R-CHOP Group Research Articles

Long-Term Safety and Effectiveness of Rituximab Biosimilar RTXM83: A Retrospective Extension Study in Brazilian Patients with Diffuse Large B-Cell Lymphoma.

RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical,and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. The median follow-up period was 77.0months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. ClinicalTrials.gov Identifier:NCT04928573. June 16, 2021, "retrospectively registered".

The Reduction of CD4+ T Lymphocytes after the Treatment of Follicular Lymphoma with the Bendamustine Containing Regimen May Predict the Occurrence of Infection and Efficacy

To investigate the effectiveness, safety, and related prognostic factors of the treatment of follicular lymphoma (FL) with a regimen containing Bendamustine. The clinical data of 129 FL patients who were treated with Bendamustine containing regimen were collected from January 1,2020 to October 30,2022 in the Hematology Department of Lianyungang Second People's Hospital and Jiangsu Provincial People's Hospital. The patients were divided into three groups: Bendamustine plus Rituximab (BR), Bendamustine plus Obinutuzumab (GB), Rituximab + Cyclophosphamide + Epirubicin / Doxorubicin + Vindesine + Prednisone (R-CHOP). The efficacy, safety and related prognostic factors of the treatment of FL with a regimen based on Bendamustine were retrospectively analyzed. The ORR was 98% for the BR group, 94% for the GB group, and 72.3% for the R-CHOP group, while the CR rate was 61.2%,70% and 40.4%, respectively. The ORR and CR rates of the R-CHOP group were statistically different from those of the BR group and GB group (P < 0.05). The 3-year PFS rate of the BR group, GB group, and R-CHOP group was 89.6%, 90.9%, 48.9%, respectively. There was a statistically significant difference in 3-year PFS between the R-CHOP group, BR group, and GB group (P < 0.05), while there was no statistically significant difference in 3-year OS（P ＞0.05）. Hematological adverse reactions were mainly bone marrow suppression. Lymphocytes and CD4+T lymphocytes decreased to the lowest level about 6 months after treatment, and the incidence of lymphopenia in BR group and GB group was higher than that in R-CHOP group, with a statistical difference (P < 0.05). The higher incidence of non-Hematological adverse reactions were pulmonary infection, EB virus infection, hepatitis B virus reactivation, and gastrointestinal reactions without statistical difference in 3 groups (P >0.05), and were all controllable. The Receiver operating characteristic of CD4+T lymphocyte count showed that AUC of BR group was 0.802, and the critical value was 258/uL; AUC of GB group was 0.754 with a critical value of 322/uL. The treatment of FL with the Bendamustine containing regimen has good efficacy and controllable adverse reactions, but lymphocytopenia was significant after treatment, and the curative efficacy in combination with various CD20 monoclonal antibodies was different. The lowest CD4+T lymphocyte count can be used as a predictive factor for the occurrence of infection and efficacy of the Bendamustine containing regimen for FL.

Long-term outcomes with HLX01 (HanliKang®), a rituximab biosimilar, in previously untreated patients with diffuse large B-cell lymphoma: 5-year follow-up results of the phase 3 HLX01-NHL03 study

HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2–76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9–87.5%) and 75.4% (95% CI: 68.9–82.6%)( HR: 0.75, 95% CI 0.47–1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4–84.6%) and 73.0% (95% CI: 66.3–80.3%) (HR: 0.84, 95% CI 0.54–1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.

Hepatitis B surface antigen positivity is associated with poor short- and long-term outcomes in patients with diffuse large B-cell lymphoma who received CHOP or R-CHOP.

The development of diffuse large B-cell lymphoma (DLBCL) is closely related to the host infection status. China is a highly endemic area for hepatitis B virus (HBV) infection. It is not clear whether HBV infection has a consistent effect on the prognostic implications of patients with DLBCL in different treatment settings. We conducted a cohort study of 692 patients with DLBCL receiving three or more cycles of treatment with a CHOP or R-CHOP regimen from the First Hospital of Jilin University between July 2011 and July 2022. The patients were divided into two groups based on their hepatitis B surface antigen (HBsAg) status: HBsAg-positive (n = 84, 12.1%) and HBsAg-negative (n = 608, 87.9%) groups. Tumor specimens from 180 patients with primary DLBCL were collected for next-generation sequencing (NGS). The HBsAg-positive group had more frequent abnormal liver function (P= 0.003), hypoalbuminemia (P < 0.001), incidence of > 2 extranodal organs (P= 0.011), and spleen involvement (P < 0.001) than the HBsAg-negative group. HBsAg-positive patients had lower complete response (CR) and overall response rates (ORR) rates (all the p values < 0.05), in either the CHOP group or R-CHOP group. Among patients receiving R-CHOP, the rates of disease progression within 12 and 24 months were higher in the HBsAg-positive group than in the HBsAg-negative group (P=0.018, P=0.029). However, no significant difference in disease progression was observed between HBsAg-positive and HBsAg-negative patients in the CHOP group(P > 0.05). HBsAg positivity (OS: HR [95% CI] = 2.511 [1.214-5.192], P = 0.013) was only associated with poorer OS in the CHOP group. Whereas in the R-CHOP group, HBsAg positivity was associated with both poorer OS and PFS (OS: HR [95% CI] = 1.672 [1.050-2.665], P = 0.030; PFS: HR [95% CI] = 1.536 [1.013-2.331], P = 0.043). Additionally, HBsAg-positive patients with DLBCL also had a higher prevalence of mutations in MYC, ATM, PTPN6, and epigenetically regulated genes. These findings suggest that HBsAg-positive DLBCL patients may represent a distinct subgroup with a poorer prognosis. The standard therapies may be insufficient and new therapeutic strategies should be developed based on a better understanding of the underlying mechanisms of chemoresistance.

Results of R-CHOP and R-CHOP + interleukin-2 regimens in first-line therapy in patients with diffuse B-cell lymphoma

The study was made to evaluate the effect of interleukin-2 (IL-2) as part of the R-CHOP regimen on the rate of a complete metabolic response (CMR) using the data of interim positron emission tomography (PET/CT) and progression-free survival compared to the standard regimen in patients with diffuse B-cell lymphoma (DCLC). The data of 152 patients with biopsy-proven DCLC who were treated in the period 2015–2020 were included. Among them, 59 patients were included in the prospective group (R-CHOP + IL-2 in a total course dose of 5,000,000 IU). The control group consisting of 93 patients received standard R-CHOP therapy. PET/CT was performed after 4 courses of therapy, metabolic response was assessed using the Deauville scale, and Deauville 1-2 was classified as CMR. The rate of CMR in the R-CHOP+IL-2 group was 67.8 %, while in the control group it was 50.5 % (pχ² = 0.044). The 5-year progression-free survival (PFS) in the R-CHOP+IL-2 and R-CHOP groups was 80.7 and 64.5 %, respectively (p = 0.04). In the favorable and intermediate prognosis groups (IPI 0–3), PFS was not statistically significantly different depending on treatment. At high risk (IPI 4–5), the 5-year PFS in the R-CHOP + IL-2 and R-CHOP groups was 71.4 and 25.0 %, respectively (p = 0.02). Including IL-2 in the R-CHOP regimen in the first-line treatment of patients with DCLC increases the incidence of CMR according to 18-FDG PET/CT after 4 courses of chemoimmunotherapy and PFS in the high-risk group.

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution.

To compare the efficacy and safety of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL) at a single institution. This retrospective study included 115 newly diagnosed patients with WR-DLBCL, of whom 68 patients received R-CHOP, and 47 patients received DA-EPOCH-R as their first-line treatment. The baseline features of the two groups were well balanced using a 1:1 propensity score matching method, and a total of 84 cases were obtained, including respective 42 cases in the R-CHOP and DA-EPOCH-R groups, for further survival and prognosis analysis. The primary objectives included progression-free survival (PFS) and overall survival (OS). During a median follow-up of 45 months, there were nine (21.4%) deaths in the R-CHOP group and two (4.8%) in the DA-EPOCH-R group. Kaplan-Meier analysis showed statistically significant improvements in PFS and OS in patients with DA-EPOCH-R compared with those treated with R-CHOP (log-rank test, P = 0.025 and P = 0.035, respectively). The 2-year PFS and OS rates in the DA-EPOCH-R group were 90.1% (95% confidence interval [CI]: 81.4-99.8%) and 95.2% (95% CI: 89.0-100.0%), respectively, and 80.5% (95% CI: 69.3-93.6%) and 90.5% (95% CI: 52.8-99.8%) in the R-CHOP group. Patients without B symptoms and elevated lactate dehydrogenase levels had a higher PFS in the DA-EPOCH-R group, with P values of 0.038 (hazard ratio [HR]: 0.11; 95% CI: 0.01-0.88) and 0.042 (HR: 0.19; 95% CI: 0.04-0.94), respectively. There were no statistically significant differences in clinical responses and treatment-related toxicities between the two groups. Compared with patients received R-CHOP, those treated by DA-EPOCH-R had superior PFS, OS, and controlled toxicity in patients with WR-DLBCL.

Clinical Characteristics and Prognosis of Patients with Primary Testicular Diffuse Large B-Cell Lymphoma

To analyze the clinical manifestations, therapeutic response and prognosis of patients with primary testicular diffuse large B-cell lymphoma (PT-DLBCL). Thirty-eight patients with PT-DLBCL were enrolled, who hospitalized from January 2010 to April 2021, and their clinical characteristics, treatment regimen and efficacy were collected and analyzed retrospectively. The median age of the patients was 56 years old (ranged from 38 to 79 years). There were 4 cases (10.5%) with bilateral lesions, 13 cases (34.2%) with left lesions, and 21 cases (55.3%) right lesions. There were 2 cases(5.3%) with B symptoms, 6 cases (15.8%) of germinal center B-cell-like(GCB) subtype and 32 cases(84.2%) of non-GCB subtype. Efficacy was evaluated in 36 cases, including 10 cases with CHOP regimen, 21 cases with R-CHOP regimen (7 cases were treated with rituximab combined with high-dose methotrexate injection chemotherapy at intervals of R-CHOP regimen), and 5 cases with other regimens. In 36 patients, the efficacy evaluation of initial chemotherapy showed that the overall response rate (ORR) was 86.1%, 29 cases (80.6%) reached complete response (CR), and 2 cases (5.5%) reached partial response (PR). The R-CHOP group was superior to CHOP group in ORR (95.2% vs 60.0%, P=0.027) and CR (90.4% vs 50.0%, P=0.022). Of the 36 patients, 7 cases had central nervous system(CNS) recurrence and 4 cases had contralateral testicular recurrence. Compared with the CHOP group, the CNS recurrence rate in the R-CHOP group was significantly lower (4.8% vs 50.0%, P=0.007), and the testicular recurrence rate in the R-CHOP group was also lower than the CHOP group, but the difference was not statistically significant (4.8% vs 30.0%, P=0.087). The median follow-up time was 27(3-135) months, and the 5-year PFS and OS were 71% and 74%, respectively. Kaplan-Meier univariate analysis showed that the R-CHOP regimen significantly improved the patients' PFS (P=0.024) and OS (P=0.025) compared with the CHOP regimen. PT-DLBCL is mainly treated with comprehensive treatment. Compared with CHOP regimen, R-CHOP regimen can improve the CR rate and ORR, reduce CNS recurrence and contralateral testicular recurrence, and improve the patients' survival. Patients may benefit from high-dose methotrexate combined with rituximab interlaced with R-CHOP regimen.

A Propensity Score-Adjusted Comparison of Lenalidomide + R-CHOP Versus R-CHOP for MYC-Rearranged DLBCL Patients

Introduction Patients with MYC rearranged (MYC-R) diffuse large B-cell lymphoma (DLBCL) generally have a poor prognosis following standard treatment with R-CHOP. Previously, we demonstrated in a single-arm phase II trial (HOVON-130) that addition of lenalidomide to R-CHOP (R2CHOP) is well-tolerated and yields similar complete metabolic remission (CMR) rates and survival as more intensive chemotherapy regimens such as DA-EPOCH-R [Chamuleau, Haematologica 2020]. In parallel with this single-arm interventional trial, a prospective observational screening cohort (HOVON-900) was open in which we identified all newly diagnosed DLBCL patients treated with R-CHOP in the Netherlands, including MYC-R patients who were not included in the interventional trial due to logistic reasons. These two cohorts enable to evaluate the added value of lenalidomide to R-CHOP in first-line treatment of newly diagnosed MYC-R DLBCL patients. Methods In the single-arm, phase-II HOVON-130 trial, MYC-R DLBCL patients ≥ 18 years were treated with R-CHOP21 plus lenalidomide 15 mg day 1-15 for 6 cycles [Chamuleau, Haematologica 2020]. Additional inclusion criteria were Ann-Arbor stage II-IV, WHO performance status 0-3, ≥ one lesion of ≥ 1.5 cm on contrast-enhanced CT scan and ≥ one FDG-positive lesion on PET-CT scan. In the observational screening study HOVON-900, MYC, BCL2 and BCL6 fluorescent in situ hybridization (FISH) diagnostics were advocated as part of routine procedures and reviewed by the HOVON Pathology Facility. As a control group, we selected MYC-R patients from this observational cohort who met the inclusion criteria for the interventional trial but were not included, and who were treated with standard R-CHOP. Clinical information at presentation and treatment and outcome data were retrieved from the Netherlands Cancer Registry. We explored three statistical methods that account for baseline imbalances. First, we used multivariable regression, with baseline variables as covariates in the model. Second, we performed one-to-one matching on the IPI risk (low, intermediate, or high). Third, we performed inverse probability of treatment weighting (IPTW) using a propensity score. We calculated a propensity score for being included in the HOVON-130 trial based on the separate components of the IPI score (i.e., age, Ann Arbor stage, WHO performance score, extra-nodal localizations, serum LDH level), sex and rearrangement status. To allow for some degree of misspecification of the model for the propensity score, we used a doubly-robust estimator. Subgroup analyses were performed in single hit (SH: only MYC rearrangement), versus double hit and triple hit (DH/TH: MYC rearrangement with BCL2 and/or BCL6 rearrangement). Results Patients from the interventional trial treated with R2CHOP (n=77) were younger than patients in the control cohort (n=56) treated with R-CHOP (median age 63 versus 70 years, p=0.018) and they were more likely to have a lower WHO performance score (p=0.013). Ann Arbor stage, LDH level, number of extranodal localizations and median days before treatment (15 and 19 in the R-CHOP and R2CHOP group, respectively) did not significantly differ between the groups. Complete remission rates were 69.8% and 80.5% in the R-CHOP and R2CHOP group, respectively (p=0.209). Multivariable analysis, 1:1 matching and weighting using the propensity score consistently showed improved outcome after R2CHOP with HRs of 0.53, 0.53, and 0.59 (Figure 1A), respectively, for OS, and 0.59, 0.53, and 0.60 for PFS (Figure 1B). In the subgroups determined by rearrangement status, we performed unadjusted OS and PFS analysis only, because we were not able to adjust for baseline imbalances because of the low number of events within the subgroups. Both SH patients and DH/TH patients tended to have a longer OS when treated with R2CHOP with HRs of 0.34 and 0.57, respectively. Similarly, for PFS the HRs were 0.66 in the SH subgroup and 0.48 in the DH/TH subgroup. Conclusion In conclusion, this propensity score-adjusted comparison study supports the addition of lenalidomide to R-CHOP as a valuable treatment option for MYC-R DLBCL patients. R2CHOP can be administered on a full outpatient basis, with minimal hospitalization visits. Future studies will explore whether adding next-generation cereblon targeting antigens to R-CHOP can improve the observed effects. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ABCL-322 Retrospective Analysis of Real-World Outcomes in Older Adult Patients With Diffuse Large B-Cell Lymphoma

Treatment of older adult patients with diffuse large B-cell lymphoma (DLBCL) seeks to achieve disease remission while minimizing treatment-related toxicities. The use of anthracycline in older adults is associated with increased risk of cardiotoxicity and myelosuppression. Non-anthracycline-based regimens have commonly been used in patients ineligible or at risk of severe toxicities to anthracyclines. To analyze the treatment outcomes of patients with DLBCL aged ≥60 years and compare R-CHOP and R-CEOP regimens. Retrospective study, median follow-up: 22.71 months (IQR 8.55-39.24 months). Single institution, tertiary care cancer center. Those aged ≥60 years and newly diagnosed with DLBCL between January 2014 and December 2018 were included. Of a total of 218 patients, 71 patients received the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) and 137 received R-CE(etoposide)OP chemotherapy. The decision to substitute etoposide for doxorubicin was based on physician's discretion depending on the patient's performance status, cardiac comorbidities, frailty, and available resources for supportive care. Two-year progression-free survival (PFS), 2-year overall survival (OS), Grade III/IV toxicities. The 2-year PFS rate in the R-CHOP group was higher than that in the R-CEOP group (79.1% vs. 49.6%, P-value<0.001); this superiority of R-CHOP was seen in both early and advanced disease. The 2-year OS rate in the overall cohort was significantly higher in the R-CHOP group (86.2% vs. 70.6%, P-value=0.016), and the age group of 60-65 years showed significantly better outcomes with the anthracycline-based regimen. The incidence of febrile neutropenia and grade III/IV hematological toxicities was significantly higher in the R-CHOP group in the age group of 60-65 years. Multivariate analysis showed that ECOG-PS, NCCN-IPI, and chemotherapy regimen were significant factors for 2-year PFS, and NCCN-IPI and chemotherapy regimen were significant factors for 2-year OS. An anthracycline-based regimen should be used in fit older adult patients without absolute cardiac contraindications with careful monitoring for toxicities and access to supportive care. Geriatric assessment tools should be used for better objective assessment of fitness to deliver optimal therapy and lessen the risks of toxicities.

A RETROSPECTIVE STUDY OF DIFFUSE LARGE B CELL LYMPHOMA (DLBCL) FROM A TERTIARY CANCER HOSPITAL IN SOUTH INDIA

Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid neoplasm in adults. It accounts for 30% of Non-Hodgkin's lymphomas (NHLs) diagnosed annually [1].The present study aims to evaluate the outcome of the patients who received CHOP(Cyclophosphamide, Adriamycin, Vincristine, Prednisolone) and R(Rituximab)-CHOP treatment and also correlates the different patient characteristics. This was a retrospective analysis carried out on 65 pat Materials &amp; Methods: ients, diagnosed with DLBCL treated from December 2013 to July 2019. A total of 65 cases were studied and their different Results: clinical characteristics are presented in (Table 1). The median age of the study population was 44 years (19–75 years). The male-to-female ratio was 1:0.5. 3year OS (overall survival) was 32% and 43% in CHOP and R-CHOP group and statistically, a signicant difference was seen in both the groups p&lt;0.001. Rituximab based Conclusion: chemoimmunotherapy showed better response rate irrespective of cell of origin.

Patient characteristics and outcome of CD20-positive HIV-associated lymphoma: a single-center KwaZulu-Natal, South African hospital 12-year retrospective review

BackgroundDue to the high prevalence of HIV, HIV-associated lymphoma (HAL) is a common malignancy in South Africa. However, there is a paucity of literature on HAL from this region. The objective of this study was to profile the clinical characteristics and outcome of CD20-positive HAL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), with or without rituximab (R), from a single center in KwaZulu -Natal, South Africa.MethodsRetrospective chart review of adult patients treated from 2006 to 2018 for HIV-associated CD20-positive lymphoma. The clinical characteristics, complete response (CR), and 2-year overall survival (OS) are described.ResultsThe analysis included 102 patients, 54% females, median age of 39 years, and median CD4 cell count of 196 cells/μL. Bone marrow involvement was noted in 5%. Eighty-six percent of the cohort received concomitant antiretroviral therapy and chemotherapy, 76% of the CHOP group, and 92% of the R-CHOP group. Overall, a CR was seen in 55% (95% CI 45%; 65%), with a 2-year OS of 59% (95% CI 50%, 69%). A CR was attained in 46% on CHOP and 64% on R-CHOP, with a 2-year disease-free survival (DFS) for CHOP of 42% and 50% for R-CHOP.ConclusionAlthough the clinical characteristics and laboratory findings are similar to other higher-income cohorts, there was a difference in gender and incidence of marrow involvement. The low incidence of marrow involvement has prompted more routine use of immunohistochemistry and flow cytometry in staging marrows of HAL locally. Further randomized studies are required for the establishment of locally validated, cost-effective treatment guidelines.

Comparative analysis of rituximab or obinutuzumab combined with CHOP in first-line treatment of follicular lymphoma.

PurposeRituximab (R) or obinutuzumab (G) combined with CHOP chemotherapy are used in previously untreated follicular lymphoma (FL). The aim is to compare in real life setting the efficacy and safety of these therapeutic strategies and assess the economic impact of introducing G.MethodsThis retrospective study, performed in 3 centers, included data from all patients who received R-CHOP or G-CHOP for previous untreated FL from June 1st, 2016 to December 31st, 2020. Progression-Free Survival (PFS) were estimated according to the Kaplan–Meier method. A budgetary impact model was performed from the French health care system’s perspective.ResultsN = 124 patients were included (58 G-CHOP; 66 R-CHOP). Fifty-one and 57 patients achieved a complete response at the end of induction in the G-CHOP and R-CHOP group, respectively. PFS was not significantly longer in the G-CHOP group (HR 0.28; 95% CI 0.08–0.97; p value = 0.14). Hematological toxicity occurred more frequently with G-CHOP than R-CHOP during induction treatment (n = 58; 100% vs. n = 61; 92%), including higher severe neutropenia (grade ≥ 3) (n = 26; 45% vs. n = 23; 35%). Infusion-related reactions during the first infusion occurred more frequently with G-CHOP (n = 19; 33% vs. n = 16; 24%). The introduction of a completed G treatment (induction and maintenance) results in an additional cumulative cost per patient estimated at more than €30,000.ConclusionSimilar results were found in the GALLIUM subgroup analysis study, suggesting that at this time there is no absolute benefit to administer G-CHOP instead of R-CHOP in all patients with previously untreated FL and may encourage clinical and economic trials including quality of life data.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00432-022-04155-2.

“Diffuse Large B-Cell Lymphoma in the Elderly: Real-World Outcomes From a Developing Country”

BackgroundTreatment of Diffuse Large B-Cell Lymphoma (DLBCL) in the elderly aims to achieve disease remission while minimizing treatment-related toxicities. The use of anthracycline in the elderly is associated with increased risk of cardiotoxicity and myelosuppression. Non-anthracycline-based regimens have commonly been used in patients with cardiac contraindications or anticipated severe toxicities to anthracyclines. MethodsWe retrospectively analyzed the treatment outcomes of patients, aged 60 years and above, newly diagnosed with DLBCL at our center. Of a total of 218 patients, 71 patients received the R-CHOP regimen (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone) and 137 received R-CE (Etoposide) OP chemotherapy. The decision to substitute etoposide for doxorubicin was based on physician's discretion depending on the performance status, cardiac comorbidities and frailty as well as available resources for supportive care. ResultsThe 2-year progression-free survival (PFS) rate in the R-CHOP group was higher than that in the R-CEOP group (79.1% vs 49.6%, P-value < .001) and this superiority of R-CHOP was seen in both early and advanced disease. The incidence of febrile neutropenia and grade III/IV hematological toxicities was significantly higher in the R-CHOP group in the age group of 60 to 65 years’. ECOG PS at presentation, NCCN-IPI and the chemotherapy regimen were found to be significant factors for 2-year PFS rate by multivariate analysis. ConclusionAnthracycline-based regimen should be used in elderly fit patients without absolute cardiac contraindications wherever feasible with adequate access to supportive care.

Rituximab-Based Regimens for Treatment of Primary Gastric Diffuse Large B-Cell Lymphoma

To analyze clinical response of the Rituximab-based chemotherapy and prognostic features in patients with primary gastric diffuse large B-cell lymphoma (PGDLBCL). From June 2008 to December 2020, the data of 53 PGDLBCL patients were analyzed retrospectively. The median age was 46(25-77) years old in 53 patients including 35 males and 18 females. Stomachache is the most common symptom. The diagnosis were confirmed in 47 patients by endoscopic biopsy and 6 patients by surgery. Twenty-six patients had Ⅰ/Ⅱ1 stage (Lugano staging system) disease and 27 cases had II2/IV stage disease. All patients were treated with chemotherapy, including RCHOP (25/53) and R-DA-EPOCH (28/53). Complete remission rate was 79.2%（42/53）. The 3-year and 5-year overall survival (OS) rates were 77.4% and 69.8%. Univariate analysis showed that lactate dehydrogenase(LDH), Lugano stage and lesion size affected OS. Multivariate Cox regression analysis revealed that IPI score and Lugano stage were independent prognosis risk factors affecting OS. The patients in the R-DA-EPOCH group presented better survival outcomes than those in the RCHOP group with late stage (P5-year OS=0.035). Rituximab in combination with chemotherapy is the backbone of therapy for PGDLBCL. IPI score and Lugano stage are independent prognosis risk factors affecting OS of PGDLBCL. R-DA-EPOCH can be superior to R-CHOP as a first-line regimen in PGDLBCL patients with late stage.

Hexokinase II expression as a prognostic marker in diffuse large B-cell lymphoma: pre- and post-rituximab era.

We aimed to assess HKII expression and its prognostic significance in diffuse large B-cell lymphoma (DLBCL) patients. The HKII protein level was determined by immunohistochemistry in 159 newly diagnosed DLBCL patients, and its relationship with overall response rate, progression-free survival (PFS), and overall survival (OS) was analyzed. HKII was expressed in 95 DLBCL patients (59.7%). HKII-positive patients had poorer outcomes than negative patients for 5-y PFS (68% vs. 84%, p = 0.029) and 5-y OS (78% vs. 94%, p = 0.05). When only patients without no bulky disease, B symptoms, or extranodal involvement who had low IPI scores were considered, those with positive HKII had worse 5y-PFS and 5y-OS (p < 0.05). Multivariate analysis indicated that HKII status was an independent prognostic factor of OS. In subgroup analysis, HKII expression was associated with inferior OS in the CHOP group (p = 0.017). In CHOP group patients without bulky disease or extranodal involvement who had low LDH and low IPI scores (p < 0.05), positive HKII was associated with worse PFS and OS. No differences in PFS and OS, or any independent prognostic factors, were found in the RCHOP group. In DLBCL, HKII is valuable as a prognostic biomarker and may be useful as a tool for assessing disease risk.

Toxicities Associated With Dose-Adjusted Epoch-R Compared With R-Chop as Frontline Therapy for Diffuse Large B-Cell Lymphoma: A Study Conducted in a Tertiary Level Hospital of Bangladesh

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). This is a heterogeneous group of hematological malignancy of large B lymphocytes with a diffuse growth pattern. Managing DLBCL is challenging because of the biological and clinical heterogeneity of the disease and toxicities during treatment. Methods: This quasi experimental study was conducted at DMCH Hematology department from January 2018 to June 2019 including nineteen, newly diagnosed diffuse large B cell lymphoma with stage I to IV A/B cases. Protocol was approved by ethical review committee (ERC) of Dhaka Medical College Hospital(DMCH). Patients fulfilling the inclusion criteria were enrolled using convenient purposive sampling and then allotted any one of the two regimen groups. Results: Total nineteen (19) DLBCL cases were enrolled for this study and divided into two groups as arm A treated with RCHOP(10 cases) and arm B treated with RDA- EPOCH (9 cases) . Mean age of all patients was 41 years (range 16 to 60 Y). Among them majority (13/69%) of the patients were below 50 years of age and M: F ratio was 2:1.102 cycles of chemotherapy were administered among 20 patients. In R-CHOP group of patients, Grade 1-2 Anemia was found in 14 cycles (28.0%). In R-DA-EPOCH group Grade 1-2 Anemia was found in 14 cycles (31.1%). Grade 3-4 thrombocytopenia was found in 6 cycles (12%) in R-CHOP group. On the other hand, Grade 3-4 thrombocytopenia was found in 4(8.89%) patients in R-DA-EPOCH group. There were 4 episodes of neutropenic fever (8% of cycles) in R-CHOP group and 3 episodes (6.7% of cycles) in R-DA-EPOCH group. 8 out of 10 patients suffered from grade 1-2 anemia in R-CHOP group and 8 out of 9 patients suffered from grade 1-2 anemia. 2 out of 9 patients suffered from grade 3-4 thrombocytopenia in RDA- EPOCH group. Grade 3-4 hemorrhage occurred in 1(10%) patient in R-CHOP group and 2 (22.2%) patients in R-DA-EPOCH group. Mucocitis (grade 1-2) was found in 5 patients (50%) in R-CHOP group and 8 cycles (88.8%) in R-DA-EPOCH group which was not statistically significant. Diarrhea (grade 1- 2) was found in 2 patients (20%) in R-CHOP group and 5 patients (55.5%) in R-DA-EPOCH group. Neuropathy was found in 3 patients (30%) in R-CHOP group and 1 patient (11.1%) in R-DA-EPOCH group. Febrile neutropenia was found in 4 patients (40%) in R-CHOP group and 3 patients (33.3%) in R-DA-EPOCH group. Conclusion: From the result of this study it can be concluded that, Overall incidence of grade 3-4 anemia, thrombocytopenia and diarrhea was more in R-DA- EPOCH group and neuropathy was more common in R-CHOP group. Bangladesh J Medicine 2022; 33: 161-167

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma

BackgroundDiffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody–drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells.MethodsWe conducted a double-blind, placebo-controlled, international phase 3 trial to evaluate a modified regimen of R-CHOP (pola-R-CHP), in which vincristine was replaced with polatuzumab vedotin, as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk DLBCL. Patients 18 to 80 years of age were randomly assigned in a 1:1 ratio to receive six cycles of either pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival and safety.ResultsOverall, 879 patients underwent randomization: 440 were assigned to the pola-R-CHP group and 439 to the R-CHOP group. After a median follow-up of 28.2 months, the percentage of patients surviving without progression was significantly higher in the pola-R-CHP group than in the R-CHOP group (76.7% [95% confidence interval (CI), 72.7 to 80.8] vs. 70.2% [95% CI, 65.8 to 74.6] at 2 years; stratified hazard ratio for progression, relapse, or death, 0.73 by Cox regression; 95% CI, 0.57 to 0.95; P=0.02). Overall survival at 2 years did not differ significantly between the groups (88.7% [95% CI, 85.7 to 91.6] in the pola-R-CHP group and 88.6% [95% CI, 85.6 to 91.6] in the R-CHOP group; hazard ratio for death, 0.94; 95% CI, 0.65 to 1.37; P=0.75). The safety profile was similar in the two groups.ConclusionsAmong patients with previously untreated intermediate-risk or high-risk DLBCL, the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP. (Funded by F. Hoffmann–La Roche/Genentech; POLARIX ClinicalTrials.gov number, NCT03274492.)

First-Line Treatment with R-CHOP Vs Dose-Adjusted R-EPOCH for Double-Expressor Lymphoma: A University of California Hematologic Malignancies Consortium Retrospective Analysis

First-Line Treatment with R-CHOP Vs Dose-Adjusted R-EPOCH for Double-Expressor Lymphoma: A University of California Hematologic Malignancies Consortium Retrospective Analysis

A randomized phase 2/3 study of R-CHOP vs CHOP combined with dose-dense rituximab for DLBCL: the JCOG0601 trial

AbstractRituximab plus cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) is the standard of care for untreated diffuse large B-cell lymphoma (DLBCL). However, the schedule for rituximab administration has not been optimized. To compare standard R-CHOP with CHOP plus dose-dense weekly rituximab (RW-CHOP) in patients with untreated DLBCL, we conducted a phase 2/3 study (JCOG0601, jRCTs031180139). Patients were randomly assigned to R-CHOP (CHOP-21 with 8 doses of rituximab once every 3 weeks [375 mg/m2]) or RW-CHOP (CHOP-21 with 8 doses of weekly rituximab [375 mg/m2]) groups. The primary end point of the phase 2 component was percent complete response (%CR) of the RW-CHOP arm, whereas that of the phase 3 component was progression-free survival (PFS). Between December 2007 and December 2014, 421 untreated patients were randomly assigned to R-CHOP (213 patients) or RW-CHOP (208 patients). The %CR in the RW-CHOP arm was 85.3% and therefore met the prespecified decision criteria for the phase 2 component. With a median follow-up of 63.4 months, the 3-year PFS and overall survival were 79.2% and 88.7% in the R-CHOP arm and 80.3% and 90.4% in the RW-CHOP arm, respectively. There was no significant difference in PFS (hazard ratio, 0.95; 90.6% confidence interval, 0.68-1.31). Although the safety profile and efficacy of RW-CHOP was comparable with R-CHOP and its tolerability was acceptable, weekly rituximab in combination with CHOP during the early treatment period did not improve PFS in untreated patients with DLBCL. This trial was registered at jrct.niph.go.jp as #jRCTs031180139.

Immunohistochemical Markers of Tumor Microenvironment as Prognostic Predictors in Diffuse Large B-Cell Lymphoma: Study from an Oncology Centre in South India

Introduction Diffuse large B-cell lymphoma (DLBCL) accounts for 60% of lymphomas in India. Although the survival of DLBCL patients has improved following the addition of rituximab, a subset of patients do not respond well to therapy. Among the several factors responsible for this varied response, tumor microenvironment is considered to be crucial. This study is a search for such prognostic markers in the tumor microenvironment. Materials and Methods A total of 97 patients were selected, of whom 34 were treated with the CHOP regimen and 63 with RCHOP. Immunohistochemistry for CD68 was performed to study the stromal-1 signature and CD34 for stromal-2 signature. Results There was a significant increase in the counts of CD68-positive cells among patients free of events. CD34 count was higher in patients with events in both CHOP and RCHOP groups. Conclusion Additional assessment of stromal microenvironment along with the cell of origin might predict the clinical outcome better in DLBCL.