scholarly journals In Elderly Patients with Newly Diagnosed Aggressive B-Cell Lymphoma, the Rate of Change in Body Weight after the First Course R-CHOP (-like) Chemo Therapy Has Effect on Their Survival

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4238-4238 ◽  
Author(s):  
Muramatsu Ayako ◽  
Nagata Hiroaki ◽  
Kuriyama Kodai ◽  
Hirakawa Yoshiko ◽  
Oshiro Muneo ◽  
...  
Keyword(s):  
Body Weight ◽  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Rate Of Change ◽  
Newly Diagnosed ◽  
Clinical Records ◽  
The Impact ◽  
Aggressive B Cell Lymphoma

Abstract Background The incidence of B-cell lymphoma increases with age, and over 40% occurs in patients at age of 70 years old or more. Aggressive B-cell lymphoma was often treated with R-CHOP (-like) regimen. However, in elderly B-cell lymphoma patients, treatment intensification often must be lowered due to the risks of comorbidities and organ function deterioration, and treatment outcomes are worse compared to younger patients. The optimal dose of R-CHOP (-like) therapy is necessary to improve the outcome of the elderly patients with B-cell lymphoma. We conducted a retrospective cohort study examining the influence of the rate of change in body weight after the first chemo therapy on their outcomes and survival. Methods Clinical records of 111 patients who had received R-CHOP (-like) regimen were retrospectively analyzed. They were all over 73 years old, and newly diagnosed with aggressive B-cell lymphoma by WHO 2008 criteria. They were treated at Japanese Red Cross Kyoto Daiichi Hospital between January 1st 2008 and December 31st 2017. Data on clinical characteristics and treatment modalities were obtained through the review of medical charts. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The impact of variables on PFS and OS was evaluated by univariate log-rank tests and by multivariate analysis using the Cox proportional hazards model. Results Median age at diagnosis was 78 years old (73-94). The 2-year OS rate was 77.5% (95%Cl: 68.3-84.3%), PFS rate was 77.4% (95%Cl: 68.2-84.3%) in all patients. The 5-year OS rate was 62.3% (95%Cl: 50.2-72.2%), PFS rate was 55.5% (95%Cl: 43.4-66%) in all patients. The average rate of change in body weight after the first therapy was 4.59%. Large changes in body weight ( >9.3%) after the first therapy had worse clinical outcomes with shorter median OS (1.43 years vs. NA, P <0.001 HR 4.39, 95% CI 2.14 to 8.99, see figure 1) and median PFS (1.43 years vs. 6.9 years, P<0.001, HR 3.65, 95%CI 1.82to 7.29, see figure 2). Conclusion Large changes in body weight ( >9.3%) after the first therapy were associated with poor outcomes in elderly people with newly diagnosed aggressive B-cell lymphoma. This suggests that adjusting drug dosage on and after the second therapy in those patients has possible to be improve their survival. Disclosures No relevant conflicts of interest to declare.

Treatment of Aggressive B-Cell Lymphoma in the Elderly: The Influence of SNPs Affecting Pharmacodynamics Is Different Compared to Younger Patient

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1613-1613
Author(s):  
Thomas Melchardt ◽  
Lukas Weiss ◽  
Clemens Hufnagl ◽  
Daniel Neureiter ◽  
Ralf Kemmerling ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
The Elderly ◽  
Tissue Samples ◽  
Younger Patients ◽  
The Impact ◽  
Aggressive B Cell Lymphoma

Abstract Abstract 1613 Background: Elderly patients with aggressive B-cell lymphoma are underrepresented in almost all clinical trials and treatment related toxicity mainly due to anthracycline treatment is a major concern. Individual pharmacogenetic settings may influence the prognosis due to altered efficacy and treatment related toxicity. Several single nucleotide polymorphisms (SNPs) involved in metabolization of chemotherapeutic agents have been proposed to influence the clinical course of disease in younger patients. However, no data are available in elderly patients. Methods: We retrospectively analyzed and characterized 83 consecutively diagnosed patients ≥75 years with aggressive B-cell lymphoma (78 cases of diffuse large B-cell lymphoma and 5 cases of follicular lymphoma grade 3) from January 2004 until December 2011 treated at our tertiary cancer center by chart-based review. DNA was extracted from diagnostic tissue samples and analysis for 10 SNPs with previously reported effect on pharmacodynamics of components of the CHOP regimen were performed with commercially available primers (rs1883112 NCF4, rs3957357 GSTA1, rs4673 CYBA, rs1799977 MLH1, rs1045642 ABCB1, rs9024 CBR1, rs1695 GSTP1, rs17222723 ABCC2, rs7853758 SLC28A3, rs1056892 CBR3). Results: The entire cohort of 83 patients had a median age of 80 years (range 75–97 years) and 43 of 83 patients were male. Based on clinical judgment of fitness 82% of all patients received a combination of anthracycline and rituximab based therapy. The median overall survival (OS) in all patients was 43 months. Unsurprisingly, patients deemed eligible for a treatment with an anthracycline and rituximab had a better median OS than patients not eligible for this approach (54 vs 6 months p< 0.0001). Patients not treated with this combination therapy were significantly older (p<0.0001), had a worse ECOG status (p<0.03) and a higher Charlson index of Comorbidity (CI) (p<0.02). The cohort treated with an anthracycline and rituximab (n=68) had a median age of 79 years and 50% had a CI ≥1. In this group there was no significant difference in the median OS in patients <80 or >80 years of age (54 vs 55 months, Figure A) or with a CI ≤ 1 or CI ≥1 (43 vs 59 months). Tissue samples were available for 97% of these patients, which were used for DNA extraction and SNP analyses. Pharmacogenetic testing of 10 SNPs was performed as described before. The AA genotype of CBR 3 suggesting lower risk for anthracycline related cardiomyopathy or the GG genotype of MLH 1, which influences the mismatch repair system and the promotion of apoptosis e.g. triggered by chemotherapy, was found in 15 of 65 (23%) patients. Patients with either of these genotypes had a better median OS (30 months vs not reached p=0.01, Figure B). In multivariate analysis this benefit remained significant. Additional significant factors were an age-adjusted IPI ≤ 1 and a cumulative dosage of doxorubicin higher than 200mg/m2. The latter is likely a surrogate for overall tolerability of chemotherapy and no early progression. Discussion: Given the encouraging OS data of our unselected cohort we think that elderly patients with aggressive B-cell lymphoma should be offered curative immunochemotherapy with an anthracycline regardless of age taking into account severe comorbidities. We could further show that CBR3 and MLH1 polymorphism had an impact on the OS of these patients. The favorable CBR3 A/A genotype suggests the generation of a lower level of the cardiotoxic compound doxorubicinol after doxorubicin treatment in these patients, who are likely to be more prone to anthracycline-caused toxicity than younger patients. The impact of the MLH1 genotype indeed seems to be changed in elderly compared to younger patients, where the A/A genotype is associated with a better OS in patients treated with R-CHOP. The favorable impact of the G/G phenotype in elderly patients may be caused by a lower susceptibility to apoptosis induction in the healthy tissue. Thus, the meaning of pharmacogenetic markers may be substantially different between the young and the elderly due to the different impact of toxicity and efficacy in these populations. Based on these results a subgroup with exceptionally good OS may be defined for this age. Disclosures: Melchardt: Roche: Honoraria, Speakers Bureau; GSK: Research Funding; Ratiopharm: Research Funding. Weiss:Roche: Honoraria. Greil:Roche: Honoraria, Research Funding, Speakers Bureau; GSK: Research Funding; Ratiopharm: Research Funding. Egle:Roche: Honoraria, Research Funding, Speakers Bureau; GSK: Research Funding; Ratiopharm: Honoraria, Research Funding.

scholarly journals Clinical efficacy and molecular biomarkers in a phase II study of tucidinostat plus R-CHOP in elderly patients with newly diagnosed diffuse large B-cell lymphoma

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Mu-Chen Zhang ◽  
Ying Fang ◽  
Li Wang ◽  
Shu Cheng ◽  
Di Fu ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Molecular Biomarkers ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Abstract Background Elderly patients with diffuse large B-cell lymphoma (DLBCL) present with poor clinical outcome and intolerance to intensive chemotherapy. Histone deacetylase inhibitors (HDACIs) show anti-lymphoma activities and can be applied to treat DLBCL. This study aimed to evaluate efficacy and safety of oral HDACI tucidinostat (formerly known as chidamide) plus R-CHOP (CR-CHOP) in elderly patients with newly diagnosed DLBCL (International Prognostic Index ≥ 2). Results Among 49 patients, the complete response rate was 86%, with overall response rate achieving 94%. The 2-year progression survival (PFS) and overall survival (OS) rates were 68% (95% CI 52–79) and 83% (95% CI 68–91). Comparing with historical control (NCT01852435), the 2-year PFS and OS rates of double-expressor lymphoma phenotype (DEL) were improved, and negative prognostic effect of histone acetyltransferases CREBBP/EP300 mutations was also mitigated by CR-CHOP. Grade 3–4 neutropenia was reported in 171, grade 3–4 thrombocytopenia in 27, and grade 3 anemia in 11 of 283 cycles. No grade 4 non-hematological adverse event was reported. Conclusion CR-CHOP is effective and safe in elderly patients with newly diagnosed DLBCL. Relevance of DEL phenotype and molecular biomarkers on CR-CHOP response warrants further investigation in DLBCL. Trial registration ClinicalTrial.gov, NCT02753647. Registered on April 28, 2016.

scholarly journals Age-dependent increase of treatment-related mortality in older patients with aggressive B cell lymphoma: analysis of outcome, treatment feasibility, and toxicity in 1171 elderly patients with aggressive B cell lymphoma—data from phase II and III trials of the DSHNHL (German High-Grade Non-Hodgkin’s Lymphoma Study Group)

2020 ◽  
Author(s):  
Florian Zettl ◽  
Marita Ziepert ◽  
Bettina Altmann ◽  
Samira Zeynalova ◽  
Gerhard Held ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Patient Population ◽  
Cell Lymphoma ◽  
Age Groups ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Age Dependent ◽  
Aggressive B Cell Lymphoma

AbstractIn elderly patients (pts) with aggressive B cell lymphoma (aNHL), curative treatment often cannot be administered because of comorbidities and tolerability. We analyzed the influence of age in pts > 60 years receiving the R-CHOP-14 regimen within different prospective DSHNHL trials. Of the RICOVER-60 trial and CHOP-R-ESC trials, 1171 aNHL pts were included in this retrospective analysis of age-dependent event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). All patients received prophylactic G-CSF, and anti-infective prophylaxis with amphotericin B mouth wash and oral fluorchinolone was optional. In the CHOP-R-ESC trials, prophylaxis was augmented to include mandatory continuous orally administered aciclovir and a pneumocystis prophylaxis with cotrimoxazole as well as oral fluorchinolones during neutropenia. The patient population was separated into 4 age groups (61–65 years, 66–70 years, 71–75 years, and 76–80 years). The results from the RICOVER-60 trial were subsequently confirmed in the following CHOP-R-ESC trials by a multivariate analysis adjusted for IPI factors and gender. Significant differences (p < 0.001) in EFS, PFS, and OS were seen between age groups (RICOVER-60). Hematotoxicity, infections, and TRM increased with age. TRM was significantly elevated in the age group 76–80 years. Therefore, this analysis shows that an age above 75 years defines an especially vulnerable patient population when being treated with chemoimmunotherapy for aNHL. Prophylactic anti-infective drugs are essential and clinically effective in reducing morbidity when treating elderly aNHL pts.

Role of Radiotherapy to Bulky Disease in Elderly Patients With Aggressive B-Cell Lymphoma

2014 ◽  
Vol 32 (11) ◽  
pp. 1112-1118 ◽  
Author(s):  
Gerhard Held ◽  
Niels Murawski ◽  
Marita Ziepert ◽  
Jochen Fleckenstein ◽  
Viola Pöschel ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prospective Trial ◽  
Multivariable Analysis ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Aggressive B Cell Lymphoma

Purpose R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is standard care for aggressive B-cell lymphoma. A prospective trial was conducted to investigate the role of additive radiotherapy (RT) to bulky and extralymphatic disease. Patients and Methods The best arm of the RICOVER-60 trial (6×R-CHOP–14+2R [R-CHOP administered once every 2 weeks plus two additional applications of rituximab] plus involved-field RT [36 Gy] to sites of initial bulky [≥ 7.5 cm] disease and extralymphatic involvement) was compared with a cohort receiving the same immunochemotherapy but without RT in an amendment to the RICOVER-60 trial (RICOVER-noRTh) in a prospective fashion. Results After a median observation time of 39 months, 164 of 166 RICOVER-noRTh patients were evaluable. In a multivariable analysis of the intention-to-treat population adjusting for International Prognostic Index risk factors and age (> 70 years), event-free survival (EFS) of patients with bulky disease was inferior without additive RT (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.5; P = .005), with trends for inferior progression-free (PFS; HR, 1.8; 95% CI, 1.0 to 3.3; P = .058) and overall survival (OS; HR, 1.6; 95% CI, 0.9 to 3.1; P = .127). In a per-protocol analysis with 11 patients in RICOVER-noRTh excluded for receiving unplanned RT, multivariable analysis revealed HRs of 2.7 (95% CI, 1.3 to 5.9; P = .011) for EFS, 4.4 (95% CI, 1.8 to 10.6; P = .001) for PFS, and 4.3 (95% CI, 1.7 to 11.1; P = .002) for OS for patients not receiving RT to bulky disease. Conclusion Additive RT to bulky sites abrogates bulky disease as a risk factor and improves outcome of elderly patients with aggressive B-cell lymphoma. Whether RT can be spared in patients with (metabolic) complete remission after immunochemotherapy must be addressed in appropriately designed prospective trials.

Prognostic Factors and Treatment Results in Elderly Patients with Aggressive B-Cell Lymphoma: A Geltamo Observational Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1508-1508
Author(s):  
Emilia Pardal ◽  
Eva Diez-Baeza ◽  
Eva González-Barca ◽  
Tomas Garcia-Cerecedo ◽  
Encarna Monzo ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Geriatric Assessment ◽  
Charlson Comorbidity Index ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Malignant Neoplasms ◽  
Comorbidity Index ◽  
Very High ◽  
Aggressive B Cell Lymphoma

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is one of the most common malignant neoplasms in elderly patients, potentially curable when optimum treatment is administered. The combination of rituximab with CHOP chemotherapy (R-CHOP) is considered standard for these patients, but randomized studies published to date are limited to the range of age from 60 to 80 years, so that in patients over this age treatment election is not so clear, usually opting for palliative treatment or a "full" treatment at a reduced dose. This retrospective study is primarily aimed to analyze the influence of the type of treatment and comorbidity scales in overall survival (OS) of a large series of patients >80 years with aggressive B-cell lymphoma. Methods: Eligible patients were aged ≥ 80 years, diagnosed of DLBCL, follicular lymphoma grade 3B or transformed lymphoma. The main patient characteristics were obtained retrospectively from the medical records, including a complete geriatric assessment (CGA, "comprehensive geriatric assessment") and the Charlson comorbidity index. The Ethics Committee of the University Hospital of Salamanca approved the study. Results: 288 patients from 19 GELTAMO hospitals were registered in the study, of which 234 (60% women) were evaluable and have been included in this preliminary analysis. The median age was 84 years (80-94) and the vast majority (94%) were DLBCL. According to the Charlson index, 65% of patients were low-intermediate risk, and according to CGA, 63% of patients were considered "fit". A higher proportion (60% v 44%, p = 0.03) of patients with low or intermediate comorbidity index were treated with a curative intent (CHOP +/- rituximab), as compared with patients with high or very high index. With a median follow up of 41 (range 9-142) months, the median OS was 11.5 months (33% estimated at 3 years). The median OS for patients treated with R-CHOP-like (N=96) was 35.3 months, significantly better (p <0.001) than those achieved with CHOP-like (n=23, 7.9 months), R-CVP (n=20, 6.9 months) or cyclophosphamide- prednisone +/- vincristine (n=69, 6.2 months). Charlson comorbidity index and CGA scale also had a significant influence on OS (median of 14.6 vs. 6.1 months for patients with low or intermediate versus high or very high risk, p = 0.006; and 18 vs 6.6 months for patients "fit" versus "non-fit", p = 0.006). In the multivariate analysis, treatment with R-CHOP-like (RR = 0.4; 95% CI: 0.3-0.6) and IPI <3 (RR = 0.4; 95% CI: 0.3-0.6) had an independent positive influence on OS. Conclusions: In patients over 80 years with DLBCL, treatment with R-CHOP-like was associated with the best results in terms of OS. Therefore, its administration must be considered whenever possible. Disclosures Sancho: CELLTRION, Inc.: Research Funding.

Comparison and modelling of pegylated or unpegylated G-CSF schedules in CHOP-14 regimen of elderly patients with aggressive B-cell lymphoma

2013 ◽  
Vol 92 (12) ◽  
pp. 1641-1652 ◽  
Author(s):  
S. Zeynalova ◽  
◽  
M. Ziepert ◽  
M. Scholz ◽  
S. Schirm ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Aggressive B Cell Lymphoma

scholarly journals Management Strategies for Elderly Patients with Diffuse Large B-Cell Lymphoma

2012 ◽  
Vol 08 (02) ◽  
pp. 123 ◽  
Author(s):  
Loretta J Nastoupil ◽  
Rajni Sinha ◽  
Christopher R Flowers ◽  
◽  
◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Future Research ◽  
Ageing Population ◽  
Prognostic Features ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of lymphoma and most commonly presents in the sixth decade. Given the dramatic rise of the incidence of lymphoma since the late 1990s in patients who present over the age of 65, and the expected increase in the prevalence of DLBCL with the ageing population, defining appropriately tailored modern therapy for elderly DLBCL patients is an increasingly important clinical concern. Moreover, age has been one of the most important adverse prognostic features, with numerous studies associating older age with inferior outcomes. Although it has been well established that B-cell diversity decreases with age, and that the loss of diversity can be associated with clonal expansion of B-cells, it remains unknown how this or other factors contribute to the pathogenesis and poor prognosis in elderly patients with DLBCL. Furthermore, elderly patients often have more co-morbid illnesses, worse performance status, less haematologic reserve and altered pharmacokinetics related to decreased metabolism and clearance of drugs. We examine the impact of these factors on therapeutic decision-making in patients with DLBCL and explore treatment alternatives for elderly individuals. Future research is needed not only to address treatment strategies but also to define the biologic heterogeneity between younger and older patients with DLBCL, so that more rational therapeutic approaches can be investigated.

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