Toxicity and tolerability of DA-EPOCH-R for aggressive lymphomas in the elderly: A retrospective cohort study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20030-e20030
Author(s):  
Shanley Banaag ◽  
Manish Singla ◽  
Mary Kwok ◽  
Dechang Chen

e20030 Background: There remain concerns regarding appropriate patient selection for dose-adjusted EPOCH-R in the treatment of lymphoma, particularly diffuse large B-cell lymphoma, where efficacy is comparable to R-CHOP but significantly more toxic. As the average age at diagnosis of DLBCL is between 60-70 years old, ability of elderly patients to complete and tolerate therapy is critical in treatment decision. Our aim was to investigate the differences in tolerability and toxicity of DA-EPOCH-R among different age groups. Methods: We conducted a retrospective review of patients treated with DA-EPOCH-R at Walter Reed National Military Medical Center. The institutional pharmacy database was queried to identify adult patients diagnosed with lymphoma and treated with DA-EPOCH-R from July 2005 through March 2018. Chart reviews were performed and information on dose reductions, delays, and adverse treatment effects were recorded and stratified between patients aged < 45 years, 45-59, 60-74 and ≥75 years. Results: 70 patients were identified for review. Average age was 55.8 +/- 15.5 years; 49% of patients were ≥ 60 years, including 9 patients who were ≥ 75 years. Diagnoses included diffuse large B-cell lymphoma (n = 46), transformed lymphoma (n = 12), primary mediastinal B-cell lymphoma (n = 4), Burkitt lymphoma (n = 3), T-cell lymphoma (n = 3), and high-grade B-cell lymphoma, NOS (n = 2). There was no significant difference in the median number of cycles completed between the age groups ( p= 0.2540). However, there was a significant difference in the maximum dose level achieved ( p= 0.0003). The median dose level achieved was 3.4 for patients age < 45 (range 1-5), 2.5 for patients age 45-59 (range 1-5), 1.88 for patients age 60-74 (range 1-4), and 0.88 for patients age ≥75 (range -2 to 2). Patients greater than 60 years were more likely to have any dose delay ( p= 0.001), more total dose delays (p = 0.004), and to experience gastrointestinal (GI) toxicities ( p= 0.014). There were no significant differences seen in peripheral neuropathies ( p= 0.425) nor hospitalizations ( p= 0.242). One patient passed away due to toxicity. Conclusions: This study demonstrates the use of DA-EPOCH-R in a real-world setting for the treatment of aggressive lymphomas. Our data suggest that elderly patients can complete all planned courses of DA-EPOCH-R but do not reach the dose intensity achieved by younger patients. In addition, elderly patients are more likely to require dose delays and experience GI toxicities without significant differences in hospitalizations or peripheral neuropathy.

2015 ◽  
Vol 57 (7) ◽  
pp. 1633-1639 ◽  
Author(s):  
Nadav Sarid ◽  
Erel Joffe ◽  
Lili Gibstein ◽  
Irit Avivi ◽  
Aaron Polliack ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Di Wang ◽  
Peng Liu ◽  
Yue Zhang ◽  
Hui-Ying Liu ◽  
Di Shen ◽  
...  

Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is a common subtype of non-Hodgkin’s lymphoma and is very likely to infiltrate the bone marrow. Over 30% of patients are converted to relapsed/refractory DLBCL after first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, with a poor prognosis. Our aim was to identify molecular markers that might be utilized to predict relapsed/refractory ABC-DLBCL patients. Hence, we collected bone marrow aspirate smears from 202 patients with ABC-DLBCL and detected expression of bone marrow molecular marker proteins by immunocytochemistry. Signal transducer and activator of transcription (Stat)3, nuclear factor (NF)-κB p65, Syk, Bruton’s tyrosine kinase (BTK), and Bcl2 proteins were strongly expressed in bone marrow aspirate smears of ABC-DLBCL patients. The same smear could present positive expression of multiple proteins simultaneously. Positive combinations of protein expression were associated with resistance. The most significant finding was that the Stat3+NF-κB+ group developed resistance, which was significantly higher than that of the Stat3-NF-κB-group (80 vs. 14%). There was a significant difference in two-year relapse-free survival between protein-positive and protein-negative combinations of Stat3-NF-κB (P = 0.005), Bcl2-Stat3 (P = 0.009), Bcl2-Pax5 (P = 0.003), and BTK-Syk (P < 0.001). Thus, we detected key molecules in multiple signaling pathways in bone marrow aspirate smears. At the same time, the results provide further clinical evidence of ABC-DLBCL drug-resistant molecules and provide a theoretical basis for rational second-line treatment after drug resistance.


Blood ◽  
2017 ◽  
Vol 130 (20) ◽  
pp. 2180-2185 ◽  
Author(s):  
Richard J. Lin ◽  
Madhusmita Behera ◽  
Catherine S. Diefenbach ◽  
Christopher R. Flowers

Abstract Survival outcome for elderly patients with newly diagnosed diffuse large B-cell lymphoma remains suboptimal in the rituximab era. In this systematic review, we summarize available evidence relevant to the inclusion of anthracycline in upfront chemoimmunotherapy for these elderly patients and highlight the need of prospective clinical trials. With limited prospective data, we find that pretreatment comprehensive geriatric assessment accurately predicts survival and treatment-related toxicities, suggesting its potential role in guiding overall treatment decision-making.


2016 ◽  
Vol 136 (2) ◽  
pp. 76-84 ◽  
Author(s):  
Eva González-Barca ◽  
Miguel A. Canales ◽  
Antonio Salar ◽  
Secundino Ferrer ◽  
Eva Domingo-Domenech ◽  
...  

Background/Aims: Rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 14 days seems to achieve better outcomes than R-CHOP every 21 days in diffuse large B-cell lymphoma (DLBCL) patients. Currently, the standard regimen is R-CHOP every 21 days. Methods: This is a phase II clinical trial of treatment with 6 cycles of R-CHOP-14 with pegfilgrastim support in 2 populations of previously untreated DLBCL patients aged ≥65 years (n = 73) or <65 years (n = 51) with low-risk International Prognostic Index scores (0-2). Results: With a median follow-up of 63.7 months, the 5-year event-free survival rate was 53.8% in patients aged ≥65 years and 71.0% in patients aged <65 years. The 5-year overall survival rate was 71.4 and 89.8%, respectively. The complete remission rate was 69.9% for older and 80.4% for younger patients. The median relative dose intensity of cytotoxic drugs was 143.2% in the elderly and 149.1% in the young patients. Febrile neutropenia was the most common grade 3-4 adverse event, being higher in elderly patients (21.3 vs. 9.3%). Eight deaths (7 in elderly patients) were considered treatment related. Conclusion: In conclusion, the R-CHOP-14 regimen is feasible and very active, though it is more toxic in elderly patients mainly due to an increased incidence of infections. New strategies, such as new monoclonal antibodies or new targeted therapies, are needed to improve the outcomes of DLBCL patients.


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