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The effectiveness of rituximab and HIV on the survival of Ontario patients with diffuse large B-cell lymphoma.

ABSTRACT: INTRODUCTION:For patients with diffuse large B-cell lymphoma (DLBCL), standard-care is rituximab administered with CHOP or CHOP-like chemotherapy (R-CHOP). However, the effectiveness and safety of R-CHOP among DLBCL patients with human immunodeficiency virus (HIV) infection is less clear, as HIV+ patients were omitted from most clinical trials and population-level data from unselected patients are limited. R-CHOP was funded for HIV-associated DLBCL patients with CD4 >50/mm3 in Ontario in February 2015. METHODS:Patients with a new diagnosis of DLBCL were identified from the Ontario Cancer Registry between April 2010 and March 2018. HIV diagnosis and chemotherapy regimen were ascertained using administrative databases at Ontario Health. The effect of rituximab and HIV on overall survival was assessed in the HIV+ subgroup (R-CHOP vs CHOP) and in the R-CHOP subgroup (HIV+ vs HIV-). RESULTS:Among HIV+ patients, receipt of R-CHOP was associated with a fivefold improvement in overall survival (hazard ratio [HR] 0.29 (0.13-0.66) compared with CHOP), after adjustment. Among patients who received R-CHOP (n = 6106), older age, male sex, lower neighborhood income, and higher comorbidity were associated with worse overall survival, after adjustment (P < .001 for all), but HIV positivity was not prognostic (HR 1.12 (0.60-2.10)). Within 1-year after diagnosis, HIV+ patients receiving R-CHOP had a similar proportion of patients who visited the emergency department (67% vs 66% P = .43) or admitted to hospital (58% vs 52%, P = .43) and as HIV- patients receiving R-CHOP. CONCLUSION:HIV status did not affect prognosis for patients with DLBCL receiving R-CHOP in an unselected general population when rituximab was used according to funding criteria. R-CHOP was safe and effective for DLBCL treatment, regardless of HIV status.

SUBMITTER: Habbous S

PROVIDER: S-EPMC7541135 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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The effectiveness of rituximab and HIV on the survival of Ontario patients with diffuse large B-cell lymphoma.

Habbous Steven S Guo Helen H Beca Jaclyn J Dai Wei Fang WF Isaranuwatchai Wanrudee W Cheung Matthew M Chan Kelvin K W KKW

Cancer medicine 20200813 19

<h4>Introduction</h4>For patients with diffuse large B-cell lymphoma (DLBCL), standard-care is rituximab administered with CHOP or CHOP-like chemotherapy (R-CHOP). However, the effectiveness and safety of R-CHOP among DLBCL patients with human immunodeficiency virus (HIV) infection is less clear, as HIV+ patients were omitted from most clinical trials and population-level data from unselected patients are limited. R-CHOP was funded for HIV-associated DLBCL patients with CD4 >50/mm<sup>3</sup> in ...[more]

PMID: 32794362

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Project description:BackgroundCurrent treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice.MethodsWe performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG).ResultsRituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ? 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age.ConclusionsOur results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug.

Project description:BackgroundPopulation-based studies previously showed an improvement in overall survival (OS) for patients with diffuse large B-cell lymphoma (DLBCL) who received chemoimmunotherapy with rituximab. However, there is limited data (especially at the population level) that show a similar trend in OS improvement, in the most recent time period. We hypothesized that survival for DLBCL patients diagnosed in the United States has continued to improve in recent years and intended to measure outcome improvements.MethodsUsing the SEER-18 registries, we compared the incidence and relative survival rates (RSRs) of DLBCL patients between 2002-2007 and 2008-2013 (availability of novel agents, broader use of autologous hematopoietic cell transplantation and improvement in supportive care). Multivariable Cox regression models were used to assess associations between the year of diagnosis and OS while controlling for age, gender, stage, and ethnicity.ResultsThere were a total of 53 439 patients with DLBCL who were diagnosed between 2002 and 2013. Of these, 25 810 were diagnosed during time period-1 and 27 629 diagnosed during time period-2. There was a slight decline in incidence of DLBCL (time period-1 vs time period-2), 7.75 (95% CI = 7.66-7.84) vs 7.43 (95% CI = 7.34-7.52) cases per 100 000 persons, respectively (P < .0001). Overall, there was a modest improvement in DLBCL RSRs, with 5-year RSR improving from 61% (time period-1) to 64% (time period-2) and the improvement was noted across all subsets of patients. On multivariable analysis, patients diagnosed in time period-2 had lower mortality relative to time period-1 (HR = 0.87, 95% CI = 0.85-0.89).ConclusionsOur study shows an improvement in the outcomes of DLBCL patients beyond the introduction of rituximab, although the magnitude of improvement is small. It will be interesting to see the impact of chimeric antigen receptor-T cell therapy translating to population-level survival in the next 5 years.

Project description:PurposeThe addition of rituximab to standard chemotherapy has significantly improved survival in patients with lymphoma. Recently, maintenance therapy with rituximab has been shown to prevent relapse and provide survival benefits for patients with follicular or mantle cell lymphoma. However, the effects of rituximab in patients with diffuse large B-cell lymphoma (DLBCL) remain unclear. Two new studies involving rituximab in the treatment of DLBCL were performed this past year. We performed a meta analysis to evaluate the effects of rituximab maintenance treatment of patients with DLBCL.MethodsSeveral databases (PubMed, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) databases were reviewed for relevant randomized controlled trials published prior to May, 2016. Two reviewers assessed the quality of the included studies and extracted data independently. The hazard ratios (HRs) for time-to-event data and relative risks (RRs) for the other data were pooled and estimated.ResultsTotally 5 studies including 1740 patients were eligible for the meta-analysis. Compared to the observation group, patients who received rituximab maintenance therapy had significantly improved event-free survival (EFS) (HR = 0.80, 95% CI: 0.65-0.98) and progression-free survival (PFS) (HR = 0.72, 95% CI: 0.54-0.94). However, there was no statistically significant difference in overall survival (OS) (HR = 0.66, 95% CI: 0.27-1.29). A subgroup analysis suggested that male patients may benefit from rituximab maintenance therapy with a better EFS (HR = 0.53, 95% CI: 0.34-0.82-), while this advantage was not observed in female patients (HR = 0.99, 95% CI: 0.64-1.52).ConclusionsRituximab maintenance may provide survival benefits beyond that afforded by first- and second-line chemotherapy alone, especially in male patients. However, maintenance rituximab treatment may cause more adverse events. It is recommended that both survival benefits and adverse events should be taken into consideration when making treatment decisions.

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The effectiveness of rituximab and HIV on the survival of Ontario patients with diffuse large B-cell lymphoma.

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The effectiveness of rituximab and HIV on the survival of Ontario patients with diffuse large B-cell lymphoma.

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