The impacts of initial and relative dose intensity of R-CHOP on outcomes of elderly patients with diffuse large B-cell lymphoma

Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Tamura, Miho; Sawada, Takeshi; Omuro, Yasushi; Hishima, Tsunekazu; Maeda, Yoshiharu

doi:10.1080/10428194.2016.1211279

Cited by 13 publications

(16 citation statements)

References 13 publications

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“…To the best of our knowledge, this is the first report to evaluate between RDI and the clinical outcome in patients with advanced‐stage FL treated R‐CHOP. Several studies have found a correlation between the RDI of R‐CHOP and the clinical outcomes of diffuse large B‐cell lymphoma . However, in this study, we found no significant impact of RDI on patient outcomes in advanced‐stage FL.…”

Section: Baseline Patients' Characteristicscontrasting

confidence: 87%

“…Several studies have found a correlation between the RDI of R-CHOP and the clinical outcomes of diffuse large B-cell lymphoma. [10][11][12][13] However, in this study, we found no significant impact explanation is that patients with low tumor burden (who might be candidates for "watch and wait" strategy) were included.…”

mentioning

confidence: 86%

“…The median value of RDI was 0.72 (range, 0.21‐1.05), and the mean was 0.69. We defined the appropriate cut‐off point of the RDI as 0.7 using receiver operating characteristic curve (area under the curve 0.61, 95% CI 0.45‐0.77) and from previous studies evaluating the impact of RDI in diffuse large B‐cell lymphoma patients . We investigated the PFS and OS of patients stratified into two groups: low‐intensity (RDI < 0.7, n = 41) and high‐intensity (RDI ≥ 0.7, n = 53) group.…”

Section: Baseline Patients' Characteristicsmentioning

confidence: 99%

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Relative dose intensity of R‐CHOP therapy and patient outcomes in advanced follicular lymphoma

Konishi

Kanemasa

Sasaki

et al. 2019

Hematological Oncology

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Section: Baseline Patients' Characteristicscontrasting

confidence: 87%

mentioning

confidence: 86%

Section: Baseline Patients' Characteristicsmentioning

confidence: 99%

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Relative dose intensity of R‐CHOP therapy and patient outcomes in advanced follicular lymphoma

Konishi

Kanemasa

Sasaki

et al. 2019

Hematological Oncology

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“…However, the results of the retrospective study showed that older patients aged 70‐80 years who were treated with full treatment doses had better prognoses than patients with treatment attenuation; not all elderly patients are sufficiently healthy to tolerate the full‐dose treatment . The analysis of 479 de novo DLBCL patients aged 70‐79 years who were treated with R‐CHOP demonstrated that maintenance of the RDI was associated with improved outcome of elderly patients with DLBCL, suggesting that maintaining an RDI with adequate dose reduction is more important than uniformly administering a full dose of R‐CHOP to elderly patients …”

Section: Discussionmentioning

confidence: 99%

The average relative dose intensity of R‐CHOP is an independent factor determining favorable overall survival in diffuse large B‐cell lymphoma patients

Długosz‐Danecka

Szmit²,

Ogórka

et al. 2019

Cancer Medicine

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The prognosis of diffuse large B‐cell lymphoma (DLBCL) patients depends on lymphoma‐ and patient‐related risk factors and is best estimated by the international prognostic index (IPI). The aim of the study was to determine whether the average relative dose intensity (ARDI) of an anthracycline‐containing regimen could predict DLBCL outcome independently from the IPI. We analyzed 223 white Caucasian DLBCL patients who completed at least four cycles of first‐line immunochemotherapy with rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R‐CHOP). The ARDI was calculated by specially developed software in each individual patient, simultaneously with the chemotherapy prescription, which instantly revealed all causes of its decrease. The relevance of the ARDI for progression‐free/overall survival (PFS/OS) was evaluated. Prolonged intervals between cycles of immunochemotherapy—the most common cause of decreased ARDI (49.3%, 110/223)—were due to neutropenia (absolute neutrophil count <1.0 × 109/L) and infections. Reductions in cytostatic doses were observed in 19.7% (44/223) of patients, mainly as the consequence of cardiotoxicity (23/223, 10.3%). The OS varied significantly when the ARDI was >90% (P < 0.00001). Multivariate analysis confirmed that an ARDI>90% was an IPI‐independent predictor of prolonged PFS (HR = 0.31; 95%CI: 0.20‐0.47; P < 0.00001) and OS (HR = 0.32; 95%CI: 0.21‐0.48; P < 0.00001). With an analytic tool allowing real‐time ARDI assessment, it was possible to maintain an ARDI above 90% in 161 of 223 patients (72%). DLBCL patients with an ARDI >90% have significantly better outcome regardless of the IPI; therefore, our official recommendation is an adequate dose density through efficient neutropenia prophylaxis and cardiac protection.

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“…As far as treatment delays, there was no significant difference between younger and older patients, though we do not have data regarding dose reductions. Prior studies have shown that primary changes in relative dose intensity, or the amount of drug delivered per unit of time, is affected by both dose delays and reductions, and has been correlated with worse outcomes in breast cancer, colon cancer, and NHL [16–18]. Several retrospective studies in older patients with large cell lymphoma have shown a correlation between reduced dose intensity of cyclophosphamide and/or anthracycline and inferior OS [19–23], though RDI has also been correlated with advanced age, worse performance status, and multiple comorbidities, confounding any survival analysis.…”

Section: Discussionmentioning

confidence: 99%

Frequency and impact of grade three or four toxicities of novel agents on outcomes of older patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma (alliance A151611)

Tallarico

Foster

Seisler

et al. 2018

Journal of Geriatric Oncology

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Objective Older patients with cancer suffer from chemotherapy-related toxicities more frequently than younger patients. As novel agents are being used more commonly in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), toxicities of these agents in older patients have not been well studied. Further, impact of these toxicities on outcomes in the elderly is unknown. This study aimed to answer both questions. Patients and Methods We reviewed 14 Alliance for Clinical Trials in Oncology trials that enrolled CLL and/or NHL patients between 2004–2014. Toxicity was assessed per the NCI-CTCAE (version 3–5). Probabilities of experiencing grade three or four hematologic and non-hematologic toxicities were modeled as a function of clinical and disease-related factors using logistic regression. Results 1199 patients (409 age ≥ 65; 790 age < 65) were analyzed; 438 received only biologic therapy (145 age ≥ 65; 293 age < 65), and 761 received biologic + chemotherapy (264 age ≥ 65; 497 age < 65). The odds of grade three or four hematologic [odds ratio (OR) 1.70; p = 0.009: 95% CI (1.57–1.84)] and non-hematologic toxicities [OR 1.47; p = 0.022; 95% CI (1.39–1.55)] were increased in older patients with CLL, as well as odds of grade three or four non-hematologic toxicities [OR 1.89; p = 0.017; 95% CI (1.64–2.17)] in older patients with NHL. Grade three or four hematologic toxicities were associated with inferior OS and PFS in older patients with NHL [HR 3.14; p = 0.006; 95% CI (2.25–4.39) for OS and 3.06; p = 0.011; 95% CI (2.10–4.45) for PFS], though not in CLL. A prognostic model predicting grade three or four toxicities was also developed. Conclusions CLL and NHL patients ≥ 65 year encounter more toxicities than younger patients even when treated with novel biologic agents. Development of grade three or four hematologic toxicities lead to inferior PFS and OS in NHL but not in CLL.

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The impacts of initial and relative dose intensity of R-CHOP on outcomes of elderly patients with diffuse large B-cell lymphoma

Cited by 13 publications

References 13 publications

Relative dose intensity of R‐CHOP therapy and patient outcomes in advanced follicular lymphoma

Relative dose intensity of R‐CHOP therapy and patient outcomes in advanced follicular lymphoma

The average relative dose intensity of R‐CHOP is an independent factor determining favorable overall survival in diffuse large B‐cell lymphoma patients

Frequency and impact of grade three or four toxicities of novel agents on outcomes of older patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma (alliance A151611)

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