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Source: Pharmacy Times articles

In addition to emerging treatment options, the speakers addressed the importance of individualized decision-making when treating patients with multiple myeloma.
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Source: Myeloma – Hematology Advisor

(HealthDay News) — A recently developed multivariable model can accurately predict smoldering multiple myeloma (SMM) or worse in persons with presumed monoclonal gammopathy of undetermined significance (MGUS), according to a study published online April 2 in the Annals of Internal Medicine.

Elias Eythorsson, M.D., Ph.D., from the University of Iceland in Reykjavik, and colleagues developed a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10 percent or greater bone marrow plasma cells (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample. In addition, performance of the prediction model was compared to performance of the Mayo Clinic risk stratification model. The study included 1,043 adults with immunoglobulin G (IgG), IgA, light-chain, and biclonal MGUS and an interpretable bone marrow sample.

The researchers found that the C-statistic was 0.85 for SMM or worse, and calibration was excellent. Sensitivity and specificity were 86 and 67 percent, respectively, at a threshold of 10 percent predicted risk for SMM or worse; positive and negative predictive values were 32 and 96 percent, respectively. Across a range of plausible low-risk thresholds, the net benefit for the decision to refer for sampling was 0.13 to 0.30 higher compared with the Mayo Clinic model.

“Persons with predicted risks below the relevant low-risk threshold could safely defer bone marrow sampling and be managed by primary care physicians as presumed MGUS,” the authors write.

Abstract/Full Text (subscription or payment may be required)

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Source: Myeloma – Hematology Advisor

The Food and Drug Administration (FDA) has approved Carvykti® (ciltacabtagene autoleucel) for the treatment of adults with relapsed or refractory multiple myeloma (MM) after at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. Previously, the treatment was only approved for relapsed or refractory MM after 4 or more prior lines of therapy.

Carvykti is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Upon binding BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.

The approval was based on data from the randomized, open-label, phase 3 CARTITUDE-4 study (ClinicalTrials.gov Identifier: NCT04181827), which evaluated the efficacy and safety of Carvykti in 419 adults with relapsed and lenalidomide-refractory MM who previously received at least 1 prior line of therapy including a proteasome inhibitor and an immunomodulatory agent.

Study participants were randomly assigned 1:1 to receive either a sequence of apheresis, bridging therapy, lymphodepletion and Carvykti or the physician’s choice of standard therapy (daratumumab, pomalidomide and dexamethasone or bortezomib, pomalidomide and dexamethasone). The primary endpoint was progression free survival (PFS).

After a median follow-up of 15.9 months, the median PFS was 12 months (95% CI, 9.8-14) for the standard therapy arm and not evaluable (95% CI, 22.8-not evaluable [NE]) for the Carvykti arm (hazard ratio [HR], 0.41 [95% CI, 0.30-0.56]; P <.0001). The estimated PFS rate at 12 months was 75.9% (95% CI, 69.4-81.1) in the Carvykti arm and 49.5% (95% CI, 42.3-56.3) in the standard therapy arm. 

Results also showed an overall response rate of 84.6% (95% CI, 79.0-89.2) in the Carvykti arm and 67.8% (95% CI, 61.0-74.0) in the standard therapy arm (P <.0001). Among responders, 74.0% (95% CI, 67.5-79.9) of patients in the Carvykti arm achieved complete response or better vs 22.3% (95% CI, 16.8-28.5) in the standard therapy arm (P <.0001).

In patients who achieved partial response or better or in those who achieved complete response or better, the estimated median duration of response was not reached in the Carvykti arm and was 16.6 months (95% CI, 12.9-NE) in the standard therapy arm.

“Carvykti demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” said Binod Dhakal, MD, Associate Professor, Medical College of Wisconsin, Division of Hematology and Oncology and investigator on the CARTITUDE-4 study. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

Carvykti is supplied as a single dose for infusion containing a suspension of CAR-positive viable T cells in 1 infusion bag.

“We understand the urgency for patients in need of Carvykti, and we have been making considerable progress in increasing supply and availability in anticipation of this milestone approval,” said Tyrone Brewer, President, US Hematology, Johnson & Johnson Innovative Medicine. “We more than doubled manufacturing of Carvykti in 2023, we are striving to double again in 2024, and we will continue to invest in our capacity so we can provide this critical therapy to as many patients as possible.”

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Source: Myeloma – Hematology Advisor

A novel sequential treatment program comprising VRD (bortezomib, lenalidomide, dexamethasone) induction, autologous stem cell transplantation (ASCT), KRD (carfilzomib, lenalidomide, dexamethasone) consolidation, and lenalidomide maintenance is feasible with promising efficacy in patients with newly diagnosed multiple myeloma (NDMM), according to research published in Cancer Science.

Investigators in Japan conducted a phase 2 clinical trial evaluating the safety and efficacy of the combined treatment strategy of 4 induction cycles with VRD, followed by bortezomib and high-dose melphalan with ASCT, 4 consolidation cycles with KRD, and lenalidomide maintenance until disease progression in patients with NDMM aged 20-65 years between 2017 and 2019. The primary endpoint was complete response (CR) rate following consolidation therapy with KRD.

The study included 141 patients (median age, 58 years; range, 36-65 years; 53.2% male). Most patients (83.7%) had a performance status of 0-1. Of patients available for cytogenetic analysis (n=121), 57.0% had high-risk cytogenetics and 17.4% had ultra-high-risk cytogenetics (≥2 high-risk cytogenetic abnormalities).

In the intent-to-treat population, a CR or better was achieved by 19.9% after induction, 39.7% after transplant, 58.9% after consolidation, and 62.4% after 1-year of maintenance therapy. At a median follow-up duration of 38 months, the 3-year progression-free survival (PFS) and overall survival rates were 83.5% and 92.5%, respectively. 

In patients with ultra-high-risk and high-risk cytogenetics, the 3-year PFS trended toward lower than that of patients without any high-risk cytogenetics (61.2% vs 77.8% vs 89.4%, respectively). 

Overall, treatment was discontinued in 22.0% patients due to unacceptable adverse events (AEs). Severe adverse events (grade ≥3) occurred in approximately 30% of patients. No treatment-related mortality occurred. 

“Our study showed an encouraging outcome, with responses consistently deepening throughout the program,” the authors wrote in their report. “Future studies should assess whether the innovative therapeutic strategy incorporating the anti-CD38 antibody increases protocol completion rates and thereby enhances survival outcomes, particularly in patients with high-risk or ultra-high-risk cytogenetics.”

Limitations of the study included the single-arm design and lack of control arm, inclusion of only Japanese patients, potential selection bias, and relatively small sample size.

Disclosure: This research was supported by ONO PHARMACEUTICAL CO. LTD. and Bristol Myers Squibb K.K. Please see the original reference for a full list of disclosures.

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Source: Myeloma – Hematology Advisor

The use of the Comprehensive Score for Financial Toxicity (COST) as a tool to standardize the measurement of financial toxicity among patients with cancer is increasing, but whether changes in COST score overtime is meaningful is not yet clear.

“For some patients, changes in COST score may be spurious and not rooted in meaningful changes in financial toxicity status,” the authors wrote in their report published in JCO Oncology Practice.

The study used a sequential mixed-methods approach, in which COST scores at 2 time points were collected 8 weeks apart from 72 patients with multiple myeloma (MM) as part of a quantitative assessment. Then a qualitative assessment was conducted with a subset of 12 patients with the largest change in COST scores, who participated in semistructured interviews.

The majority of patients demonstrated a change in COST score, with 38% demonstrating an improved score and 50% a worse score. The absolute change was a median of 4 points, with the first assessment demonstrating a median score of 25 and the second assessment a median of 22.5.

Intrapatient agreement was 50%. In addition, the majority of patients did not complete all items on the COST instrument at both assessments (3%).

Among the interviewed patients, 58% reported a change to at least 1 of the constructs of the financial toxicity conceptual model. Out-of-pocket medical costs were the most common change, occurring in 42% of cases, followed by nonmedical expenses in 17% and subjective financial burden in 17%.

Increases in out-of-pocket medical costs were the result of loss or reduction of financial assistance, a change in treatment, and increase in clinic visits. Decreases were a result of an increase in financial assistance and reduced frequency of treatment.

The authors identified areas where additional research regarding the use of the COST score is needed, including determining a meaningful cutoff for financial toxicity and that the instrument focuses on subjective questions.

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Source: Pharmacy Times articles

Venetoclax, which is approved for leukemia, blocks a function of the BCL-2 protein and has previously shown efficacy in a small proportion of patients with multiple myeloma.
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