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 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.

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.

Aggressive Chemotherapy (CHOEP-14) and Rituximab or High-Dose Therapy (MegaCHOEP) and Rituximab for Young, High-Risk Patients with Aggressive B-Cell Lymphoma: Results of the MegaCHOEP Trial of the German High — Grade Non-Hodgkin Lymphoma Study Group (DSHNHL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 404-404 ◽  
Author(s):  
Norbert Schmitz ◽  
Maike Nickelsen ◽  
Marita Ziepert ◽  
Matthias Haenel ◽  
Peter Borchmann ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Conventional Chemotherapy ◽  
High Risk Patients ◽  
Risk Patients ◽  
Aggressive B Cell Lymphoma

Abstract Abstract 404 Comparison of conventional chemotherapy with high-dose therapy followed by autologous stem cell transplantation (HDT/ASCT) administered to young, high-risk patients with aggressive B-cell lymphoma as part of first-line therapy gave conflicting results; none of the randomized studies used rituximab (R) in combination with conventional or HDT. In March 2003 we started a randomized phase III study for young (18-60 years), high-risk (age-adjusted IPI 2 or 3) patients with aggressive lymphoma. For patients with B-cell lymphomas this study compared 8 cycles of CHOEP-14 (CHOP + etoposide 300 mg/m2 given every 2 weeks) with MegaCHOEP. The MegaCHOEP program used cyclophoshamide (1500 mg/m2 in cycle 1; 4500 mg/m2 in cycles 2 and 3; 6000 mg/m2 in cycle 4), doxorubicin (70 mg/m2 in all cycles), vincristine (2 mg, all cycles), etoposide (600 mg/m2 , cycle 1; 960 mg/m2 , cycles 2 and 3; 1480 mg/m2, cycle 4), and prednisone (500 mg, all cycles) to be administered every 21 days. Hematopoietic stem cells were harvested after cycles 1 and 2 and reinfused after HDT cycles 2, 3, and 4. Feasibility, safety, and efficacy of MegaCHOEP + / - R have been described (Glass et al. Blood 2006 and BMT 2006). The phase III study originally had four arms (8 × CHOEP – 14, 8 × CHOEP – 14 and 6 × R, MegaCHOEP, and MegaCHOEP and 6 × R). Treatment arms without R were closed in June 2004 because other studies (e.g the MInT study) had shown major improvement in outcome parameters when R was added to chemotherapy. The study continued comparing 8 × CHOEP – 14 and 6 × R (375 mg/m2) with MegaCHOEP and 6 × R (375 mg/m2). At the time of this analysis 346 patients (pts) had been recruited; 216 pts. (median age 48 years, LDH > N 97 %, stage III or IV 96%, ECOG > 1 35%) had been randomized until 07 / 07 and were availabel for this planned interim analysis ( 8 × CHOEP – 14 + 6 × R, n = 91; MegaCHOEP + 6 × R, n = 94; 8 × CHOEP – 14, n = 15; MegaCHOEP, n = 16). Major toxicities included mucositis, diarrhea, and infections all of which were significantly more frequent in the MegaCHOEP arm of the study. Treatment – related deaths occurred in 5 / 94 pts. ( 5.3%) in the MegaCHOEP arm and in 1 / 91 pts. (1.1 %) in the R – CHOEP arm (p = 0.211). Surprisingly, the 3 – year event – free survival ( EFS : time from randomization to either disease progression, no CR / CRu at the end of treatment, initiation of salvage therapy, relapse or death from any cause) was better after conventional than after HDT / ASCT: 71.0% after 8 × CHOEP-14 + 6 × R vs. 56.7 % after MegaCHOEP + 6 × R (p = 0.050). After a median observation time of 29 months the estimated 3-year overall survival was 83.8 % after 8 × CHOEP – 14 + 6 × R and 75.3 % after MegaCHOEP + 6 × R (p = 0.142). Progression – free survival was 76.0 % after 8 × CHOEP – 14 + 6 × R and 64.6 % after MegaCHOEP + 6 × R (p = 0.119). A comparison of the rituximab-containing treatment arms (8 × CHOEP 14 + 6 × R and Mega CHOEP + 6 × R) with the chemotherapy – only arms (8 × CHOEP -14 and MegaCHOEP) revealed a 27.1 % difference in the 3-year EFS-rate ( p = 0.003 ) pointing to the unexpectedly high efficacy of R particularly in untreated, young, high-risk patients with aggressive B-NHL. These data were presented to the members of the study group and the data safety and monitoring committee who decided to stop the MegaCHOEP arm of the study. In conclusion, 8 × CHOEP -14 + 6 × R gave excellent results in young, high-risk patients with untreated aggressive B cell lymphoma. The 3-year EFS and OS are the best ever reported for this group of patients. MegaCHOEP + 6 × R was no better than aggressive conventional chemotherapy regarding any of the study endpoints; EFS (primary endpoint of the study) was significantly worse. Because of higher toxicity and inferior survival the MegaCHOEP arm was discontinued. HDT / ASCT has no role to play as part of first-line therapy for patients with high-risk aggressive B cell lymphoma if rituximab is combined with aggressive conventional chemotherapy. Disclosures: Schmitz: Roche: Honoraria, Research Funding. Nickelsen:Roche: Honoraria. Trümper:Roche: Honoraria, Research Funding. Pfreundschuh:Roche: Consultancy, Honoraria, Research Funding. Glass:Roche: Honoraria, Research Funding.

Outcome of Elderly Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: Subgroup Analysis from the UK NCRI R-CHOP 14 Vs 21 Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1516-1516
Author(s):  
Andrea Kühnl ◽  
David Cunningham ◽  
Nicholas Counsell ◽  
Eliza A Hawkes ◽  
Wendi Qian ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
The Uk ◽  
Large B Cell ◽  
Grade Iii

Abstract Background: Elderly patients with diffuse large B-cell lymphoma (DLBCL) have an inferior prognosis compared to younger patients. Dose intense administration of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP14) is superior to 3-weekly CHOP in elderly DLBCL patients (Pfreundschuh, Blood 2004), but this benefit has not been demonstrated with addition of rituximab (Delarue, Lancet Oncol 2013). We have previously shown that R-CHOP14 did not improve outcome compared to standard R-CHOP21 in newly diagnosed DLBCL patients aged 19-88 years across all subgroups (Cunningham, Lancet 2013). Here, we provide a detailed subgroup analysis of elderly patients (over 60 years) from the UK NCRI R-CHOP14 vs 21 randomised phase 3 trial. Methods: Between 2005 and 2008, 1080 patients were randomly assigned to receive 8 cycles R-CHOP21 or 6 cycles R-CHOP14 (+ G-CSF) with two additional rituximab applications. Of these, 604 patients were over 60 years and included in the current analysis (301 in the R-CHOP21 arm, 303 in the R-CHOP14 arm), with a median follow-up of 45 months. Results: Baseline characteristics were well balanced between treatment arms. 36% of patients were over 70 years, 15% had a WHO performance status (PS) of 2, 65% stage III/IV disease, 44% bulky disease and 42% B symptoms. There was a trend towards a higher rate of BCL6 rearrangements (26% vs. 16%; P=0.10) and concurrent MYC - and BCL2 rearrangements (double hit lymphoma as determined by FISH, 8% vs. 2%; P=0.06) in the R-CHOP14 arm compared to the R-CHOP21 arm. 85% (257/303) of patients received 8 cycles of R-CHOP14, whereas only 76% (230/301) completed all 8 cycles R-CHOP21. However, percentage of patients receiving at least 6 cycles of therapy was similar (88% and 89%, respectively). Dose delays of myelosuppressive drugs occurred more frequently in patients receiving R-CHOP21 vs. R-CHOP14 (51% vs. 39%; P=0.03) due to a higher incidence of haematological toxicities likely related to the reduced use of G-CSF. G-CSF was mandatory for patients on R-CHOP14 and was given to 57% of patients on R-CHOP21 as secondary prophylaxis. The frequency of dose reductions was similar in the R-CHOP21 and R-CHOP14 arms (15% vs. 16%; P=0.73). Toxicities of grade III+ were seen in 72% and 60% of patients in the R-CHOP14 and R-CHOP21 arms, respectively. There was evidence of a higher incidence of grade III+ neutropenia (62% vs. 36%) and a lower rate of thrombocytopenia (7% vs. 12%) in the R-CHOP21 arm compared to R-CHOP14. The incidence of fever and infections was similar in both arms. There was no evidence of a difference in response rates between the R-CHOP14 and R-CHOP21 arms [complete response (CR)/unconfirmed CR (CRu) rates: 62% vs. 67%, respectively; overall response rate both 91%]. CR/CRu rates after 4 cycles of therapy were 33% and 39% respectively (P=0.15). There was no difference regarding progression-free survival (PFS) and overall survival (OS) between arms, neither in the total cohort of elderly patients, nor in the subgroup of patients over 70 years [OS (all elderly): hazard ratio (HR) 0.91 (95% CI: 0.67-1.24); P=0.55; PFS (all elderly): HR 0.98 (95% CI: 0.74-1.29); P=0.86]. 3-year PFS was 71% (95% CI: 67-74) in all patients over 60 years and 64% (95% CI: 58-71) in patients over 70 years. 3-year OS was 75% (95% CI: 72-79) and 67% (95% CI: 61-74) in patients over 60 years and over 70 years, respectively. In multivariate analysis including individual factors of the International Prognostic Index (IPI), as well as age as continuous variable, gender, presence of B symptoms, bulky disease, b2-microglobulin higher than 3mg/l and albumin higher than 35 g/l, only age was of independent prognostic significance for OS (P=0.01). Besides the standard IPI and the NCCN-IPI, an elderly IPI (E-IPI; Advani, BJH 2010) and the ABE4 score (Prochazka, PLoS One 2014) have been proposed for better prognostication of elderly DLBCL patients. A detailed comparison of these different prognostic models in our dataset will be presented at the meeting. Conclusion: Outcome and toxicities in DLBCL patients over 60 years treated within the NCRI R-CHOP14 vs 21 trial are comparable to results from other randomised studies investigating R-CHOP14 or R-CHOP21 in elderly DLBCL patients. Our data further support the similar efficacy and tolerability of both R-CHOP variants for first-line treatment of this patient group. Disclosures Cunningham: Amgen: Research Funding; Medimmune: Research Funding; Astra Zeneca: Research Funding; Bayer HealthCare Pharmaceuticals: Research Funding; Merrimack: Research Funding; Merck Serono: Research Funding; Celgene: Research Funding; Sanofi: Research Funding. Pocock:Janssen: Honoraria. Ardeshna:Roche: Honoraria.

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 Good Outcome after R-Hyper-CVAD/R-MA in High-Risk Aggressive B-Cell Lymphoma: A Single-Center Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4587-4587
Author(s):  
Kristina Sonnevi ◽  
Maria Ljungqvist ◽  
Joel K Joelsson ◽  
Sara Harrysson ◽  
Tove Wästerlid ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Single Center ◽  
Good Outcome ◽  
High Risk Disease ◽  
Extranodal Disease ◽  
Aggressive B Cell Lymphoma

Abstract INTRODUCTION Patients with high-risk aggressive B-cell lymphoma exhibit poor survival after R-CHOP-like immunochemotherapy. More intensive regimens yield higher rates of remission but also of complication, which have hindered their use, particularly in older patients. At Karolinska, the standard intensive regimen has been R-Hyper-CVAD/R-MA for patients with high-risk characteristics, such as high age-adjusted international prognostic index (aaIPI) and extranodal disease. METHODS In this analysis, high-risk disease was defined as aaIPI ≥ 2 or any extranodal involvement. We examined Karolinska's 136 patients who received at least one cycle of R-Hyper-CVAD/R-MA in first-line therapy for high-risk disease, excluding Burkitt, transformed, and primary CNS lymphoma. Patients were diagnosed between 2006 and 2020; 89 were diffuse large B-cell lymphoma, 23 high-grade B-cell lymphoma, 17 primary mediastinal B-cell lymphoma, 4 T cell/histiocyte-rich B-cell lymphoma, 2 aggressive B-cell lymphoma unspecified, 1 lymphomatoid granulomatosis grade 3. For outcome, we investigated progression-free survival (PFS). RESULTS In this cohort of 136 patients with high-risk disease treated with at least one cycle of R-Hyper-CVAD/R-MA, the median age was 52 years (range, 19-69); 36 patients (26%) were 61-69 years old. Lactate dehydrogenase was elevated in 92%, stage III-IV disease was seen in 93%, WHO performance status ≥2 in 49%, aaIPI = 3 in 38%, extranodal disease in 30%, CNS involvement in 17%, and Charlson comorbidity index ≥2 in 11%. At 5 years, the PFS in all patients was 72% and in the 50 patients with aaIPI = 3, 66% (Figure 1). In patients ≤60 years old, 5-year PFS was 76% (aaIPI = 3, 69%). In patients 61-69 years, the 5-year PFS was 58% (aaIPI = 3, 59%). Six out of 136 patients (4%) died from toxicity during induction therapy (3/6 were 61-69 years old). CONCLUSIONS This is to our knowledge the largest published single-center series of patients treated with R-Hyper-CVAD/R-MA for high-risk aggressive B-cell lymphoma. Outcome in these patients aged 19-69 years was excellent, with 5-year PFS 72%. Particularly patients with aaIPI = 3 showed rather good outcome with 5-year PFS 66%. For comparison, in Sweden the 5-year overall survival of R-CHOP-treated patients ≤60 years with aaIPI = 3 is 40% (Melén CM et al. Brit J Haematol. 614-622. 2016). We will continue to explore R-Hyper-CVAD/R-MA as primary therapy for high-risk aggressive B-cell lymphoma. Figure 1 Figure 1. Disclosures Wahlin: Gilead Sciences: Research Funding; Roche: Consultancy, Research Funding.

scholarly journals Adding Etoposide to R-CHOP (R-CHOEP) Does Not Significantly Increase the Risk of Secondary Neoplasms in Patients with Aggressive B-Cell Lymphoma - Results from Randomized Phase 3 Trials of the German Lymphoma Alliance (GLA)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-6
Author(s):  
Fabian Frontzek ◽  
Marita Ziepert ◽  
Maike Nickelsen ◽  
Bettina Altmann ◽  
Bertram Glass ◽  
...  
Keyword(s):  
B Cell ◽  
Solid Tumors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Board ◽  
First Line ◽  
Phase 3 ◽  
Increased Risk ◽  
Aggressive B Cell Lymphoma

Introduction:Considering the increasing numbers of lymphoma patients (pts) surviving long-term, late effects of current treatment strategies such as secondary (sec) malignancies gain increasing importance. Many treatment regimens used in pts with lymphoma (R-CHOEP, DA-EPOCH-R, BEACOPP) include etoposide, a cytotoxic agent reported to increase sec leukemias. In order to further investigate the role of etoposide in inducing sec malignancies in pts with aggressive lymphoma we analyzed the R-MegaCHOEP trial (Schmitz et al., Lancet Oncology 2012) where young, high-risk pts with aggressive B-cell lymphomas had received R-CHOEP or R-MegaCHOEP, a regimen containing very high doses of etoposide (4g/m2). We compared rates of secondary tumors to incidences found in young patients treated with R-CHOP only. Methods:We analyzed 1536 pts aged 18-60 years with aggressive B-cell lymphoma treated in the prospective phase 3 trials FLYER (NCT00278421; n=588, median observation time (OT)=66 months), UNFOLDER (NCT00278408; n=695, median OT=72 months) and MegaCHOEP (NCT00129090; n=253, median OT=112 months) to compare the cumulative incidences of sec neoplasms. We performed a competing risk analysis for time from randomization to occurrence of sec malignancy (myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or other) according to first-line therapy with R-CHOP (n=1283) vs. R-CHOEP (n=127) vs. R-MegaCHOEP (n=126). We used a cause-specific hazard model adjusted for gender, age (&gt;50 vs. &lt;= 50 years) and radiotherapy. Results:Adjusting for competing events, we found sec MDS/AML in 0.3% of pts treated with R-CHOP, in 1% of pts treated with R-CHOEP and in 2% of pts following treatment with R-MegaCHOEP. Cause-specific hazard ratios showed a trend for increased risk for sec AML following R-MegaCHOEP in comparison to R-CHOP (HR 5.2, 95%CI (1.0; 27.5), p=0.052) while R-CHOEP did not significantly increase the incidence of sec AML (HR 1.4, 95%CI (0.1; 14.0), p=0.777). Male gender and age &gt;50 years showed a trend for increasing sec AML. We found very similar incidences of sec solid tumors (not MDS/AML) affecting 4% of pts treated with R-CHOP or R-MegaCHOEP and 6% of pts following R-CHOEP regimen. The only factor significantly increasing the risk of sec solid tumors was age &gt;50 years (HR 2.6, 95%CI (1.5; 4.3), p&lt;0.001). Conclusions:This analysis shows that sec malignancies represent rare events in younger patients with aggressive B-cell lymphoma, even after extreme dose-escalation of etoposide. Compared to standard R-CHOP, 8 cycles of R-CHOEP were not associated with increased risk of sec AML or solid tumors thus remaining an attractive first-line treatment for young high-risk pts with DLBCL. Disclosures Haenel: Amgen, Novartis, Roche, Celgene, Takeda, Bayer:Honoraria.Truemper:Janssen:Consultancy;Mundipharma:Research Funding;Nordic Nanovector:Consultancy;Roche:Research Funding;Seattle Genetics:Research Funding;Takeda Europe:Consultancy, Research Funding.Held:MSD:Consultancy;Acrotech, Spectrum:Research Funding;Amgen:Research Funding;BMS:Consultancy, Other: Travel Grants, Research Funding;Roche:Consultancy, Other: travel grants, Research Funding.Borchmann:Bristol Myers Squibb:Research Funding;Takeda:Research Funding.Dreyling:Celgene:Consultancy, Research Funding, Speakers Bureau;Roche:Consultancy, Research Funding, Speakers Bureau;Beigene:Consultancy;Janssen:Consultancy, Research Funding, Speakers Bureau;Novartis:Consultancy;Abbvie:Research Funding;Astra Zeneca:Consultancy;Bayer:Consultancy, Speakers Bureau;Gilead:Consultancy, Research Funding, Speakers Bureau.Viardot:Roche:Honoraria, Other: advisory board;Kite/Gilead:Honoraria, Other: advisory board;Novartis:Honoraria, Other: advisory board;Amgen:Honoraria, Other: advisory board.Kroschinsky:Riemsser:Research Funding;Roche:Consultancy, Honoraria, Other: Support of parent study and funding of editorial support;Gilead:Consultancy;BMS/Celgene:Consultancy, Honoraria;Sandoz:Research Funding.Ott:NIH:Consultancy, Other: Co-inventor on a patent related to the MCL35 assay filed at the National Institutes of Health, United States of America..Lenz:Bayer:Consultancy, Honoraria, Research Funding, Speakers Bureau;Janssen:Consultancy, Honoraria, Research Funding, Speakers Bureau;Novartis:Consultancy;Gilead:Consultancy, Honoraria, Research Funding, Speakers Bureau;AQUINOX:Research Funding;AstraZeneca:Consultancy, Honoraria, Research Funding;Celgene:Consultancy, Honoraria, Speakers Bureau;Verastem:Research Funding;Morphosys:Consultancy, Honoraria, Research Funding;Roche:Consultancy, Honoraria, Research Funding, Speakers Bureau;Agios:Research Funding;BMS:Consultancy.Schmitz:Riemser:Honoraria;Takeda:Honoraria;Janssen:Research Funding;Bristol-Myers Squibb:Current equity holder in publicly-traded company.

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