Reduced Corticosteroid Exposure Is Safe and Does Not Reduce Disease Control among Hodgkin Lymphoma Patients Treated with Escalated BEACOPP (eBEACOPP).

Background and Objectives: eBEACOPP is the most effective chemotherapy regimen for younger patients with early unfavorable (EU) and advanced-stage (AS) Hodgkin lymphoma (HL), albeit with significant toxicities. The 14-day/cycle prednisone course contributes to side effects, including osteoarticular events like avascular bone necrosis (AVN). Our center has been using eBEACOPP since 2009 for AS and 2014 for EU patients. In 2016, we reduced prednisone treatment to 7-10 days to lessen AVN risk. We analyzed the effects of this approach. Materials and Methods: We retrospectively collected data on patients who received at least two cycles of eBEACOPP for first-line HL treatment. Results: A total of 162 patients (33 EU, 129 AS) were included. Their median age was 31 (range 19-59 years), and 88 were males. A total of 94 patients received full corticosteroid courses, and 68 received reduced corticosteroid courses. The overall response rate (ORR) was 98%. Different corticosteroid dosings had no significant effect on ORR, febrile neutropenia episodes, or hospital admissions. After a median follow-up (mFU) of 58 months, the 5yPFS for the entire cohort was 98% vs. 95% for the standard course vs. the short corticosteroids course, respectively (p = 0.37), while the 5yOS was 98% vs. 99% for the standard course vs. short corticosteroids course, respectively (p = 0.87). In AS patients intended to be treated with six eBEACOPP cycles, 5yPFS and 5yOS were 100% vs. 97% and 100% vs. 99% for standard vs. short corticosteroid courses, respectively (p = 0.56 and p = 0.17). In EU patients, 5yPFS was 97% (standard) vs. 95% (short) (p = 0.98) and 5yOS 100% vs. 93.3% (p = 0.87). Osteoarticular events were numerically lower in patients receiving the shorter prednisone course, both in the whole cohort and in the subgroup of patients treated with six cycles of eBEACOPP, but this difference failed to reach statistical significance. Conclusions: eBEACOPP provides excellent and durable first-line disease control. Shortening the corticosteroid course does not compromise efficacy, potentially reducing toxicity. However, longer follow-ups and larger studies are needed for confirmation.

Long-Term Results of IFRT vs. ISRT in Infradiaphragmal Fields in Aggressive Non-Hodgkins's Lymphoma Patients-A Single Centre Experience.

(1) Background: This study aimed to examine the difference in efficacy and toxicity of involved-field (IFRT) and involved-site radiotherapy (ISRT) fields in infradiaphragmal aggressive non-Hodgkin lymphoma patients. (2) Methods: In total, 140 patients with infradiaphragmal lymphoma treated between 2003 and 2020 were retrospectively evaluated. There were 69 patients (49%) treated with IFRT, and 71 (51%) patients treated with ISRT. The median dose in the IFRT group was 36 Gy, (range 4-50.4 Gy), and in the ISRT group, it was 30 Gy (range 4-48 Gy). (3) Results: The median follow-up in the IFRT group was 133 months (95% CI 109-158), and in the ISRT group, it was 48 months (95% CI 39-57). In the IFRT group, locoregional control was 67%, and in the ISRT group, 73%. The 2- and 5-year overall survival (OS) in the IFRT and ISRT groups were 79% and 69% vs. 80% and 70%, respectively (p = 0.711). The 2- and 5-year event-free survival (EFS) in the IFRT and ISRT groups were 73% and 68% vs. 77% and 70%, respectively (p = 0.575). Acute side effects occurred in 43 (31%) patients, which is more frequent in the IFRT group, 34 (39%) patients, than in the ISRT group, 9 (13%) patients, p > 0.01. Late toxicities occurred more often in the IFRT group of patients, (10/53) 19%, than in the ISRT group of patients, (2/37) 5%, (p = 0.026). (4) Conclusions: By reducing the radiotherapy volume and the doses in the treatment of infradiaphragmatic fields, treatment with significantly fewer acute and long-term side effects is possible. At the same time, efficiency and local disease control are not compromised.

Glomerular filtration rate is an independent prognostic factor in patients with B-large cell lymphoma.

Chronic kidney dysfunction is associated with increased mortality in multiple cancer types. Preliminary evidence suggests the same to be true for B-large cell lymphomas (B-LCL). To analyze the relationship of glomerular filtration rate (GFR) and outcome of B-LCL in detail we collected data on outcomes of 285 consecutive patients with newly diagnosed B-LCL treated at our institution with standard rituximab-containing regimens who did not have preexisting kidney disease or urinary tract obstruction at presentation. Median age was 59, range 18 to 87, 145 were male and 140 females. Forty-four had GFR < 60 mL/min, 123 had 60 to 90 mL/min, and 118 > 90 mL/min. Median follow-up of surviving patients was 49 months and estimated 3-year survival 76%. In univariate analysis age (P < .001), GFR (P = .014), stage (P < .001), performance status (P = .044), chemotherapy regimen (P < .01), and international prognostic index (IPI) (P < .001) were statistically significant prognostic factors. In multivariate analysis, age and GFR remained the only independent prognostic factors. Subtracting 1 from the IPI score of patients who had GFR > 90 mL/min and IPI > 1 resulted in a prognostic index that divides patients into 3 prognostic groups (low risk = 0-1, intermediate risk = 2-3 and high risk = 4-5) with an acceptable patient distribution frequency (38%, 39%, and 23%, respectively) and improved statistical significance and separation in comparison to IPI (5-year survival rates of 92%, 74%, and 42%, respectively). GFR is an important independent prognostic factor for B-LCL that should be taken into account in clinical decision making and data analysis and probably be incorporated in prognostic indices.

Efficacy and toxicity of infradiaphragmal radiotherapy fields in lymphoma patients: a single-centre experience.

PURPOSE: Data on efficacy and toxicity of infradiaphragmal radiotherapy fields in lymphoma patients are scarce. We therefore performed this retrospective study to analyse our experience with radiotherapy exclusively to infradiaphragmal fields. MATERIALS AND METHODS: we retrospectively evaluated 101 patients treated between 2003 and 2014. Median dose was 36 Gy, range 4 to 54 Gy. Medium dose per fraction was 2 Gy, range 1.5 to 7 Gy. RESULTS: After a median follow-up of 66 months (range 1-211 months), we observed lymphoma recurrence in 38 patients (38%), five in the RT field and 33 out-of-field. Recurrences were significantly more frequent in the salvage group (17 out-of-field and 4 in-field in 31 patients) than in adjuvant group (16 out-of-field and 1 in-field in 70 patients; p < 0.001). The 2-, 5- and 10-year event-free survival (EFS) rates were 62%, 56% and 54%. The 2-, 5- and 10-year overall survival (OS) rates for the entire group of patients are 73%, 60% and 54%, respectively. Acute side effects occurred in 43 (43%) patients, most frequent gastrointestinal in 26 (26%) patients. Late side effects occurred in 12 (12%) of all patients, 6 of 23 (26%) followed up for more than 10 years. Six patients developed secondary cancers, four gastrointestinal disturbances, two diabetes mellitus and three renal failure. CONCLUSION: Radiotherapy is an effective and safe treatment option for patients with infradiaphragmatic lymphoma providing excellent local disease control with minimal late toxicity. Infradiaphragmatic lymphoma localization should not be regarded as a contraindication for use of radiotherapy. However, patients should be monitored for a secondary malignancy.

R-CHOEP14 in younger high-risk patients with large B cell lymphoma: an effective front-line regimen with cardiac toxicity: a real-life, single-center experience.

Currently, there is no consensus regarding optimal front-line treatment for younger high-risk patients with large B cell lymphoma. American recommendations list only R-CHOP as standard, while European also include R-ACVBP and R-CHOEP14. We have been routinely using the latter regimen at our institution since 2011 and performed this retrospective real-life single-center study to analyze outcomes. Between September 2011 and April 2019, 66 newly diagnosed patients aged 18 to 60 years with B-large cell lymphoma and high-risk age-adjusted International Prognostic Index score were scheduled to receive 6 or 8 cycles of bi-weekly chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, etoposide, steroids, and rituximab (R-CHOEP14). After a median follow-up of 4.7 years, the estimated 3-year progression-free survival was 87% (95% CI 80-96%) and 3-year overall survival 90% (95% CI 83-98%). Grade ≥ 3 hematological side effects occurred in 83% and infectious in 41% of patients; one patient died of toxicity. Grade ≥ 2 cardiac toxicity occurred in 21% of patients, more frequently than previously reported. The cumulative 5-year risk of congestive heart failure with all-cause mortality as the competing risk was 17%. R-CHOEP14 is a very effective and manageable regimen for younger high-risk patients with B-large cell lymphoma, but the risk of cardiotoxicity warrants further investigations.

INFRADIAPHRAGMAL RADIOTHERAPY IN PATIENTS WITH LYMPHOMA: VOLUME DEFINITION AND SIDE EFFECTS.

- Lymphomas are very radiosensitive and radiotherapy (RT) was the first treatment modality that enabled cure. It is the most effective single modality for local control of lymphomas. However, as a local form of treatment, curative intention is only possible if all lymphoma tissue can be incorporated in the volume to be irradiated with the prescribed total irradiation dose. That is why RT is a single modality only in early stage of nodular lymphocyte predominance Hodgkin's lymphoma and low grade non-Hodgkin's lymphoma. In most patients, RT can be used as consolidation therapy after chemotherapy or as salvage after failure of chemotherapy. In the past two decades, irradiation techniques have been improved in order to spare critical tissues and reduce toxicity. Although effective, RT is a neglected modality of treatment because of the appearance of new drugs and fear of side effects after irradiation. Radiation has been shown to be effective in the treatment of all stages and forms of lymphoma. Study data are still mostly derived from patients that received supradiaphragmal RT; therefore, there is no agreement about the best management approach in patients with infradiaphragmal lymphoma.