A new prognostic score for elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: the prognostic role of blood monocyte and lymphocyte counts is absent.

BACKGROUND: Absolute lymphocyte count (ALC) and absolute monocyte count (AMC) have been documented as independent predictors of survival in patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Analysis of the prognostic impact of ALC and AMC in the context of International Prognostic Index (IPI) and other significant variables in elderly population treated in the R-CHOP regime has not been carried out yet. METHODOLOGY/PRINCIPAL FINDINGS: In this retrospective study, a cohort of 443 newly diagnosed DLBCL patients with age ≥ 60 was analyzed. All patients were treated with the R-CHOP therapy. An extensive statistical analysis was performed to identify risk factors of 3-year overall survival (OS). In multivariate analysis, only three predictors proved significant: Eastern Cooperative Oncology Group performance status (ECOG), age and bulky disease presence. These predictors were dichotomized (ECOG ≥ 1, age ≥ 70, bulk ≥ 7.5) to create a novel four-level score. This score predicted 3-year OS of 94.0%, 77.4%, 62.7% and 35.4% in the low-, low-intermediate, high-intermediate and high-risk groups, respectively (P<0.001). Further, a three-level score was tested which stratifies the population better (3-year OS: 91.9%, 67.2%, 36.2% in the low, intermediate and high-risk groups, respectively) but is more difficult to interpret. Both the 3- and 4-level scores were compared to standard scoring systems and, in our population, were shown to be superior in terms of patients risk stratification with respect to 3-year OS prediction. The results were successfully validated on an independent cohort of 162 patients of similar group characteristics. CONCLUSIONS: The prognostic role of baseline ALC, AMC or their ratio (LMR) was not confirmed in the multivariate context in elderly population with DLBCL treated with R-CHOP. The newly proposed age-specific index stratifies the elderly population into risk groups more precisely than the conventional IPI and its existing variants

Multivariate model results.

<p><i>Results of the final multivariate 3-year overall survival (OS) model: Hazard rate (HR) with its 95% confidence interval (CI) and P-value based on the Cox regression model.</i></p

Overall survival (OS) and Progression-free survival (PFS) curves for the entire cohort.

<p>Complete follow-up.</p

Summary of all the prognostic factors.

<p><i>Results of the univariate 3-year overall survival (OS) analyses: hazard rate (HR) with its 95% confidence interval (CI) and P-value based on the Cox regression model. Descriptive statistics of all the prognostic factors.</i></p

Rituximab maintenance significantly reduces early follicular lymphoma progressions in patients treated with frontline R‐CHOP

Abstract Twenty percent of patients with high‐tumor‐burden (HTB) follicular lymphoma (FL) develop progression/relapse of disease (POD) within 24 months of frontline immunochemotherapy. Unfortunately, about 50% of these patients die within 5 years since POD event. Rituximab maintenance was proven to reduce relapse rate in responding FL, but its role on preventing POD was not defined. We analyzed 1360 HTB‐FL patients from the Czech Lymphoma Study Group registry treated with frontline rituximab‐containing regimen. Of those, 950 cases received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) and achieved complete or partial remission: 712 patients received rituximab maintenance (MAINT) and 238 were a historical observational cohort (OBS). We have proposed a modified POD24 (mPOD24) endpoint for the chemosensitive patients calculated from the end‐of‐induction (EOI). Survival rates since EOI were as follows: 5‐year overall survival (OS) 86.2% versus 94.5% in the OBS and MAINT groups, respectively (P < .001) and 5‐year progression‐free survival 58.5% (OBS) and 75.4% (MAINT) (P < .001). The Cox proportional hazards model showed a decrease in mPOD24 incidence in the MAINT group with the overall hazard rate reduced by 56% (hazard ratio = 0.44; P < .001). The cumulative incidence of mPOD24 was reduced from 24.1% in OBS to 10.1% in MAINT (P < .001). Comparison of non‐mPOD24 cases showed OS similar to that in the general population. Rituximab maintenance given after R‐CHOP resulted in a 2.4‐fold reduction in mPOD24 incidence. Once the non‐POD24 status is achieved, FL does not shorten the patients’ life expectancy

3-year overall survival (OS) curves for the entire cohort stratified by the ECOG score.

<p>The hazard rates of groups 1, 2, 3, 4 relative to group ECOG = 0 are 2.85, 3.89, 3.82, 24.58, respectively. Notice the clear separation of the group ECOG = 4 from the rest of the population. However, group ECOG = 4 contains only 8 patients. Optimal stratification of the population into two groups thus separates group ECOG = 0 (109 patients) from the rest of the population (334 patients).</p

Summary of the validation of the ABE scoring systems.

<p><i>Results of the univariate 3-year overall survival analysis in the training and the validation data sets: hazard rate (HR) with its 95% CI and P-value based on the Cox regression model. Reference group in all regression models is the lowest risk group. The measure of concordance compares the model discrimination.</i></p

Comparison of the novel scores with the existing ones.

<p><i>Results from comparison of newly constructed scores (ABE4-Score and ABE3-Score) with several existing scoring systems. The measure of concordance compares the model discrimination, the Akaike Information Criterion (AIC) compares the model fit.</i></p

Overall survival (OS) curves for the entire cohort stratified by the 4-level scoring systems: the proposed novel ABE4-Score, and the classical IPI, AA-IPI, and E-IPI scores.

<p>Overall survival (OS) curves for the entire cohort stratified by the 4-level scoring systems: the proposed novel ABE4-Score, and the classical IPI, AA-IPI, and E-IPI scores.</p