Impact of comorbidity and relative dose intensity on outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP

Yamamoto, Masakazu; Suzuki, Ikukatsu; Saitou, Kouji; Tsumanuma, Riko; Okuyama, Shuhei; Kumagai, Hiroaki; Omoto, Eijiro; Satoh, Shinji; Tajima, Katsushi

doi:10.1007/s00432-020-03279-7

Cited by 10 publications

(10 citation statements)

References 22 publications

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“…Early studies in NHL patients treated with an anthracycline-containing induction regimen showed that 28% of patients had an RDI <70%, which was associated with a decreased response rate and shorter overall 2-year survival [5]. Similar findings have been reported in more recent studies with the rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen, noting poor survival associated with RDI of less than 50-90% (Table 1) [47][48][49][50].…”

Section: Article Highlightssupporting

confidence: 63%

“…Differences in optimal RDI cutoff values have also been noted among NHL studies. Early observations suggested that RDI <70% was associated with poor outcomes [5]; however, among recent studies assessing RDI in patients treated with R-CHOP21, optimal RDI values were reported as 70%, 85%, and 90% [47,[49][50][51]. These variations may be due to differences in patient-or disease-specific characteristics among the cohorts, length of follow-up, or RDI calculation methods.…”

Section: Optimal Rdi Cutoff Valuesmentioning

confidence: 99%

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Prophylaxis and treatment strategies for optimizing chemotherapy relative dose intensity

Shayne

Harvey

Lyman

2021

Expert Review of Anticancer Therapy

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Introduction: A decrease in relative-dose intensity (RDI) of chemotherapy has been shown to be associated with poor patient outcomes in solid tumors and non-Hodgkin's lymphoma. The actual delivered chemotherapy dose received by patients can be influenced by dose reductions and treatment delays, often due to toxicities, most commonly chemotherapy-induced neutropenia (CIN). Areas covered: We review seminal evidence and more recent studies that have shown an association between higher RDI and improved patient survival. A smaller number of studies has shown no association between RDI and outcomes. These differences may be due to study limitations, including low power, differences in patient and disease characteristics, or the chemotherapeutic regimen. We describe guidelines recommendations to prevent and treat CIN with granulocyte-colony stimulating factor (G-CSF) and describe novel approaches to prevent neutropenia that are being developed that may provide greater value and be associated with fewer adverse events than standard G-CSF options. Expert opinion: Maintaining RDI is important to ensure optimal patient outcomes. This can be achieved through the proper administration of G-CSF prophylaxis and treatment. Newer agents in development to treat and/or prevent CIN are entering regulatory review and may potentially change the treatment landscape for CIN in the future.

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Section: Article Highlightssupporting

confidence: 63%

Section: Optimal Rdi Cutoff Valuesmentioning

confidence: 99%

Prophylaxis and treatment strategies for optimizing chemotherapy relative dose intensity

Shayne

Harvey

Lyman

2021

Expert Review of Anticancer Therapy

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“…We used multivariable logistic regression to examine the association between patient demographics and clinical factors and these binary outcomes of interest [18,19]. We first conducted univariate analyses to assess the association between patient demographic (age, sex, race, marital status) and clinical factors (ECOG performance status, comorbidity score; dichotomized to <2 versus ≥2 consistent with prior work) [11], advanced stage, hypoalbuminemia (defined as <3.5 g/dL consistent with prior work) [20], elevated LDH (≥250 U/L consistent with prior work) [21], diagnosis (DLBCL vs. all other histologies), treatment regimen (reduced-dose CHOP [mini-CHOP] with or without rituximab, CHOP with or without rituximab, EPOCH with or without rituximab, or other), and CNS prophylaxis (yes or no) with the binary outcomes of interest. We selected covariates a priori based on previous studies demonstrating that these covariates correlate with prognosis and/or rates of toxicities in aggressive NHL [22][23][24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes, Treatment Toxicity, and Health Care Utilization in Older Adults with Aggressive Non-Hodgkin Lymphoma

Johnson

Horick

et al. 2021

The Oncologist

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Background. Although balancing treatment efficacy with risks of complications is critical for older adults with aggressive non-Hodgkin lymphoma (NHL), few studies have described these patients' clinical outcomes, rates of toxicities, and health care utilization. Methods. We conducted a retrospective analysis of adults ≥65 years diagnosed with aggressive NHL and receiving systemic therapy at Massachusetts General Hospital from April 2000 to July 2020. We abstracted patient characteristics, clinical outcomes, treatment toxicity, unplanned hospitalizations, and intensive care unit (ICU) admissions within 6 months of treatment initiation from the medical record. Using multivariable logistic regression, we examined factors associated with rates of grade 3+ nonhematologic toxicity and unplanned hospitalization. Results. Among 295 patients (median age, 73 years; 39.0% female), 5-year overall survival (OS) was 74.2%. Five-year OS by age group (65-69, 70-74, 75-79, and 80+ years) was

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“…In the studies that evaluated time-dependent DI across all cycles, early discontinuation before completing the standard $6 cycles generally did not result in a reduced RDI. Four studies 9,13,15,18 reported that, in case of premature discontinuation caused by progressive disease, toxicity, or death, RDI was calculated up to discontinuation or death. Although not specifically addressed in the remaining studies, RDI was calculated as the ratio of 2 timedependent dose intensities, meaning that premature discontinuation would not result in RDI reduction.…”

Section: Derivation Of Rdimentioning

confidence: 99%

“…19 In only 2 studies was RDI systematically analyzed as a semicontinuous variable in 5% or 10% intervals from 50% to 90%. Yamamoto et al 18 selected a 70% cutoff for all subsequent analyses, as this cutoff corresponded to the most significant impact on event-free survival, whereas, in Hirakawa et al, 11 although significant OS differences were observed using a cutoff of 80%, the researchers elected to use a 70% cutoff, as this approximated the most commonly observed RDI when R-CHOP was dose reduced due to toxicity or patient-related factors. The remaining 6 studies either did not give any justification for the chosen cutoff or referred to precedent.…”

Section: Impact Of DI On Survival Outcomes: All Agesmentioning

confidence: 99%

Impact of R-CHOP dose intensity on survival outcomes in diffuse large B-cell lymphoma: a systematic review

Bataillard

Cheah

Maurer³

et al. 2021

Blood Advances

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The dilemma of whether to treat elderly patients with diffuse large B-cell lymphoma (DLBCL) with a full or reduced dose intensity (DI) of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone+rituximab) is often faced by clinicians. We conducted a systematic review assessing the impact of R-CHOP DI on DLBCL survival outcomes, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (PRISMA-P) guidelines. We searched MEDLINE, EMBASE, and Cochrane CENTRAL for studies with ≥100 patients treated with R-CHOP/R-CHOP–like therapies published from January 2002 through November 2020. Studies were included if they reported the impact of R-CHOP DI on survival outcomes. We screened records, extracted data, and reviewed all the studies for quality and statistical appraisal. Of 380 screened records, 13 studies including 5188 patients were reviewed. DI was often calculated as the ratio of the cumulative delivered dose of prespecified drug(s) to the cumulative planned dose multiplied by a time-correction factor. Lower DI (intended or relative) was associated with inferior survival in 7 of 9 studies reporting crude survival analyses. Multivariable analysis using DI as a covariate was performed in 10 studies. Six showed an association (P < .05) with adjustment for other covariates, and 4 did not. Most studies and those larger studies of higher quality showed poorer outcomes associated with reduced DI. In subgroups aged ≥80 years, survival was not consistently affected by reduced DI. DI-specific randomized trials are warranted, but these data support full-dose R-CHOP in elderly and fit patients aged <80 years with DLBCL, but not in those aged ≥80 years, where dose-reduced R-CHOP does not appear to compromise survival.

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Impact of comorbidity and relative dose intensity on outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP

Cited by 10 publications

References 22 publications

Prophylaxis and treatment strategies for optimizing chemotherapy relative dose intensity

Prophylaxis and treatment strategies for optimizing chemotherapy relative dose intensity

Clinical Outcomes, Treatment Toxicity, and Health Care Utilization in Older Adults with Aggressive Non-Hodgkin Lymphoma

Impact of R-CHOP dose intensity on survival outcomes in diffuse large B-cell lymphoma: a systematic review

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