Follicular lymphoma in Sweden: nationwide improved survival in the rituximab era, particularly in elderly women: a Swedish Lymphoma Registry Study

Junlén, Henna Riikka; Peterson, Stefan; Kimby, Eva; Lockmer, Sandra; Lindén, Ola; Nilsson‐Ehle, Herman; Erlanson, Martin; Hagberg, Hans; Rådlund, A; Hagberg, Oskar; Wahlin, Björn Engelbrekt

doi:10.1038/leu.2014.251

Cited by 110 publications

(118 citation statements)

References 43 publications

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“…In DLBCL, FL, and CLL, all case incidence rates per 100,000 population were 3.81 (95% confidence interval 3.73–3.89), 2.18 (2.12–2.24), and 4.92 (4.83–5.01), respectively [47]. To calculate weightings in our model, we assumed thatThe percentage of incident patients treated with RTX was 95% for DLBCL [48, 49], 80% for FL [50], and 78% for CLL [51]. …”

Section: Methodsmentioning

confidence: 99%

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The Rituximab Biosimilar CT-P10 in Rheumatology and Cancer: A Budget Impact Analysis in 28 European Countries

et al. 2017

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IntroductionNew biosimilars of monoclonal antibodies are anticipated to bring significant cost savings and increase access to treatment. The rituximab biosimilar CT-P10 has recently been approved in Europe in all indications held by reference rituximab (RTX), including rheumatoid arthritis, non-Hodgkin’s lymphoma, and chronic lymphocytic leukemia. We analyzed the budgetary impact of the introduction of CT-P10 into the European Union (EU) for use in patients with rheumatoid arthritis and cancer diagnoses, using a budget impact analysis model.MethodsThe model used a base case scenario in which the 1-year uptake of CT-P10 was estimated at 30%, and the cost of CT-P10 was assumed to be 70% of the cost of RTX. A second 1-year scenario was also modeled, in which the market share of CT-P10 was assumed to be 50% (scenario 2). Finally, 3-year time horizon outcomes were calculated, in which the market share of CT-P10 was assumed to be 30%, 40%, and 50% in the first, second, and third years, respectively.ResultsIn the base case scenario, the introduction of CT-P10 was associated with projected savings of €90.04 million in the first year, which would allow 7531 additional patients to access rituximab treatment. This was equivalent to a 6.4% increase in the number of rituximab-treated patients. In scenario 2, budget savings were €150.10 million, with a total of 12,551 additional patients able to access rituximab, equivalent to a 10.7% increase. Over a 3-year time horizon, projected budget savings were approximately €570 million, equating to 47,695 additional patients able to access rituximab.ConclusionsThe model predicted that the introduction of CT-P10 in the EU will be associated with significant budget savings, the reallocation of which will enable many more patients to access rituximab treatment. This is likely to have a significant impact on health gains at patient and societal levels. Funding: CELLTRION Healthcare Co., Ltd. sponsored the development and analysis of the budget impact analysis model.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-017-0522-y) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

“…The percentage of incident patients treated with RTX was 95% for DLBCL [48, 49], 80% for FL [50], and 78% for CLL [51]. …”

Section: Methodsmentioning

confidence: 99%

The Rituximab Biosimilar CT-P10 in Rheumatology and Cancer: A Budget Impact Analysis in 28 European Countries

et al. 2017

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“…Patient outcomes are favorable, with median overall survival extending well beyond 10 y [3–5]. However, FL remains an incurable malignancy as most patients eventually experience progressive disease.…”

Section: Introductionmentioning

confidence: 99%

Histological Transformation and Progression in Follicular Lymphoma: A Clonal Evolution Study

et al. 2016

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BackgroundFollicular lymphoma (FL) is an indolent, yet incurable B cell malignancy. A subset of patients experience an increased mortality rate driven by two distinct clinical end points: histological transformation and early progression after immunochemotherapy. The nature of tumor clonal dynamics leading to these clinical end points is poorly understood, and previously determined genetic alterations do not explain the majority of transformed cases or accurately predict early progressive disease. We contend that detailed knowledge of the expansion patterns of specific cell populations plus their associated mutations would provide insight into therapeutic strategies and disease biology over the time course of FL clinical histories.Methods and FindingsUsing a combination of whole genome sequencing, targeted deep sequencing, and digital droplet PCR on matched diagnostic and relapse specimens, we deciphered the constituent clonal populations in 15 transformation cases and 6 progression cases, and measured the change in clonal population abundance over time. We observed widely divergent patterns of clonal dynamics in transformed cases relative to progressed cases. Transformation specimens were generally composed of clones that were rare or absent in diagnostic specimens, consistent with dramatic clonal expansions that came to dominate the transformation specimens. This pattern was independent of time to transformation and treatment modality. By contrast, early progression specimens were composed of clones that were already present in the diagnostic specimens and exhibited only moderate clonal dynamics, even in the presence of immunochemotherapy. Analysis of somatic mutations impacting 94 genes was undertaken in an extension cohort consisting of 395 samples from 277 patients in order to decipher disrupted biology in the two clinical end points. We found 12 genes that were more commonly mutated in transformed samples than in the preceding FL tumors, including TP53, B2M, CCND3, GNA13, S1PR2, and P2RY8. Moreover, ten genes were more commonly mutated in diagnostic specimens of patients with early progression, including TP53, BTG1, MKI67, and XBP1.ConclusionsOur results illuminate contrasting modes of evolution shaping the clinical histories of transformation and progression. They have implications for interpretation of evolutionary dynamics in the context of treatment-induced selective pressures, and indicate that transformation and progression will require different clinical management strategies.

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“…[1][2][3] However, outcomes are heterogeneous and a fraction of patients are at risk of early relapse/progression. Histologic transformation to aggressive lymphoma occurs in 2% to 3% of patients per year and is associated with treatment resistance, progression, and lymphoma-related mortality.…”

Section: Introductionmentioning

confidence: 99%

Cell of origin of transformed follicular lymphoma

Kridel

Mottok

Farinha

et al. 2015

Blood

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Key Points• TFL is most commonly of the germinal center B-cell-like phenotype, but a significant minority of cases is of the ABC phenotype (16%).• The absence of BCL2 translocation in FL at diagnosis is associated with transformation into ABC-like large cell lymphoma.Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell-like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell-like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL. (Blood. 2015;126(18):2118-2127

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Follicular lymphoma in Sweden: nationwide improved survival in the rituximab era, particularly in elderly women: a Swedish Lymphoma Registry Study

Cited by 110 publications

References 43 publications

The Rituximab Biosimilar CT-P10 in Rheumatology and Cancer: A Budget Impact Analysis in 28 European Countries

The Rituximab Biosimilar CT-P10 in Rheumatology and Cancer: A Budget Impact Analysis in 28 European Countries

Histological Transformation and Progression in Follicular Lymphoma: A Clonal Evolution Study

Cell of origin of transformed follicular lymphoma

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