A simplified frailty score predicts survival and can aid treatment-intensity decisions in older patients with DLBCL

Isaksen, Kathrine T.; Mastroianni, Maria Adele; Rinde, Marit; Rusten, Leiv S.; Barzenje, Dlawer Abdulla; Ramslien, Lloyd Frode; Slaaen, Marit; Jerm, Marianne Brenn; Smeland, Erlend B.; Rostoft, Siri; Liestøl, Knut; Brodtkorb, Marianne; Holte, Harald

doi:10.1182/bloodadvances.2021004777

Cited by 16 publications

(23 citation statements)

References 53 publications

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“…In particular, the GPI identified a large low-risk group with a very favorable prognosis (GPI low-risk group: 33% of patients, 95% 2-year OS versus IPI low risk group: 24% of patients, 85% 2-year OS) (Table 4). The predictive value of the GPI also exceeded that of our previously developed frailty score 19 (C-index 0.64).…”

Section: External Validation Of the Gpi And Comparison With Ipi R-ipi...mentioning

confidence: 60%

“…Before start of treatment, we and others suggest to assess frailty status by an objective GA to help evaluate patients' fitness for R-CHOP treatment. [16][17][18][19]21 Alternatives for frailty assessment include our previously proposed frailty score that is easily accessible together with the GPI in an online calculator. 19 Of note, frailty status should be re-evaluated after pre-phase treatment to allow for improvement in frailty status for patients with reduced fitness mainly caused by their lymphoma.…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15][16][17][18] A full GA is resource demanding and we and others have shown that a simplified GA can readily and precisely predict survival in older DLBCL patients. [19][20][21] Here, we aimed to develop and externally validate a clinical prediction model especially suited for older (≥ 70 years) DLBCL patients who are considered candidates for curative treatment. For this purpose, we used a population-based, R-CHOP-treated cohort to examine candidate predictors of special importance in older patients including GA variables, in addition to established lymphoma predictors and routine tumor markers.…”

Section: Introductionmentioning

confidence: 99%

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The Geriatric Prognostic Index: a clinical prediction model for survival of older diffuse large B-cell lymphoma patients treated with standard immunochemotherapy

Isaksen¹,

Galleberg²,

Mastroianni³

et al. 2023

haematol

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International prognostic Index (IPI) is the most widely used clinical prediction model for diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), but may be suboptimal in older patients. We aimed to develop and externally validate a clinical prediction model for older, R-CHOP treated DLBCL patients by examining geriatric assessment and lymphoma-related parameters in real-world cohorts. A population-based training set of 365 R-CHOP treated DLBCL patients ≥70 years was identified through the Cancer Registry of Norway. The external test set consisted of a population-based cohort of 193 patients. Data on candidate predictors was retrieved from the Cancer Registry and through review of clinical records. Cox regression models for 2-year overall survival (OS) were used for model selection. Activities of daily living (ADL), Charlson Comorbidity index (CCI), age, sex, albumin, stage, ECOG and LDH were identified as independent predictors and combined into a Geriatric prognostic index (GPI). The GPI demonstrated good discrimination (optimism-corrected C-index 0.752), and identified a low-, intermediate- and high-risk group with significantly different survival (2-year OS 94%, 65%, 25%). At external validation, the continuous and grouped GPI demonstrated good discrimination (C-index 0.727, 0.710) and the GPI groups had significantly different survival (2- year OS 95%, 65%, 44%). Both the continuous and grouped GPI showed better discrimination than IPI, R-IPI and NCCN-IPI (C-index 0.621, 0.583, 0.670) We have developed and externally validated the GPI for older DLBCL patients treated with RCHOP that outperformed IPI, R-IPI and NCCN-IPI. A web-based calculator is available at https://wide.shinyapps.io/GPIcalculator/.

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Section: External Validation Of the Gpi And Comparison With Ipi R-ipi...mentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Geriatric Prognostic Index: a clinical prediction model for survival of older diffuse large B-cell lymphoma patients treated with standard immunochemotherapy

Isaksen¹,

Galleberg²,

Mastroianni³

et al. 2023

haematol

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“…In 62% of R-CHOP-treated patients aged 85–89 yr, and 2 patients aged ≥90 yr, ≥6 cycles were given. However, our methodology could not discriminate R-CHOP from R-miniCHOP, the preferred regimen in patients ≥80 years old ( 46 , 47 ).…”

Section: Resultsmentioning

confidence: 78%

Real-World Estimation of First- and Second-Line Treatments for Diffuse Large B-Cell Lymphoma Using Health Insurance Data: A Belgian Population-Based Study

Daneels

Rosskamp²,

Macq³

et al. 2022

Front. Oncol.

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We determined first- and second-line regimens, including hematopoietic stem cell transplantations, in all diffuse large B cell lymphoma (DLBCL) patients aged ≥20 yr (n = 1,888), registered at the Belgian Cancer Registry (2013–2015). Treatments were inferred from reimbursed drugs, and procedures registered in national health insurance databases. This real-world population-based study allows to assess patients usually excluded from clinical trials such as those with comorbidities, other malignancies (12%), and advanced age (28% are ≥80 yr old). Our data show that the majority of older patients are still started on first-line regimens with curative intent and a substantial proportion of them benefit from this approach. First-line treatments included full R-CHOP (44%), “incomplete” (R-)CHOP (18%), other anthracycline (14%), non-anthracycline (9%), only radiotherapy (3%), and no chemo-/radiotherapy (13%), with significant variation between age groups. The 5-year overall survival (OS) of all patients was 56% with a clear influence of age (78% [20–59 yr] versus 16% [≥85 yr]) and of the type of first-line treatments: full R-CHOP (72%), other anthracycline (58%), “incomplete” (R-)CHOP (47%), non-anthracycline (30%), only radiotherapy (30%), and no chemo-/radiotherapy (9%). Second-line therapy, presumed for refractory (7%) or relapsed disease (9%), was initiated in 252 patients (16%) and was predominantly (71%) platinum-based. The 5-year OS after second-line treatment without autologous stem cell transplantation (ASCT) was generally poor (11% in ≥70 yr versus 17% in <70 yr). An ASCT was performed in 5% of treated patients (n = 82). The 5-year OS after first- or second-line ASCT was similar (69% versus 66%). After adjustment, multivariable OS analyses indicated a significant hazard ratio (HR) for, among others, age (HR 1.81 to 5.95 for increasing age), performance status (PS) (HR 4.56 for PS >1 within 3 months from incidence), subsequent malignancies (HR 2.50), prior malignancies (HR 1.34), respiratory and diabetic comorbidity (HR 1.41 and 1.24), gender (HR 1.25 for males), and first-line treatment with full R-CHOP (HR 0.41) or other anthracycline-containing regimens (HR 0.72). Despite inherent limitations, patterns of care in DLBCL could be determined using an innovative approach based on Belgian health insurance data.

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“…Indeed, the benefits of this strategy in DLBCL have been extensively studied by different groups. 19 , 20 …”

Section: Discussionmentioning

confidence: 99%

Prognostic Stratification of Diffuse Large B-cell Lymphoma Using Clinico-genomic Models: Validation and Improvement of the LymForest-25 Model

Orgueira¹,

Arias

López³

et al. 2022

HemaSphere

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Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Despite notable therapeutic advances in the last decades, 30%–40% of affected patients develop relapsed or refractory disease that frequently precludes an infamous outcome. With the advent of new therapeutic options, it becomes necessary to predict responses to the standard treatment based on rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). In a recent communication, we presented a new machine learning model (LymForest-25) that was based on 25 clinical, biochemical, and gene expression variables. LymForest-25 achieved high survival prediction accuracy in patients with DLBCL treated with upfront immunochemotherapy. In this study, we aimed to evaluate the performance of the different features that compose LymForest-25 in a new UK-based cohort, which contained 481 patients treated with upfront R-CHOP for whom clinical, biochemical and gene expression information for 17 out of 19 transcripts were available. Additionally, we explored potential improvements based on the integration of other gene expression signatures and mutational clusters. The validity of the LymForest-25 gene expression signature was confirmed, and indeed it achieved a substantially greater precision in the estimation of mortality at 6 months and 1, 2, and 5 years compared with the cell-of-origin (COO) plus molecular high-grade (MHG) classification. Indeed, this signature was predictive of survival within the MHG and all COO subgroups, with a particularly high accuracy in the “unclassified” group. Integration of this signature with the International Prognostic Index (IPI) score provided the best survival predictions. However, the increased performance of molecular models with the IPI score was almost exclusively restricted to younger patients (<70 y). Finally, we observed a tendency towards an improved performance by combining LymForest-25 with the LymphGen mutation-based classification. In summary, we have validated the predictive capacity of LymForest-25 and expanded the potential for improvement with mutation-based prognostic classifications.

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A simplified frailty score predicts survival and can aid treatment-intensity decisions in older patients with DLBCL

Cited by 16 publications

References 53 publications

The Geriatric Prognostic Index: a clinical prediction model for survival of older diffuse large B-cell lymphoma patients treated with standard immunochemotherapy

The Geriatric Prognostic Index: a clinical prediction model for survival of older diffuse large B-cell lymphoma patients treated with standard immunochemotherapy

Real-World Estimation of First- and Second-Line Treatments for Diffuse Large B-Cell Lymphoma Using Health Insurance Data: A Belgian Population-Based Study

Prognostic Stratification of Diffuse Large B-cell Lymphoma Using Clinico-genomic Models: Validation and Improvement of the LymForest-25 Model

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