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Myeloma News

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Myeloma News

Novel Model Effectively Predicts Early Relapse After CAR-T Therapy in Myeloma

Source: Myeloma – Hematology Advisor

A novel prognostic model may aid in the timing of chimeric antigen receptor (CAR) T-cell therapy among patients with relapsed or refractory multiple myeloma (MM), according to research published in the Journal of Clinical Oncology.

Many patients with relapsed or refractory MM have benefited from the introduction of CAR-T therapies, which have induced complete remissions successfully in this difficult-to-treat population. Early relapse to CAR-T cell therapy, however, remains a significant concern, and is linked with a heightened risk of mortality.

This risk necessitates a model that effectively predicts early relapse, which may help to optimize timing of CAR-T therapy. For this retrospective study, researchers evaluated characteristics and outcomes among patients with relapsed or refractory MM who received a B-cell maturation antigen-targeting CAR-T therapy to create a novel model for predicting early relapse. 

Data from 269 patients were included and divided into 2 cohorts: a European cohort (136 patients) and a United States cohort (133 patients). Patients received academic CAR-T cells (60 patients), idecabtagene ciloleucel (171 patients), or ciltacabtagene autoleucel (38 patients).

Analysis of outcomes in the 2 cohorts showed an overall response rate of 87% in both. The complete response rate in the European cohort was 48% compared with 49% in the United States. Moreover, the median time to relapse was 5 months.

We provide the first Euro-American cartography of the efficacy and safety profile of current CAR-T, showing comparable results.

Further analysis showed that early relapse (defined as less than 5 months from infusion) was linked with a 12-month overall rate of 30% in Europe and 14% in the United States.

The researchers used 4 independent predictive factors to form their model, the Myeloma CAR-T Relapse (MyCARe) model: the presence of extramedullary disease/plasma cell leukemia, disease refractory to lenalidomide, high-risk cytogenetics, and increased ferritin at lymphodepletion. These formed the 4-point, 3-tiered MyCARe mode.

Evaluation of MyCARe showed that the model effectively predicted 5-month incidence of relapse or progression: 7% risk among patients with low-risk disease, 27% for intermediate risk, and 53% for high risk (P <.001). Validation of the model on the US cohort maintained MyCARe’s prognostic utility.

“In summary, we provide the first Euro-American cartography of the efficacy and safety profile of current CAR-T, showing comparable results,” the authors wrote in their report. “We also built the MyCARe model, which can predict early relapse, response, and survival and may facilitate patient selection in this very challenging setting.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.

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Study Identifies Factors Linked to Unsustained MRD in Multiple Myeloma

Source: Myeloma – Hematology Advisor

In transplant-eligible patients with newly diagnosed multiple myeloma (MM), a recent study identified factors related to whether measurable residual disease (MRD) negativity was sustained over time. Study results were reported in the journal Blood.

The study was a retrospective analysis of data obtained from the FORTE trial (ClinicalTrials.gov Identifier: NCT02203643), which enrolled transplant-eligible patients with newly diagnosed MM. 

In this analysis, the researchers evaluated data from the study to identify possible factors associated with losing MRD negativity over time. This analysis had a primary endpoint of the cumulative incidence of MRD resurgence or progressive disease after MRD negativity was initially established. 

MRD negativity was characterized through the use of multiparametric flow cytometry, with a sensitivity of 10-5. MRD was assessed at the time of suspected complete response, at premaintenance in patients with a very good partial response or better, and at 6-month intervals during maintenance. 

There were 474 patients enrolled, of whom 310 (65%) reached MRD negativity. Among those with MRD negativity, 306 patients were included in further analyses. Patients had a median time to first MRD negativity of 8.9 months. 

With a median follow-up of 50.4 months after MRD negativity was demonstrated, there were 185 patients (60%) who continued to have MRD negativity and progression-free status. However, there were 118 patients (39%) who had lost MRD-negative status, and 3 patients (1%) died but had not experienced disease progression. 

Among the 118 patients in whom MRD negativity was not sustained, MRD positivity was observed in bone marrow prior to the onset of progressive disease in 70 patients (59%). Criteria for progressive disease were met before detection of bone marrow MRD positivity in 48 patients (41%).

The results of our analysis…should be validated in larger prospective cohorts of patients, including daratumumab-based combinations and new immune therapies.

A greater risk of unsustained MRD negativity appeared significantly associated with multiple factors. These included the presence of 1q amplification (hazard ratio [HR], 2.07; 95% CI, 1.12-3.82; P =.02), having 2 or more high-risk cytogenetic abnormalities rather than 0 (HR, 2.22; 95% CI, 1.33-3.71; P =.0024), a high baseline level of circulating tumor cells (HR, 1.86; 95% CI, 1.17-2.96; P =.008), and a time to first MRD negativity occurring after the start of consolidation rather than preconsolidation (HR, 1.56; 95% CI, 1.04-2.32; P =.029).

A factor associated with a lower risk of unsustained MRD negativity was the use of carfilzomib combined with lenalidomide during the first 2 years of maintenance therapy, compared with receiving lenalidomide alone (HR, 0.58; 95% CI, 0.35-0.96; P =.033).

“The results of our analysis, limited by the number of patients and the retrospective nature, should be validated in larger prospective cohorts of patients, including daratumumab-based combinations and new immune therapies,” the researchers wrote in their report. 

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

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Functional Disability Predicts Mortality in Older Adults With Newly Diagnosed Multiple Myeloma

Source: Myeloma – Hematology Advisor

Among older adults with multiple myeloma (MM) receiving home health services, functional disability is a predictor of early mortality, according to research published in JCO Clinical Cancer Informatics.

“The care of patients with MM is often challenging because of the higher prevalence of vulnerabilities observed with advancing age, a risk factor associated with MM incidence,” the authors wrote in their report.

The researchers retrospectively evaluated the relationships between disability, treatment receipt, and survival outcomes in older adults with newly diagnosed MM using the US nationwide Surveillance, Epidemiology, and End Results (SEER)-Medicare data set. 

The study included adults aged ≥66 years diagnosed with MM from 2010 to 2017 who used home health services the year before diagnosis. At home health assessment, patients’ degree of functional disability was assessed using a composite score derived from items related to ability to complete activities of daily living. The primary outcome was overall mortality, and secondary outcomes included receipt of any MM therapy in the year after diagnosis, treatment type, and health care utilization.

A total of 37,280 adults aged ≥66 years were diagnosed with MM from 2010 to 2017. Of those, 18.2% used home health services in the year before diagnosis. Those who used home health services were categorized as having mild disability (34.5%), moderate disability (32.1%), and severe disability (33.3%).

Patients with moderate disability at assessment had similar receipt of MM-directed therapy as those with mild disability and similar health care usage after diagnosis as patients with severe disability. 

These individuals have greater early mortality than older adults with MM who did not previously receive [home health] services, potentially highlighting the utility of [home health] service receipt as a marker of individuals who will need more intensive support when starting therapy.

Patients who used home health services had a higher comorbidity burden (3 vs 2) and higher mortality (adjusted risk ratio [RR] for 3-year mortality, 1.59; 95% CI, 1.55-1.64) than those who did not use these services. Postdiagnosis mortality was higher among those with more severe functional disability before diagnosis (adjusted RR at 6-months: severe vs mild, 2.30; 95% CI, 2.05-2.58; moderate vs mild, 1.32; 95% CI, 1.22-1.43).

“These individuals [requiring home health services] have greater early mortality than older adults with MM who did not previously receive [home health] services, potentially highlighting the utility of [home health] service receipt as a marker of individuals who will need more intensive support when starting therapy,” the authors wrote. 

Limitations of the study included its retrospective nature, lack of distinction between individuals with clinically overt MM and those with presymptomatic smoldering MM, and assessment of newly diagnosed patients potentially receiving first-line therapy.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.  

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Recent Publications

Detecting bone marrow infiltration in nonosteolytic multiple myeloma through separation of hydroxyapatite via the two-material decomposition technique in spectral computed tomography

Quant Imaging Med Surg. 2024 Mar 15;14(3):2345-2356. doi: 10.21037/qims-23-1042. Epub 2024 Mar 4. ABSTRACT BACKGROUND: Conventional computed tomography (CT) has low sensitivity for the diagnosis of bone marrow infiltration in nonosteolytic multiple myeloma (NOL-MM). This study aimed to compare the...