Impact of Reduced Dose Intensity for Elderly Patients with Diffuse Large B-CELL Lymphoma Receiving R-CHOP Every 14 or 21 Days: An Analysis of the LNH03–6B GELA Study.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2723-2723
Author(s):  
Richard Delarue ◽  
Herve Tilly ◽  
Gilles Salles ◽  
Catherine Thieblemont ◽  
Nicolas Mounier ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Median Dose ◽  
Reduced Dose ◽  
Large B Cell Lymphoma ◽  
Dose Dense ◽  
Large B Cell

Abstract Abstract 2723 Introduction: Elderly patients with diffuse large B-cell lymphoma (DLBCL) frequently receive reduced dose-intensity (DI) chemotherapy (Lyman GH et al. J Clin Oncol 2004) but impact on outcome in the era of classical or dose-dense immunochemotherapy is unknown. Final results of the LNH03–6B did not show any difference in PFS (HR: 0.99 [95%CI: 0.78–1.26]; p=0.90) and OS (HR: 0.96 [95%CI: 0.73–1.26]; p=0.75) between R-CHOP14 and R-CHOP21 (Delarue et al. ASCO 2012). Methods: Patients between 60 and 80 years old with DLBCL and aaIPI≥1 were eligible. They were randomized between R-CHOP14 and R-CHOP21 for 8 cycles. Dose-intensity (DI) was calculated for all patients for cyclophosphamide (CPM), doxorubicin (DOX) and rituximab (RTX) and patients were separated into 4 quartiles for each of these drugs. Outcome (PFS and OS) according to final DI was evaluated for all patients and in R-CHOP14 and R-CHOP21 arms. Results: 602 pts were randomized, 600 were evaluable, 304 with R-CHOP14 and 296 with R-CHOP21. Median age was 70 years. Patient characteristics were similar in both arms. The percentage of cycles administered with G-CSF was 89% in R-CHOP14 and 66% in R-CHOP21. Median interval between 2 cycles was 14 d [9–94] in R-CHOP14 arm and 21 d [15–66] in R-CHOP21 arm. Median dose-intensity was 88% in R-CHOP14 and 97% in R-CHOP21 for CPM, and 88% in R-CHOP14 and 96% for R-CHOP21 for DOX. There was no difference of median dose-intensity for CPM and DOX according to G-CSF use at C1 in R-CHOP14 arm. In the R-CHOP14 arm, the increase of DI at the end of treatment, calculated according to 3-week interval as a reference, was 133% for CPM and DOX. When separating patients in 4 quartiles according to final dose intensity, there was no impact for CPM, DOX and RTX for the entire cohort in term of PFS and OS. Moreover, decreased DI for CPM, DOX and RTX did not impact negatively PFS and OS in patients randomized in the R-CHOP14 arm. On the other hand, for patients included in the R-CHOP21 arm, PFS was negatively impacted by lower DI of CPM (p=0.02), DOX (p=0.007) and RTX (p=0.006). OS was also negatively impacted by lower DI of CPM (p=0.0002), DOX (p<0.00001) and RTX (p<0.0001). In the R-CHOP21 arm, the negative impact was pronouncedly marked when comparing patients in the first and the second quartiles with those in the fourth quartile. Conclusion: While low DI has a major impact on PFS and OS in patients who receive conventional dose immunochemotherapy, consequences for patients receiving dose-dense immunochemotherapy seem less pronounced. As a consequence, immunochemotherapy could be safely decreased for elderly patients who receive R-CHOP14 and experienced adverse events. Disclosures: No relevant conflicts of interest to declare.

Reduced-dose ICE chemotherapy ± rituximab is a safe and effective salvage therapy for fit elderly patients with diffuse large B-cell lymphoma

2015 ◽  
Vol 57 (7) ◽  
pp. 1633-1639 ◽  
Author(s):  
Nadav Sarid ◽  
Erel Joffe ◽  
Lili Gibstein ◽  
Irit Avivi ◽  
Aaron Polliack ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Salvage Therapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Reduced Dose ◽  
Large B Cell Lymphoma ◽  
Large B Cell

The impacts of initial and relative dose intensity of R-CHOP on outcomes of elderly patients with diffuse large B-cell lymphoma

2016 ◽  
Vol 58 (3) ◽  
pp. 736-739 ◽  
Author(s):  
Yusuke Kanemasa ◽  
Tatsu Shimoyama ◽  
Yuki Sasaki ◽  
Miho Tamura ◽  
Takeshi Sawada ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Relative Dose Intensity ◽  
Large B Cell Lymphoma ◽  
Large B Cell

R-CHOP14 Compared to R-CHOP21 in Elderly Patients with Diffuse Large B-Cell Lymphoma: Results of the Interim Analysis of the LNH03-6B GELA Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 406-406 ◽  
Author(s):  
Richard Delarue ◽  
Herve Tilly ◽  
Gilles Salles ◽  
Christian Gisselbrecht ◽  
Nicolas Mounier ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Interim Analysis ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Abstract Abstract 406 Introduction: In 2000, the Gela demonstrated the survival advantage of adding Rituximab to CHOP21 over CHOP21 in the treatment of diffuse large B-cell lymphoma (DLBCL) in elderly patients. Two consecutive studies from the German group have shown an improvement of survival with CHOP14 compared to CHOP21, and then after with R-CHOP14 compared to CHOP14. Here, we report the results of the planned interim analysis of the LNH03-6B, a multicentric, phase III open-label, randomized trial evaluating the efficacy of R-CHOP given every 14 days compared to R-CHOP given every 21 days, held after the inclusion of the first 202 patients, with a median follow-up of 24 months. Patients and methods: Patients between 60 and 80 years old with DLBCL and aaIPI ≥ 1 were eligible. They were randomized between two immunochemotherapy regimens combining Rituximab and CHOP given every 2 (R-CHOP14, arm A) or 3 weeks (R-CHOP21, arm B) for 8 cycles. They were subsequently randomized between a prophylactic treatment with Darbepoetin alfa and a conventional treatment of chemotherapy-induced anemia. G-CSF was given according to physician decision. The primary objective was to evaluate the efficacy of R-CHOP14 compared to R-CHOP 21 as measured by the EFS, events being defined as death from any cause, relapse for complete responders and unconfirmed complete responders, progression during or after treatment and changes of therapy during allocated treatment. Secondary objectives were OS, PFS, DFS, response rate and analysis of dose-intensity and toxicity. According to previous LNH98-5 protocol, sample size was calculated to demonstrate an improvement of 2-year EFS from 55% to 65% with R-CHOP14. Six-hundred patients, randomized 1:1 between the two treatment groups recruited over 4 years and followed for a minimum of one year, will provide 80% power at the overall 5% (2-sided) significance level to detect the expected difference. Results: In this planned interim analysis, 202 patients were randomized and 201 received study treatment, 103 with R-CHOP14 and 98 with R-CHOP21. Median age was 72 years. Patients' characteristics were similar in both groups with a slightly higher proportion of patients with aaIPI 2-3 in R-CHOP14 arm (67% vs 59%) whereas a higher proportion of patients in R-CHOP21 arm presented with B symptoms (43% vs 37%). The median interval between cycles was 15 days in R-CHOP14 group and 21 days in R-CHOP21 group; 73 patients (71%) in R-CHOP14 group and 74 patients (76%) in R-CHOP21 group completed 8 cycles without progression. In the R-CHOP14 group, the increase of dose-intensity at the end of treatment, calculated according to 3-week interval as a reference, was 125% for cyclophosphamide and doxorubicin. Ninety percent of patients treated with R-CHOP14 received G-CSF, whereas only 66% in R-CHOP21 group. Response rate (CR+CRu) was 67% in R-CHOP14 arm and 75% in R-CHOP21 arm (p=NS). The 2-year EFS was 48% in R-CHOP14 arm compared with 61% in R-CHOP21 (p=NS). A similar trend was observed for 2-year PFS (49% vs 63%), 2-year DFS (57% vs 70%) and 2-year OS (67% vs 70%) (p=NS for all). Grade 3-4 hematological toxicity was more frequent in R-CHOP14 group, with a higher proportion of patients receiving red cell or platelet transfusions and/or experiencing febrile neutropenia, resulting in higher proportion of patients hospitalized for adverse events. In contrast, there was no difference for extra-hematological grade 3-4 toxicities. Conclusions: The results of this interim analysis of the LNH03-6B trial favor treatment with R-CHOP21 in elderly patients with DLBCL, with trends toward higher efficacy and lower toxicity compared to R-CHOP14. These results should be confirmed by the final analysis, concerning the 602 patients included, planned in 2010. Disclosures: No relevant conflicts of interest to declare.

Addition of rituximab to reduced-dose CHOP chemotherapy is feasible for elderly patients with diffuse large B-cell lymphoma

2012 ◽  
Vol 69 (5) ◽  
pp. 1165-1172 ◽  
Author(s):  
Ho-Jin Shin ◽  
Joo Seop Chung ◽  
Moo-Kon Song ◽  
Seon-Kyeong Kim ◽  
Sangmin Choe ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Chop Chemotherapy ◽  
Reduced Dose ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Dose-Dense CHOP plus Rituximab (R-CHOP14) for the Treatment of Elderly Patients with High-Risk Diffuse Large B Cell Lymphoma: A Pilot Study

2006 ◽  
Vol 115 (1-2) ◽  
pp. 22-27 ◽  
Author(s):  
Luigi Rigacci ◽  
Luca Nassi ◽  
Renato Alterini ◽  
Valentina Carrai ◽  
Giovanni Longo ◽  
...  
Keyword(s):  
Pilot Study ◽  
High Risk ◽  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Dose Dense ◽  
Large B Cell

Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial

2013 ◽  
Vol 14 (6) ◽  
pp. 525-533 ◽  
Author(s):  
Richard Delarue ◽  
Hervé Tilly ◽  
Nicolas Mounier ◽  
Tony Petrella ◽  
Gilles Salles ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase 3 ◽  
Large B Cell Lymphoma ◽  
Dose Dense ◽  
Large B Cell

Pegfilgrastim as hematopoietic support for dose-dense chemoimmunotherapy with R-CHOP-14 as first-line therapy in elderly patients with diffuse large B cell lymphoma

2007 ◽  
Vol 15 (7) ◽  
pp. 877-884 ◽  
Author(s):  
Ulrich J. M. Mey ◽  
Anna Maier ◽  
Ingo G. H. Schmidt-Wolf ◽  
Carsten Ziske ◽  
Helmut Forstbauer ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma ◽  
Line Therapy ◽  
Dose Dense ◽  
Large B Cell

scholarly journals Retrospective Study of the Optimal CHOP Dose for Elderly Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4211-4211
Author(s):  
Keiko Ono ◽  
Hideki Tsujimura ◽  
Akiyasu Satou ◽  
Xiaofei Wang ◽  
Takeaki Sugawara ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Chop Therapy

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma, and the number of elderly patients with DLBCL is increasing. While rituximab plus CHOP (R-CHOP) therapy is considered as the standard first-line treatment for DLBCL, elderly patients are often frail and unable to tolerate the standard dose of R-CHOP. Fifteen years ago, we conducted a prospective study to investigate optimal reduced doses of CHOP therapy for patients aged 65-79 years and those older than 79 years. We concluded that 5/6 (83%) and 7/12 (58%) doses of standard CHOP are effective and tolerable for these two age groups, respectively (Mori M, et al. Leuk Lymphoma. 2001;41:359-66). Since then, we have applied this strategy with the standard dose of rituximab. To evaluate the efficacy and tolerability of reduced R-CHOP therapy for elderly patients, we performed a retrospective analysis. Methods: We reviewed medical records of patients aged 65 years or older with newly diagnosed DLBCL, who underwent R-CHOP therapy from August 2010 to December 2013. Intravascular large B-cell lymphoma and primary central nervous system lymphoma were excluded from this study because R-CHOP therapy alone is not considered as standard for these diseases. We calculated the relative dose intensity (RDI), dividing the actually used doses of cyclophosphamide and doxorubicin by the interval between each course compared with the standard doses (750 mg/m2 cyclophosphamide and 50 mg/m2 doxorubicin every 21 days). Results: During the study period, data were collected from 100 patients (56 males and 44 females) with a median age of 74 (65-86) years. Sixty patients had advanced stages, 40 patients had a score of at least one in the Charlson comorbidity index (Charlson ME, et al. J Chronic Dis. 1987;40:373-83), 18 patients had a poor performance status (Eastern Cooperative Oncology Group performance status: ≥2), and 14 patients were older than 79 years. The overall response rate was 93%, and the complete response (CR) rate was 81%. Three-year overall survival (3-yr OS) was 78%. In comparison with the international prognostic index (IPI), 3-yr OS was 100% (IPI: low, n=26), 94% (IPI: low-intermediate, n=17), 71% (IPI: high-intermediate, n=24), and 58% (IPI: high, n=33). Hematologically adverse events were generally tolerable. No patient experienced a grade 4 hemoglobin decrease, and only four patients experienced a grade 4 platelet decrease. Although 55 patients received granulocyte colony-stimulating factor, a grade 4 leukocyte decrease was common (n=38) and febrile neutropenia (FN) was often seen (n=21). Patients who experienced FN had a significantly shorter OS (p=0.04). With a median follow up of 44.4 months, 20 patients experienced disease progression and 15 patients died after progression. Five patients remained in CR but died of other types of cancer. The other seven patients died of other causes. The median RDI was 0.81 in patients aged 65-79 years and 0.58 in patients older than 79 years. These doses were very similar to the originally intended doses of 5/6 (0.83) for younger patients and 7/12 (0.58) for older patients. The older group tended to show shorter OS (3-yr OS: 64%). However, recurrence rates of the two groups were very similar. Conclusions: This study demonstrates that rituximab plus 5/6 or 7/12 doses of CHOP therapy are effective and tolerable for elderly patients aged 65-79 years and those older than 79 years, respectively. It is noteworthy that the prognosis of patients with an IPI score of ≤2 was very satisfactory. Based on these results, the dose intensity does not have to be increased for these low risk groups. It is possible that increasing the dose intensity in high risk (IPI score: ≥3) patients improves the outcome. However, high risk patients tend to have much tumor burden and a poor performance status. In this group, higher dose chemotherapy will also increase the risk of developing FN and might be associated with inferior OS. Treatment of frail elderly patients with high-risk DLBCL is extremely challenging, and we need to gain further experience. Disclosures No relevant conflicts of interest to declare.

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