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

Abstract

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.

The Prognostic Impact of Comorbidities in Patients with De-Novo Diffuse Large B-Cell Lymphoma Treated with R-CHOP Immunochemotherapy in Curative Intent

“…This proportion is within the range of 5.8-26% reported in retrospective series in the literature [19][20][21]31]. In a study focusing on patients with DLBCL at advanced age (≥75 years) a CCI ≥ 2 was detected in 34.9% [22], which is slightly above the prevalence of 26.7% in our subgroup [22]. This difference might be explained by the selection of patients in our cohort, who were considered to be fit to tolerate R-CHOP therapy based on evaluation by the treating physicians.…”

“…The Charlson Comorbidity Index (CCI) was originally developed to elaborate the prognostic significance of comorbidities irrespectively of the underlying disease [17]. This score has also been used to estimate the comorbidity burden in cancer patients [18], including DLBCL [19][20][21][22]. The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) was developed to evaluate the feasibility and the risk of patients undergoing intensive therapy and hematopoietic stem cell transplantation (HSCT) [23][24][25][26].…”

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

“…Reduced intensity regimens, such as R-mini-CHOP, nonanthracycline regimens including rituximab monotherapy and rituximab- cyclophosphamide-vincristine-prednisone, or those substituting doxorubicin with gemcitabine or etoposide may be considered in these patients. 1,2,8 A number of clinical trials targeting elderly patients age ≥ 80 years or patients of advanced age (≥ 60 years) who have comorbidities and are not candidates for standard R-CHOP are currently underway. Novel regimens under investigation include lenalidomide and rituximab (NCT02955823), R-mini-cyclophosphamide, doxorubicin, and prednisone (CHP) with polatuzumab vedotin (NCT04332822), mosunetuzumab monotherapy (NCT03677154), and R2-mini-CHOP (NCT02128061).…”

“…++ + + + + + ++++ + + + + + + ++ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + ++ + + + + + + + + + + + + + + + ++ + + ++ + ++ + + ++ + + + + + + + + ++ + ++ ++ + + + ++ + + + + + +++ +++ ++ Kaplan-Meier analysis of OS according to Tolerability of R-CHOP in Aggressive Lymphoma risk group in (A) the GOYA holdout data set and (B) the MAIN external validation data set. OS, overall survival.Predicting Immunochemotherapy Tolerability in DLBCL cyclophosphamide-vincristine-prednisone, or those substituting doxorubicin with gemcitabine or etoposide may be considered in these patients 1,2,8. A number of clinical trials targeting elderly patients age ≥ 80 years or patients of advanced age (≥ 60 years) who have comorbidities and are not candidates for standard R-CHOP are currently underway.…”

Economic Burden in Treated Japanese Patients with Relapsed/Refractory Large B-Cell Lymphoma

“…Due to the relatively older patient population of our study (median ≥70 years in both 2L and 3L cohorts), who are likely ineligible for SCT, the heterogeneous salvage regimens reflect the nature of the population and the small number of SCT procedures observed in this study (14 and 20% for 2L and 3L cohorts, respectively). Another study also provided a different perspective on adopting alternative therapies to R-CHOP for elderly patients with DLBCL from 1L treatment, although it was acknowledged that there is no single standard 2L therapy for SCT-ineligible r/r DLBCL patients [ 27 ]. The trend of more elderly patients receiving GDP-based and DeVIC-based therapies as both 2L and 3L regimens, as identified in this study, may warrant further investigation to understand whether these therapies result in a superior prognosis for elderly patients, especially those who are ineligible for allo-SCT.…”