Primary non-Hodgkin’s lymphoma of the orbit: treatment outcomes from India

Background: Primary non-Hodgkin’s lymphoma (NHL) of the orbit is rare. Orbital NHLs show good response to both radiotherapy (RT) and chemotherapy, and hence, the emphasis should be to ensure maximum cure rate with minimum morbidity. In this study, we present the clinical profile and treatment outcomes of patients with NHL who had initial presentation in the orbit. Materials and methods: In this retrospective analysis, case records of patients with a diagnosis of NHL of the orbit were analysed from January 2005 to January 2015. Patients were worked up and staged according to the Ann Arbor system. Patients with large tumours were initially given chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin and prednisolone) three weekly for 4–6 cycles. Patients with residual disease were given RT 20–30 Gy at 2 Gy per fraction. RT when given as a primary treatment consisted of 36–45 Gy at 1·8–2 Gy per fraction on either Cobalt 60 machine or linear accelerator. Results: A total of 52 patients with diagnosis of orbital NHL were included in this study. Median age at presentation was 57 years (range 13–71). Left, right and bilateral orbit was involved in 21 (40%), 28(54%) and 3(6%) patients, respectively. Low- and high-grade pathology was seen in 39(75%) and 13(25%) patients, respectively. On immunohistochemistry, 23(44%) tumors were CD 20 positive. After staging, 33 (63%) patients had stage I disease. Median tumour size was 4·0 × 3·2 × 1·5 cm (1·7 × 1·7 × 1·4 cm to 5·8 × 4·0 × 4·7 cm). Primary RT was given to 7(13%) patients. Upfront chemotherapy was given in 45(86·5%) patients, out of which 24 had stage I disease. RT consolidation was done in 26 (50%) patients for residual disease after chemotherapy. Median follow-up was 88 months (range 29–183 months). Relapse occurred in 6(9·6%) patients; 2 local; 2 local + distant and in 2 distant alone. These patients were successfully salvaged with systemic chemotherapy and local RT. One patient died due to neutropenia. Overall survival in this series was 96%. Conclusions: Excellent local control was achieved with initial chemotherapy followed by RT for primary orbital NHL with minimal toxicity. We recommend a dose of 36–40 Gy for definitive RT and 30 Gy for lymphoma following chemotherapy using 2 Gy/fraction for Indian patients who present with bulky tumours. RT should be incorporated in treatment of orbital NHL whenever possible as it is safe, effective and is associated with minimal complications.

Diffuse Large B-Cell Lymphoma in the Elderly : Retrospective Analysis from a Single Tertiary Cancer Center in India

Introduction Diffuse large B-cell lymphoma (DLBCL) commonly affects the elderly population and the treatment is often challenging because of the close interplay between age, comorbidities, frailty as well as cognitive and psychosocial factors. Anthracycline constitutes the cornerstone of the treatment regimen of Non-Hodgkin lymphoma but is associated with several side-effects including cardiotoxicity. At our institute, we replace doxorubicin with etoposide in cases where compromised cardiac function, performance status (PS) and multiple comorbidities are major concerns. We aim to retrospectively analyze the treatment outcomes of patients with DLBCL aged ≥ 60 years and specifically compare R-CHOP and R-CEOP regimens. Methods In this retrospective study, we included patients aged ≥ 60 years, newly diagnosed with DLBCL according to WHO classification between January 2015 to December 2018 at our center. Chemotherapy regimens received included R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone), R-CE (Etoposide) OP for anthracycline-ineligible or elderly frail patients and R-EPOCH, followed by radiotherapy for residual disease or bulky sites (size > 7cm). The decision to use anthracycline or non-anthracycline based regimen was at the discretion of the physician depending on the performance status, frailty and serum albumin levels. Dose of etoposide used in the R-CEOP regimen was 65mg/m 2 orally on day 1-3. Primary G-CSF prophylaxis was used in all patients. After 4 cycles of chemotherapy, patients underwent an interim PET-CT for response evaluation. Patients who attained partial response underwent a repeat PET-CT evaluation at the end of 6 cycles. Post treatment completion, patients were followed up for clinical examination every three months for the first two years, six monthly for the next three years and annually thereafter. Results A total of 218 patients were included. The median age of patients was 65 years (range, 60-88 years). Patients were divided into two age-groups with 124 patients (56.9%) of the age group of 60-65 years and 94 patients (43.1%) were aged above 65 years. Of the 218 patients, 71 patients (32.6%) received R-CHOP regimen and 137 patients (62.4%) received R-CEOP regimen, while 10 patients (5.0%) received R-EPOCH. More patients aged >65 years received R-CEOP than in the 60-65 years age group (83% vs 47.6%) and the difference was statistically significant (p-value <0.001). Reasons for replacing doxorubicin were cardiac contraindications (9.6%), presence of hypertension or ≥ 2 significant comorbidities (29.9%), advanced age (age ≥ 75 years, 8.0%), baseline Eastern Cooperative Oncology Group (ECOG) PS of > 2 (3.6%), and physician's discretion in 48.9% of cases. Baseline disease characteristics including NCCN-IPI of patients treated with both these regimens were comparable. Complete response rate and overall response rate were higher in the R-CHOP group compared to the R-CEOP group, but statistically significant difference was found only among 60-65 years of age group. Among patients aged 60-65 years, the incidence of febrile neutropenia and grade III/IV hematological toxicities were significantly higher in the R-CHOP group than in the R-CEOP group. The overall median follow-up was 22.71 months (Range 1-81 months). The 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 <0.001) (Figure 1). This statistically higher 2-year PFS rate was found among patients with early as well as advanced stage disease, and also in the age group of 60-65 years (Figure 2, 3). Match pairing analysis after adjusting for confounders like NCCN-IPI and presence of bulky disease showed significantly higher 2-year PFS rate in the R-CHOP group than in the R-CEOP group (70.0% vs 34.6%, p-value <0.001). ECOG PS at presentation, NCCN-IPI and the chemotherapy regimen were found to be significant factors for PFS by multivariate analysis (Table 1). Conclusion Age and comorbidities are not absolute contraindications to the use of anthracyclines. Fit patients without cardiac contraindications should receive R-CHOP regimen whenever possible. Geriatric assessment tools should be used for the frail or unfit patients to guide appropriate therapy and further prospective trials should be done in this direction. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

High Toxicity and Poor Survival with Association CHOP Plus Etoposide Compared to CHOP Regimen in 124 Brazilian Patients with Nodal PTCL Lymphomas (nPTCL): A Real-Life Experience

Introduction: Nodal PTCL constitute a heterogeneous group of rare malignancies derived from CD4+ T-helper, CD8+ T-cytotoxic or follicular T-helper lymphocytes. It presents aggressive clinical-biological behavior and distinct outcomes [1]. These tumors have significant geographic variation, making important studies of clinical and epidemiological characteristics and outcomes of patients in specific areas of the word. Latin American data on nPTCL are scarce in the literature [2] and its first-line treatment is still controversial and ineffective, due to high rates of primary chemo-resistance. Therefore, this study aims to describe clinical, laboratory and epidemiological characteristics, identify prognostic factors and analyze the outcomes of patients with nPTCL treated with CHOP/CHOP-like regimens as first-line therapy in Brazil. Methods: This is a retrospective, observational and unicentric study involving 124-Brazilian patients with nPTCL treated at HC/FMUSP from January 2000 to December 2017. All cases were submitted to centralized histopathological review and classified according to WHO-2016 criteria on PTCL/NOS, AITL, ALK+/ALCL or ALK-/ALCL. Clinical-laboratory and outcomes data were obtained from digital medical records. Descriptive variables were arranged in absolute numbers and relative frequencies. OS and PFS curves were estimated by the Kaplan-Meier method. Univariate Cox analysis was used to determine factors with prognostic impact through the association between categorical variables and survival curves. Variables that were significant in the univariate analysis were tested in a multivariate analysis to establish independent variables. Statistical analysis was performed using SPSS V.22 software and p-values ≤ 0.05 were considered statistically significant. Results: The clinical-laboratory characteristics of 124 nPTCL patients were summarized in Table 1. With a median age of 48.5 years (18-87 years) and 57.3% of male, about 81.5% had B-symptoms, 88.7% with CS III/IV and 58.1% had IPI ≥ 3. ORR to first-line treatment was 58.9%, 37.9% (47/124) were treated with CHOP regimen and 35.5% (44/124) with CHOEP, 30.1% (37/124) were submitted to radiotherapy and 32.3% (40/124) were consolidated with ASCT. We observed a higher 2-year OS for patients treated with CHOP versus CHOEP (78.7% vs. 61.4%; p=0.05), as well as a better 2-year PFS for the same regimen (69.7% vs. 25.0%; p<0.0001) - Figure 1. CHOEP treatment was associated with higher rates of G3-4 neutropenia, febrile neutropenia and G3-4 thrombocytopenia (57% x 88% p=0.001, 38% x 70% p=0.003 and 27% x 63% p=0.0007, respectively). Overall mortality was 55.6% (69/124) during all follow-up, with disease progression being the major cause of death (29/69 - 42.0%). With a median follow-up of 23.7 months (0.10-278.6 months), medians of OS and PFS were 48.0 months (95% CI: 9.0-86.9) and 8.8 months (95% CI: 3.9-13.7), respectively. Estimative of 2-year OS and PFS for the global cohort were 61.3% and 41.5%, respectively. In the univariate analysis, factors with a favorable prognostic impact on OS were: IPI < 3 (HR: 0.30; 95% CI: 0.15-0.58; p<0.0001), absence of bone marrow infiltration (HR: 0.39; 95% CI: 0.20-0.75; p=0.005), LDH < 480 U/L (HR: 0.36; 95% CI: 0.19-0.68; p=0.002), radiotherapy (HR: 0.23; 95% CI: 0.10-0.55; p=0.001) and ASCT (HR: 0.28; 95% CI: 0.004-0.30; p<0.0001). Factors associated with better 2-year PFS were: IPI < 3 (HR: 0.36; 95% CI: 0.18-0.71, p=0.004), absence of bone marrow infiltration (HR: 0.30; 95% CI: 0.26-0.55; p=0.03 ), LDH < 480 U/L (HR: 0.36; 95% CI: 0.19-0.67; p=0.001), radiotherapy (HR: 0.17; 95% CI: 0.06-0.44; p<0.0001) and ASCT (HR: 0.03 ; 95% CI: 0.004-0.23); p=0.001). In the multivariate analysis, factors associated with better 2-year OS were: LDH < 480 U/L (HR: 0.40; 95% CI: 0.21-0.76); p=0.005) and ASCT (HR: 0.47; 95% CI: 0.006-0.34; p=0.003). LDH < 480 U/L (HR: 0.45; 95% CI: 0.23-0.87; p=0.01) and ASCT (HR: 0.07; 95% CI: 0.01-0.54; p=0.01) were also associated with higher 2-year PFS. Conclusion: This is the largest real-life Latin American nPTCL cohort published to date. Patients with nPTCL have poor survival and high rate of chemo-resistance. In our cohort, adding etoposide to the CHOP regimen showed no survival benefit and was associated with high toxicity. Normal values of LDH and consolidation with ASCT were independent factors associated with better outcomes in Brazilian patients with nPTCL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Risk of Febrile Neutropenia in Very Elderly Patients Aged ≥80 Years Who Received R-CHOP Regimen: A Nationwide Analysis in Japan

Background: Despite the aging society, few studies have evaluated risk factors for febrile neutropenia (FN) in the very elderly. This may be due to the difficulty of conducting a prospective study in the presence of comorbidities and a limited number of patients. We retrospectively analyzed risk factors for FN in the first cycle of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP) regimen in the very elderly aged ≥ 80 years using a nationwide inpatient database in Japan. Study Design and Methods: This study was a retrospective cohort study using the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan. The database includes discharge abstracts and administrative claims data from >1200 acute-care hospitals and covers around 90% of all tertiary-care emergency hospitals in Japan. We identified patients aged ≥ 80 years old with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who received the first cycle of R-CHOP regimen between July 2007 and March 2017 from the database. The initial dose intensity (IDI, %) was calculated as the average ratio of the actual dose to the 100% dose of cyclophosphamide and doxorubicin. IDI less than 80% was defined as reduced IDI. Multivariable logistic regression analysis fitted with a generalized estimating equation accounting for within-hospital clustering was performed to identify factors associated with the occurrence of FN. P<0.05 was considered statistically significant. Results: We identified 1,819 patients aged ≥ 80 years old with DLBCL who were newly diagnosed and treated with R-CHOP. The median age was 83 years (interquartile range: 82-85). A total of 73 (4%) patients received antimicrobial prophylaxis, and 270 (15%) received primary prophylaxis with G-CSF. Reduced IDI of R-CHOP regimen was performed in 1,444 (79%) patients, including 697 patients with 60-80% of IDI and 747 patients with 40-60% of IDI. FN occurred in 115 of the 1,819 patients (6.3%) with a median of 10 days (interquartile range: 8-12) after the administration of cyclophosphamide. Antimicrobial prophylaxis, primary prophylaxis with daily G-CSF, and pegfilgrastim were not significantly associated with a lower occurrence of FN in the very elderly patients (odds ratio 0.69 [95% confidence interval 0.30-2.21], 1.39 [0.73-2.64], 1.43 [0.73-2.81], respectively). Reduced IDI was significantly associated with a lower occurrence of FN (40-60%: odds ratio 0.54 [0.32-0.92]). Advanced-stage lymphoma (>stage 2) and placement of central venous catheter was significantly associated with the occurrence of FN (odds ratio 1.59 [1.02-2.49], 3.19 [1.81-5.62], respectively). Conclusion: The present nationwide study showed that IDI was reduced in most of the very elderly patients with DLBCL in a real-world clinical practice. The proportion of the very elderly patients who developed FN tended to be lower than those in previous studies with younger patients, which may be explained by reduced IDI in the very elderly. Whereas, prevention strategies with G-CSF for FN may be less effective in the very elderly. Disclosures Matsuda: Ono Pharmaceutical: Other: Lecture fee; Kyowa Kirin: Other: Lecture fee. Jo: Tsumura: Other: Lecture fee, Research Funding; AstraZeneca: Other: Lecture fee; Sanofi: Other: Lecture fee; Boehringer Ingelheim: Other: Lecture fee. Shimura: Eisai: Other: Lecture fee. Honda: Otsuka Pharmaceutical: Other: Lecture fee; Ono Pharmaceutical: Other: Lecture fee; Nippon Shinyaku: Other: Lecture fee; Jansen Pharmaceutical: Other: Lecture fee; Chugai Pharmaceutical: Other: Lecture fee; Takeda Pharmaceutical: Other: Lecture fee. Masamoto: MSD K.K.: Speakers Bureau; Eisai Co., Ltd.: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Takeda Pharmaceutical Company Limited.: Speakers Bureau; Chugai Pharmaceutical Company: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Nippon Shinyaku Co., Ltd.: Speakers Bureau; AbbVie GK: Speakers Bureau; Janssen Pharmaceutical K.K.: Speakers Bureau; SymBio Pharmaceuticals: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Yasunaga: Pfizer: Consultancy, Other: Lecture fee; Novartis: Consultancy, Other: Lecture fee; Boehringer Ingelheim: Other: Lecture fee; Chugai Pharmaceutical: Other: Lecture fee; Tsumura: Other: Lecture fee. Kurokawa: MSD K.K.: Research Funding, Speakers Bureau; Eisai Co., Ltd.: Research Funding, Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Research Funding, Speakers Bureau; Takeda Pharmaceutical Company Limited.: Research Funding, Speakers Bureau; Chugai Pharmaceutical Company: Research Funding, Speakers Bureau; Daiichi Sankyo Company.: Research Funding, Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Research Funding, Speakers Bureau; AbbVie GK: Research Funding, Speakers Bureau; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding, Speakers Bureau; Nippon Shinyaku Co., Ltd.: Research Funding, Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau; Teijin Limited: Research Funding, Speakers Bureau; Pfizer Japan Inc.: Research Funding, Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Research Funding, Speakers Bureau.

Clinical Analysis of 15 Cases of Non-Hodgkin Lymphoma Complicated with Pneumocystis carinii Pneumonia Treated with R-CHOP Regimen

Objective: To investigate the clinical features of R-CHOP regimen in the treatment of non-Hodgkin’s lymphoma with Pneumocystis carinii pneumonia (PCP) in order to improve the understanding of PCP and the side effects of Rituxan. Methods: A retrospective analysis of 90 patients with non-Hodgkin’s lymphoma treated with R-CHOP chemotherapy in our hospital from November 2015 to November 2020, of which 15 (16.7%) patients, combined with PCP clinical data, including clinical symptoms, physical signs, chest imaging examination and treatment data were used for to analysis and summarization. Results: The clinical features of R-CHOP chemotherapy combined with PCP were fever, cough, and sputum. Some patients had fewer clinical symptoms. Common imaging manifestations were double lung membrane glass shadow, patchy shadow, and flocculent shadow. It can occur in all clinical stages, and the incidence of late stage is high, and there is no clear correlation with bone marrow suppression. Pneumocystis was found in 2 cases of sputum, and the rest of the patients were clinically diagnosed. The main therapeutic drugs are sulfamethoxazole (8/15), compound sulfamethoxazole (6/15), clindamycin (1/15, sulfa drug allergy), and adrenal cortex hormones (4/15). Fourteen cases were cured and 1 case died. Conclusion: The incidence of R-CHOP in advanced non-Hodgkin’s lymphoma of PCP is high. Patients with clinical use of R-CHOP chemotherapy will encounter fever, cough, chest computed tomography (CT) film glass shadow, and diffuse patch shadow. Patients should be alert to the possibility of PCP and take sulfonamides as soon as possible for medical treatment.

Testicular non-Hodgkin’s lymphoma – a rare tumor

Primary lymphoma of the testis is an exceedingly rare disease. We present a case of a 65 years old gentleman who presented with a brief history of testicular pain. Imaging studies and serum tumour markers indicated a testicular lesion of suspicious aetiology. High inguinal orchidectomy was performed. Histopathology and immunohistochemistry revealed diffuse large B-cell lymphoma. Positron emission tomography (PET) scan revealed a metabolically active retroperitoneal lymph node in aortocaval location. Subsequently he underwent chemotherapy with Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen plus intravenous Methotrexate, following which PET scan showed disappearance of the previously detected metabolically active lesion.