Multicenter Retrospective Analysis of Clinical Characteristics, Treatment Patterns, and Outcomes in Very Elderly Patients with Diffuse Large B-Cell Lymphoma: The Korean Cancer Study Group LY16-01

Choi, Jung Hye; Kim, Tae Min; Kim, Hyo Jung; Koh, Sung Ae; Mun, Yeung Chul; Kang, Hye Jin; Jung, Yun Hwa; Shim, Hyeok; Chong, So Young; Sun, Der Sheng; Lee, Soonil; Park, Byeong Bae; Kwon, Jung Hye; Nam, Seung Hyun; Yi, Jun; Yuh, Young Jin; Jin, Jong Youl; Han, Ji Sang; Kim, Seok Hyun

doi:10.4143/crt.2017.172

Cited by 9 publications

(8 citation statements)

References 16 publications

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“…The occurrence of serious adverse events in an older (≥75 years) DLBCL population receiving R-CHOP therapy, led by hematologic toxicities and infections, offset the efficacy of such therapy in this older population [40]. The significance of treatment-related toxicities as myelosuppression and infections impacting the delivery of R-CHOP therapy ≥70 years of age has been noted in other series [26,37,42]. However, in a large series of patients ≥60 years of age who received initial R-CHOP-14 or −21, high delivered dose intensities were noted, with three-year OS of 76% [43].…”

Section: Discussionmentioning

confidence: 96%

“…Although the International Prognostic Index (IPI) utilized an age cutoff of 60 years in the pre-rituximab era, more recent findings have suggested that age 70 years may be of greater prognostic value based upon post-rituximab era data [35,36]. Series of very old DLBCL patients are limited [31,[37][38][39][40]. In one series of 207 patients (median age 83 years), three-year OS was 54%, with longer failure-free survival with R-CHOP or R-EPOCH therapy as compared to regimens as R-CVP or R-CEOP [31].…”

Section: Discussionmentioning

confidence: 99%

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Treatment approaches for older and oldest patients with diffuse large B-cell lymphoma – Use of non-R-CHOP alternative therapies and impact of comorbidities on treatment choices and outcome: A Humedica database retrospective cohort analysis, 2007–2015

Morrison

Hamilton²,

Ogbonnaya³

et al. 2020

Journal of Geriatric Oncology

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a b s t r a c tIntroduction: We characterized real-world treatment patterns in older (65-74 years) and oldest (75-85 years) patients with diffuse large B-cell lymphoma (DLBCL) receiving initial therapy (R-CHOP, non-R-CHOP regimens). Impact of comorbidities on treatment choice, and overall and progression-free survival (OS, PFS) were assessed by age. Patients and Methods: Using the Humedica database, we identified 1436 newly diagnosed patients with DLBCL who received frontline therapy from 1/07-9/15. The 885 patients ≥65 years of age were further evaluated for baseline demographics, comorbidities, initial therapy, and PFS/OS. Results: Of 885 patients, 406 (45.9%) were age 65-74, and 479 (54.1%) age 75-85, years. First line therapy was R-CHOP (61.8%) or non-R-CHOP (38.2%). Although Charlson Comorbidity Index (CCI) scores were similar at baseline, congestive heart failure and myocardial infarction were more common in those receiving non-R-CHOP regimens. Survival outcomes were superior for those receiving initial R-CHOP, versus non-R-CHOP, therapy (median PFS 53.9 versus 27.8 months; two-year PFS 71.2% versus 51.6%, p b .0001; median OS not reached versus 45 months; two-year OS 81.3% versus 62.9%, p b .0001, respectively). Only 10.4% (R-CHOP) and 12.1% (non-R-CHOP) of patients received second line therapies. Two-year OS by age (65-74, 75-85 years) was 66.4% and 39.1%, respectively with R-CHOP (p = .0045), and 74.3% and 54.5%, respectively with non-R-CHOP (p = .004), therapy. Age ≥ 75 years and CCI of 2+ were associated with shorter OS and PFS. Conclusions: This study identified real-world first line treatment patterns for older patients with DLBCL. Our findings support the feasibility of administering standard R-CHOP therapy, even to oldest patients with DLBCL.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Treatment approaches for older and oldest patients with diffuse large B-cell lymphoma – Use of non-R-CHOP alternative therapies and impact of comorbidities on treatment choices and outcome: A Humedica database retrospective cohort analysis, 2007–2015

Morrison

Hamilton²,

Ogbonnaya³

et al. 2020

Journal of Geriatric Oncology

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“… 13 , 24 , 25 , 26 , 27 Hypoalbuminaemia is a predictive factor for shorter survival, decreased relative dose intensity of anthracycline and cyclophosphamide, and increased risk of TRM. 28 , 29 , 30 , 31 , 32 High NLR is also correlated with shorter survival, lower CR rate, advanced stage, higher LDH level, and increased risk of depression. 32 , 33 , 34 , 35 , 36 , 37 The CXI comprehensively assesses these clinical parameters, and therefore may more effectively overcome the bias caused by confounding factors affecting the clinical outcomes of the patients than any single parameter of cancer cachexia.…”

Section: Discussionmentioning

confidence: 98%

“…Sarcopenia is associated with shorter survival, reduced response to treatment, increased treatment‐related toxicities, frequent dose reduction, and early termination of treatment 13,24–27 . Hypoalbuminaemia is a predictive factor for shorter survival, decreased relative dose intensity of anthracycline and cyclophosphamide, and increased risk of TRM 28–32 . High NLR is also correlated with shorter survival, lower CR rate, advanced stage, higher LDH level, and increased risk of depression 32–37 .…”

Section: Discussionmentioning

confidence: 99%

Cachexia index as a potential biomarker for cancer cachexia and a prognostic indicator in diffuse large B‐cell lymphoma

Park

et al. 2021

J cachexia sarcopenia muscle

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Background Cancer cachexia is known to adversely affect the clinical course in patients with malignant lymphoma. The cachexia index (CXI) is a potential biomarker of cancer cachexia, and its implications for the prognosis and treatment outcome of lung cancer and aggressive lymphoma has been assessed in previous studies. Methods A total of 267 patients diagnosed with diffuse large B‐cell lymphoma who were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) immunochemotherapy were retrospectively reviewed. The CXI was calculated as the skeletal muscle index (SMI) × serum albumin/neutrophil–lymphocyte ratio (NLR). Although previous studies measured the SMI using the muscles of the L3 vertebral level, the present study used both the L3 vertebral muscles and the pectoralis muscles (PM) at the T4 vertebral level to measure the SMI. Depending on the type of muscles used, the CXI was termed the L3‐CXI or PM‐CXI. Using sex‐specific cutoff values for CXI, the patients were categorized as follows: (i) high‐CXI group (high L3‐CXI and high PM‐CXI), (ii) intermediate‐CXI group (high L3‐CXI and low PM‐CXI), and (iii) low‐CXI group (low L3‐CXI and low PM‐CXI). Results Complete responses to R‐CHOP were obtained in 145/173 (83.8%), 25/36 (69.4%), and 27/57 (47.4%) patients in the high‐CXI, intermediate‐CXI, and low‐CXI groups, respectively (P < 0.001). Treatment‐related anaemia (15.6%, 30.6%, and 26.3%, P = 0.038), thrombocytopenia (21.4%, 36.1%, and 43.9%, P < 0.001), febrile neutropenia (23.7%, 44.4%, and 36.8%, P = 0.022), and any nonhaematologic toxicity (31.2%, 44.4%, and 54.4%, P = 0.001) of Grade 3 or more were more common in the lower CXI groups than in the higher‐CXI groups. Early treatment discontinuation for reasons other than lymphoma progression also occurred more frequently in the low‐CXI group (24/57, 42.1%) compared with the intermediate‐CXI (5/36, 13.9%) and high‐CXI (18/173, 10.4%) groups (P < 0.001). Median overall survival in the high‐CXI, intermediate‐CXI, and low‐CXI groups was not reached, 50.6 months, and 14.5 months, respectively (p < 0.001). Multivariable analysis showed that low CXI was an independent negative prognostic factor for overall survival (hazard ratio 2.103, 95% confidence interval 1.278–3.460, P = 0.003). Conclusions We suggest that in patients with diffuse large B‐cell lymphoma, the CXI is a biomarker for cancer cachexia that can predict survival, treatment response, treatment‐related toxicity, and compliance with R‐CHOP. Patients were more clearly stratified by this new CXI category compared with the classifications described in previous studies.

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“…The four selected risk features have also consistently been found to be independently associated with reduced OS in DLBCL. [22][23][24][25] Although further research is certainly warranted, these reports further underpin the predictor selection proposed in this analysis.…”

Section: Discussionmentioning

confidence: 80%

TRAIL Score: A Simple Model to Predict Immunochemotherapy Tolerability in Patients With Diffuse Large B-Cell Lymphoma

Harris¹,

Bataillard

Choi³

et al. 2022

JCO Clinical Cancer Informatics

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PURPOSE Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) represents the standard of care for first-line treatment of diffuse large B-cell lymphoma (DLBCL). However, many patients are unable to tolerate R-CHOP and have inferior outcomes. This study aimed to develop a practical tool to help physicians identify patients with newly diagnosed DLBCL unlikely to tolerate a full course of R-CHOP. METHODS We developed a predictive model (Tolerability of R-CHOP in Aggressive Lymphoma [TRAIL]) on the basis of a training data set from the phase III GOYA trial (obinutuzumab with CHOP v R-CHOP in 1L DLBCL) using a composite binary end point, identifying patients who prematurely stopped or required reductions of R-CHOP. Candidate predictive variables were selected on the basis of known baseline characteristics that contribute to patient frailty, comorbidity, and/or chemotherapy toxicity. TRAIL was developed using an iterative trial-and-error modeling process to fit a logistic regression model. The final model was evaluated for robustness using a GOYA holdout data set and the phase III MAIN (R-CHOP with or without bevacizumab in 1L DLBCL) R-CHOP-21 data set as external validation. RESULTS TRAIL includes four simple predictors available in the routine clinical setting: Charlson Comorbidity Index, presence of cardiovascular disease or diabetes, serum albumin, and creatinine clearance. Model generalization performance estimated by the area under the curve was around or above 0.70 across GOYA training, GOYA holdout, and MAIN data sets. Classifying patients into low-, intermediate- and high-risk categories, the proportion of patients experiencing a tolerability event was 3.3%, 12.4%, and 32.9%, respectively, in GOYA holdout, and 9.7%, 9.7%, and 34.2%, respectively, in MAIN. CONCLUSION TRAIL may be useful as a clinical decision support tool for treatment decisions in patients with DLBCL who may not tolerate standard chemoimmunotherapies.

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Multicenter Retrospective Analysis of Clinical Characteristics, Treatment Patterns, and Outcomes in Very Elderly Patients with Diffuse Large B-Cell Lymphoma: The Korean Cancer Study Group LY16-01

Cited by 9 publications

References 16 publications

Treatment approaches for older and oldest patients with diffuse large B-cell lymphoma – Use of non-R-CHOP alternative therapies and impact of comorbidities on treatment choices and outcome: A Humedica database retrospective cohort analysis, 2007–2015

Treatment approaches for older and oldest patients with diffuse large B-cell lymphoma – Use of non-R-CHOP alternative therapies and impact of comorbidities on treatment choices and outcome: A Humedica database retrospective cohort analysis, 2007–2015

Cachexia index as a potential biomarker for cancer cachexia and a prognostic indicator in diffuse large B‐cell lymphoma

TRAIL Score: A Simple Model to Predict Immunochemotherapy Tolerability in Patients With Diffuse Large B-Cell Lymphoma

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