline severe depression (OR 28.07, 95% CI 15.96-49.38), and baseline severely impaired well-being (OR 4.12, 95% CI 2.30-7.37) were the biggest predictors of patients experiencing moderate-severe tiredness, depression, and impaired well-being, respectively, at one year after the index date.ConclusionsPatients with MM experience persisting symptoms of pain, tiredness, depression, and impaired well-being, with baseline symptoms being the biggest predictor of future symptom burden.

Dataset Information

Analysis of baseline circulating tumor cells integrated with PET/CT findings in transplant-ineligible multiple myeloma.

Abstract

Publications

Analysis of baseline circulating tumor cells integrated with PET/CT findings in transplant-ineligible multiple myeloma.

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