Therapy with Imatinib In Elderly CML Patients (>65years): Results of the German CML-Study IV.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3411-3411
Author(s):  
Susanne Saussele ◽  
Nadine Pletsch ◽  
Michael Lauseker ◽  
Armin Leitner ◽  
Susanne Jung-Munkwitz ◽  
...  

Abstract Abstract 3411 Background: Dose of therapy and time to response may be different in the elderly as compared to younger patients with CML. This has been reported previously for interferon α (Berger et al., Leukemia 2003). For imatinib, contradictory results have been presented (Rosti et al. Haematologica 2007, Guliotta et al. Blood 2009). Aims: An analysis comparing dose-response relationship in patients more or less than 65 years (y) of age is warranted. Methods: We analysed the German CML-Study IV, a randomized 5-arm trial to optimize imatinib therapy by combination, dose escalation and transplantation. Patients older and younger than 65y randomized to imatinib 400 mg (IM400) or 800 mg (IM800) were compared with regard to time to hematologic, cytogenetic and molecular remissions, imatinib dose, adverse events (AEs) and overall survival (OS). Results: From July 2002 to April 2009, 1311 patients with Ph+ CML in chronic phase were randomized, 623 patients were evaluable, 311 patients for treatment with IM400 and 312 for IM800. 84 (27%) and 66 (21%), respectively, were older than 65 years. All patients were evaluable for hematologic, 578 (140 >65y and 438 <65y) for cytogenetic, and 600 (143 and 457, respectively) for molecular responses. Median age was 70y vs. 49y for IM400 and 69y vs. 46y for IM800. The median dose per day was lower for elderly patients with IM800 (517mg vs. 666mg) and the same with IM400 (400mg each). Patients' characteristics at baseline were evenly distributed in all groups regarding gender, follow-up, hemoglobin, platelet count and spleen size. Leukocyte counts were significantly lower in elderly patients (IM400: 50/nl vs. 78/nl, IM800: 36/nl vs. 94/nl). EURO score was different due to age in elderly patients (low risk: IM400: 11% vs. 43%, IM800: 14% vs. 42%; intermediate risk: IM400: 79% vs. 44% and IM800: 73% and 43%). There was no difference in cytogenetic and molecular analyses between treatment groups. With regard to efficacy, there was no difference for older patients in achieving a complete cytogenetic remission (CCR) and major molecular remission (MMR) if IM400 and IM800 were compared together. If treatment groups were analyzed separately, older patients treated with IM400 reached CCR and MMR statistically significant slower than younger patients (CCR: median 14.2 months vs. 12.1 months, p=0.019; MMR: median 18.7 months vs. 17.5 months, p=0.006). There was no difference with IM800 (CCR: median 7.7 months vs. 8.9 months, MMR: median 9.9 months vs. 10.0 months). 3y-OS for older patients >65y was 94.7% and for patients <65y was 96.1%. Some differences were observed in the safety analyses. 530 patients (IM400: 278, IM800: 252) were evaluated on common toxicity criteria (WHO). Some hematologic AEs were documented slightly more often in the elderly than in the younger patients: for IM400 anemia grade 1–2 (60 vs. 42%) and leukopenia grade 3–4 (5.6 vs. 1.4%) and for IM800 anemia grade 1–4 (64 vs.47% and 7.2 vs. 5.7%) and thrombocytopenia grade 3–4 (9.3 vs. 7.1%). Non hematologic AEs were more prominent in IM800 and were mainly gastrointestinal symptoms (IM400: 33 vs. 31%, IM800: 48 and 44%) and edema (IM400: 28 vs. 29%, IM800: 35 vs. 50%). There was no difference for grade 3/4 non-hematological AEs in older patients in both groups. Conclusions: Imatinib 400 mg and 800 mg are well tolerated also in the elderly. The IM800 dosage was more tolerability-adapted for the elderly, but there was no difference in reaching a CCR and MMR in contrast to the IM400 where a significantly slower response was detected in the elderly. Whether this difference is clinically relevant has yet to be determined. Updated results will be presented. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Employment, Equity Ownership, Research Funding. German CML-Study Group:Deutsche Krebshilfe: Research Funding; Novartis: Research Funding; Roche: Research Funding; BMBF: Research Funding; Essex: Research Funding.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 96-96 ◽  
Author(s):  
Ulrike Proetel ◽  
Nadine Pletsch ◽  
Michael Lauseker ◽  
Lida Kalmanti ◽  
Annette Schreiber ◽  
...  

Abstract Introduction The outcome of elderly patients with chronic myeloid leukemia (CML) treated with imatinib has been studied in several trials. However, there are no reports on the effects of different imatinib dosages in older vs. younger CML patients. Methods To evaluate the efficacy of imatinib in the elderly, we analyzed data from the German CML-Study IV, a randomized 5-arm trial designed to optimize imatinib therapy alone or in combination. There was no upper age limit for inclusion. Patients with BCR-ABL positive CML in chronic phase randomized to imatinib 400 mg/d (IM400) or imatinib 800 mg/d (IM800) were compared, stratified according to median age at diagnosis in western populations ≥ 65 years vs. < 65 years, regarding effectively administered imatinib dose, time to hematologic, cytogenetic and molecular remissions, adverse events (AEs), rates of progression to accelerated phase (AP) and blast crisis (BC), survival, and causes of death. The full 800 mg dose was given after a 6 weeks run-in period with imatinib 400 mg/d to avoid excessive cytopenias. The dose could then be reduced according to tolerability for maximum patients' compliance. Results From July 2002 through March 2012, 1,551 patients were randomized, 828 of these to IM400 or IM800. Median age of these patients was 52 years (IM400: 53 years; IM800: 51 years). 784 patients were evaluable for follow-up (IM400: 382; IM800: 402). 193 patients were ≥ 65 years, 591 < 65 years. 110 patients (29%) on IM400 and 83 (21%) on IM800 were ≥ 65 years. Median observation time on IM400 was 63.0 months in the elderly and 67.6 months in the younger group, on IM800 50.9 months in the elderly and 50.1 months in the younger group. The median dose per day was lower for elderly patients on IM800 (421 mg/d for patients ≥ 65 years vs. 556 mg/d for patients < 65 years), with the highest median dose in the first year (466mg/d for patients ≥ 65 years vs. 630mg/d for patients < 65 years). The median dose for patients on IM400 was 400 mg/d for both age groups. There was no difference between age groups in achieving a complete hematologic remission or a complete cytogenetic remission, neither if IM400 and IM800 were combined, nor in an analysis according to treatment groups. Elderly patients on IM400 achieved major molecular remission (MMR) and deep molecular remission (MR4) significantly later than younger patients (18.1 vs. 15.9 months, p=0.013; 54.4 vs. 33.3 months, p=0.012, respectively) whereas no difference was detected for patients on IM800 (11.9 vs. 10.5 months; 24.2 vs. 26.1 months, respectively). Imatinib was well tolerated in elderly patients with only few WHO grade 3-4 AEs being more frequent in the elderly than in younger patients (dermatologic AEs on IM400: 5.4 vs. 0.4%; infections on IM800: 8.3 vs. 2.5%). There were no significant differences between age groups in probabilities of progression to AP or BC neither if IM400 and IM800 were combined, nor in an analysis according to treatment groups. Five-year age-adjusted relative survival for elderly patients was comparable to that of younger patients. Conclusion We could demonstrate that elderly patients achieved molecular remissions significantly later when treated with standard dose imatinib but not when treated with higher imatinib dosages. As the safety profile of IM800 in senior patients was favorable too we conclude, that the optimal dose for elderly patients could be higher than 400 mg/d. Disclosures: Müller: Ariad: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Hochhaus:Pfizer: Consultancy; ARIAD: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Travel Other. Hehlmann:BMS: Consultancy, Research Funding; Novartis: Research Funding. Saussele:BMS: Honoraria, Research Funding, Travel, Travel Other; Pfizer: Honoraria; Novartis: Honoraria, Research Funding, Travel Other.



2019 ◽  
Vol 72 (8) ◽  
pp. 1466-1472
Author(s):  
Grażyna Kobus ◽  
Jolanta Małyszko ◽  
Hanna Bachórzewska-Gajewska

Introduction: In the elderly, impairment of kidney function occurs. Renal diseases overlap with anatomic and functional changes related to age-related involutionary processes. Mortality among patients with acute renal injury is approximately 50%, despite advances in treatment and diagnosis of AKI. The aim: To assess the incidence of acute kidney injury in elderly patients and to analyze the causes of acute renal failure depending on age. Materials and methods: A retrospective analysis included medical documentation of patients hospitalized in the Nephrology Clinic during the 6-month period. During this period 452 patients were hospitalized in the clinic. A group of 77 patients with acute renal failure as a reason for hospitalization was included in the study. Results: The prerenal form was the most common cause of AKI in both age groups. In both age groups, the most common cause was dehydration; in the group of patients up to 65 years of age, dehydration was 29.17%; in the group of people over 65 years - 43.39%. Renal replacement therapy in patients with AKI was used in 14.29% of patients. In the group of patients up to 65 years of age hemodialysis was 16.67% and above 65 years of age. -13.21% of patients. The average creatinine level in the group of younger patients at admission was 5.16 ± 3.71 mg / dl, in the group of older patients 3.14 ± 1.63 mg / dl. The size of glomerular filtration GFR in the group of younger patients at admission was 21.14 ± 19.54 ml / min, in the group of older patients 23.34 ± 13.33 ml / min. Conclusions: The main cause of acute kidney injury regardless of the age group was dehydration. Due to the high percentage of AKI in the elderly, this group requires more preventive action, not only in the hospital but also at home.



2011 ◽  
Vol 5 ◽  
pp. CMO.S6983 ◽  
Author(s):  
Joleen M. Hubbard ◽  
Axel Grothey ◽  
Daniel J. Sargent

The majority of patients with gastrointestinal cancers are over the age of 65. This age group comprises the minority of the patients enrolled in clinical trials, and it is unknown whether older patients achieve similar results as younger patients in terms of survival benefit and tolerability. In addition, there are few studies specifically designed for patients over 65 years. Subset analyses of individual trials and studies using pooled patient data from multiple trials provide some understanding on outcomes in older patients with gastrointestinal cancers. This article reviews the evidence on chemotherapeutic regimens in the elderly with colorectal, pancreatic, and gastroesophageal cancers, and discusses a practical approach to provide the best outcomes for older patients.



2017 ◽  
Vol 126 (4) ◽  
pp. 1201-1211 ◽  
Author(s):  
Benjamin Brokinkel ◽  
Markus Holling ◽  
Dorothee Cäcilia Spille ◽  
Katharina Heß ◽  
Cristina Sauerland ◽  
...  

OBJECTIVE The purpose of this study was to compare long-term prognosis after meningioma surgery in elderly and younger patients as well as to compare survival of elderly patients with surgically treated meningioma to survival rates for the general population. METHODS Five hundred meningioma patients (median follow-up 90 months) who underwent surgery between 1994 and 2009 were subdivided into “elderly” (age ≥ 65 years, n = 162) and “younger” (age < 65 years, n = 338) groups for uni- and multivariate analyses. Mortality was compared with rates for the age- and sex-matched general population. RESULTS The median age at diagnosis was 71 in the elderly group and 51 years in the younger group. Sex, intracranial tumor location, grade of resection, radiotherapy, and histopathological subtypes were similar in the 2 groups. High-grade (WHO Grades II and III) and spinal tumors were more common in older patients than in younger patients (15% vs 8%, p = 0.017, and 12% vs 4%, p = 0.001, respectively). The progression-free interval (PFI) was similar in the 2 groups, whereas mortality at 3 months after surgery was higher and median overall survival (OS) was shorter in older patients (7%, 191 months) than in younger patients (1%, median not reached; HR 4.9, 95% CI 2.75–8.74; p < 0.001). Otherwise, the median OS in elderly patients did not differ from the anticipated general life expectancy (HR 1.03, 95% CI 0.70–1.50; p = 0.886). Within the older patient group, PFI was lower in patients with high-grade meningiomas (HR 24.74, 95% CI 4.23–144.66; p < 0.001) and after subtotal resection (HR 10.57, 95% CI 2.23–50.05; p = 0.003). Although extent of resection was independent of perioperative mortality, the median OS was longer after gross-total resection than after subtotal resection (HR 2.7, 95% CI 1.09–6.69; p = 0.032). CONCLUSIONS Elderly patients with surgically treated meningioma do not suffer from impaired survival compared with the age-matched general population, and their PFI is similar to that of younger meningioma patients. These data help mitigate fears concerning surgical treatment of elderly patients in an aging society.



Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1029-1029
Author(s):  
Jeffrey E Lancet ◽  
Rami S. Komrokji ◽  
HuiYi Lin ◽  
Carlos M. de Castro ◽  
David A. Rizzieri ◽  
...  

Abstract Abstract 1029 Poster Board I-51 Background: Elderly patients with AML have a poor outcome, with low complete response (CR) rates and durations of CR that are typically less than 1 year, highlighting the need for more effective post-remission therapy. 5-azacitidine (AZA) is a nucleoside analogue/DNA methyltransferase inhibitor approved for use in all FAB subtypes and risk categories of myelodysplastic syndromes (MDS). In higher-risk patients with MDS, including those with AML (former RAEB-T subtype), AZA improves overall survival and delays the time to leukemia transformation. We undertook a phase 2 pilot study of low-dose subcutaneous (SC) AZA in older adult patients with AML in 1st CR or CR with incomplete platelet recovery (CRp) following standard induction therapy. Methods: Study objectives included the following: 1) determine the one year disease-free survival in elderly patients with acute myeloid leukemia (AML) in first CR/ CRp treated with low-dose SC AZA as post-remission therapy. 2) determine safety and tolerability of SC AZA administered in the post-remission setting. 3) investigate the relationship between bone marrow genomic promoter methylation with 1-year disease-free survival. Eligibility included age ≥ 60 with AML in 1st CR/ CRp following 1-2 cycles of induction chemotherapy and 1-2 cycles of consolidation therapy, ECOG PS 0-2, adequate end-organ function. AZA was administered subcutaneously on 1 of 2 different dosing schedules: A) 50 mg/m2/d x 5d (d 1-5), or B) 50 mg/m2/d x 7d (d 1-5, 8-9). Cycles were repeated every 4 weeks, and up to 12 cycles. Results: As of August 2009, 16 patients have been enrolled on the study and 15 are currently evaluable. Nine patients received dosing schedule A and 6 received schedule B. Median age was 69 years (range 62-81); M/F was 13/2; baseline cytogenetic risk categories at initial diagnoses: poor (6), intermediate (8), and unknown/not done (1). Two of 15 patients had a history of antecedent MDS. Nine of 15 patients (60%) required 2 cycles of induction chemotherapy to achieve CR/CRp. The median time from achievement of CR/CRp to AZA initiation was 13.6 weeks (range 7 – 21.9 weeks). To date, the median number of AZA cycles received was 4, ;5 patients have received ≥ 6 cycles, 2 of whom have received the 12 planned cycles and another who remains on-study after 11 cycles. Median duration of CR/CRp was 54.8 weeks (95% CI: 28.1-96.4 weeks) estimated using the Kaplan-Meier method. Only 2 of 15 (13%) patients developed grade 3-4 non-hematologic adverse events (colitis, headache). Six of 15 (40%) patients developed reversible grade 3-4 neutropenia or thrombocytopenia, but only 3 required dose reduction. No patients discontinued AZA due to toxicity, and there were no deaths that occurred on-study. Criteria for early stoppage, based upon toxicity, have not been reached. Methylation array analyses are ongoing. SC AZA administered as maintenance therapy in older patients with AML in 1st CR/CRp appears feasible and safe. Extended treatment was possible in a high proportion of patients, with encouraging early signs of durable remissions. Accrual to this trial is ongoing and updated results will be presented. Disclosures: Lancet: Celgene: Research Funding. Komrokji:Celgene: Research Funding, Speakers Bureau. de Castro:Celgene: Speakers Bureau. Rizzieri:Celgene: Research Funding, Speakers Bureau. List:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.



Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4152-4152
Author(s):  
Chadi Nabhan ◽  
Michelle Byrtek ◽  
Michael Taylor ◽  
Jill Tydell ◽  
Jamie H. Hirata ◽  
...  

Abstract Abstract 4152 Background: While FL is the most common low-grade lymphoma in the US, median age was less than 60 in patients enrolled on pivotal studies that led to our understanding of disease biology and optimal therapy. It remains unclear whether similar disease characteristics, presentation, prognostic factors, treatment patterns, and outcomes pertain to older patients with FL. No clear guidelines exist on how older patients should be treated and data is lacking as to whether current practice patterns affect their survival and progression. Previous reports on FL in the elderly have been retrospective and single center-based. Methods: The NLCS is a prospective, longitudinal multicenter, observational study that enrolled consecutive newly diagnosed FL patients from 3/2004 through 3/2007 collecting data on disease and patients' characteristics, treatment patterns, and outcome. Using the NLCS data we analyzed information on disease stage, grade, FL International Prognostic Index (FLIPI), B symptoms, and treatment choice for patients <60 years, 60–69 years, 70–79 years, and 80+ years. Either Chi-square or Fisher's exact comparison was used to assess the correlations depending on the sample size of the test. Results: A total of 2,736 pts were enrolled, of which 1,215 (44%) were < 60, 708 (25%) were between 60–69, 549 (20%) were between 70–79, and 264 (9%) were >80. There was a significant difference in grade distribution across the different age groups (p < 0.0001), with 22% of pts 80+ having grade 3 FL vs 17% pts <60. No significant differences across age groups in B symptoms, extra nodal sites, or LDH values were observed. A significant difference in FLIPI score was seen across the age groups (p < 0.0001) where high-score FLIPI was present in 48% of pts 80+ as opposed to 16% of pts <60, although calculating FLIPI might be confounded by the fact that older patients were more likely to not have received a bone marrow (BM) exam with 66% of pts 80+ not having BM exam vs. only 40% of those <60 (p < 0.0001). The difference in FLIPI was mainly due to lower Hgb values as older patients were more likely to have had Hgb < 12 g/dL than younger patients (31% of pts 80+ vs. 15% of pts <60) and to age being a component of the FLIPI index. The difference in FLIPI score across age groups was also observed in patients with grade 3 FL where 53% of pts 80+ had poor FLIPI vs. 15% of pts <60 (p < 0.0001). A statistically significant difference in treatment patterns was found across age groups (p <0.0001). When treatment was implemented, older patients were more likely to have received rituximab (R) monotherapy (37% of 80+ vs. 12% of <60) and less likely to have received R+Chemotherapy (40% of pts 80+ vs. 64% of pts<60). In addition, more pts 80+ were observed compared to those <60 (23% vs. 16%). These differences persisted even in those with advanced stage (III/IV), grade 3 disease, region of diagnosis, and in poor-risk FLIPI. When chemotherapy was used, older patients were less likely than younger patients to receive anthracyclines (p < 0.0001) (31% of pts 80+ vs. 69% of pts<60). Anthracycline use remained significantly different regardless of disease stage, grade, or FLIPI score. Conclusions: To our knowledge, this is the largest prospective data collection available for FL pts 80+ years of age. We demonstrate that these pts have higher FLIPI score and grade 3 disease. When treatment is initiated, these patients receive R monotherapy more often than their younger counterpart. Anthracycline use in this population is also less common regardless of disease stage, grade, or risk profile. Whether these baseline differences translate into different outcomes remains to be seen. Disclosures: Nabhan: genentech: Research Funding, Speakers Bureau. Byrtek:Genentech: Employment. Taylor:Genentech: Employment. Hirata:Genentech: Employment. Flowers:Genentech/Biogen-Idec (unpaid): Consultancy; Celgene, Intellikine: Consultancy; Millennium: Research Funding.



2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12516-12516
Author(s):  
S. Manfrida ◽  
G. R. D’Agostino ◽  
C. Anile ◽  
G. Mantini ◽  
G. Colicchio ◽  
...  

12516 Background: We retrospectively evaluate the tolerance and the efficacy of a conventional schedule of radiotherapy in elderly patients with glioblastoma multiforme (GBM). Methods: Eighty-three consecutive patients affected by glioblastomas were treated between 2001 and 2006. We divided our series in two groups: patients under 65 years (n=52) and patients ≥ 65 years old (n=31). In the elderly group, median age was 68 years (range, 65–80). 17 patients (54,8%) were female, 14 male (45,2%); 20 patients (64,5%) <70 years, 11 patients (35,5%) ≥70 years. Among the younger patients, median age was 51 years (range 25–64), male/female ratio 32/20 (61.5%/38.5%).Twenty-seven out of 31 elderly patients (87,1%) were treated with conformal radiotherapy (CRT, 5940 cGy, 180 cGy/day; CTV2: tumor bed + residual tumor if present + oedema, 3960 cGy; CTV1: tumor bed + residual tumor if present + margins, 1980 cGy). Four out of 31 patients received an intensification dose of xxxx cGy by stereotactic conformal radiotherapy (SRT, 12,9%); among the younger patients, 25/52 were treated with CRT (48,1%) and 27/52 with SRT (51,9%). Concomitant and adjuvant chemotherapy was administered by temozolomide (TMZ).Toxicity was evaluated according to RTOG score. Survival analysis were performed using Kaplan-Meier method and log-rank testing was used for comparison of groups. Results: In the elderly group, neurological acute toxicity was observed in 6/31 patients (19,4%), with grade 3 in two patients. In the under 65 group, 5/52 patients (9,6%) had neurotoxicity (Grade 3 in two patients).This difference was not statistically different.At a median follow-up period of 28 months (range, 3–61), median progression-free survival (PFS) was 11 months in the ≥65 group and 10 months in the under 65 group; median overall survival (OS) was respectively 17 months and 22 months. 1- year survival was respectively 77.6% and 74.5%. Conclusions: In our analysis age did not seem to be a limiting factor in the choice of the therapeutic strategy for patients with glioblastoma multiforme. No significant financial relationships to disclose.



1999 ◽  
Vol 17 (8) ◽  
pp. 2412-2412 ◽  
Author(s):  
R. A. Popescu ◽  
A. Norman ◽  
P. J. Ross ◽  
B. Parikh ◽  
D. Cunningham

PURPOSE: The surgical treatment of colorectal cancer (CRC) in elderly patients (age 70 years or older) has improved, but data on adjuvant and palliative chemotherapy tolerability and benefits in this growing population remain scarce. Elderly patients are underrepresented in clinical trials, and results for older patients are seldom reported separately. PATIENTS AND METHODS: Using a prospective database, we analyzed demographics, chemotherapy toxicity, response rates, failure-free survival (FFS), and overall survival (OS) of CRC patients receiving chemotherapy at the Royal Marsden Hospital. The cutoff age was 70 years. RESULTS: A total of 844 patients received first-line chemotherapy with various fluorouracil (5-FU)-containing regimens or raltitrexed for advanced disease, and 543 patients were administered adjuvant, protracted venous infusion 5-FU or bolus 5-FU/folinic acid (FA) chemotherapy. Of the 1,387 patients, 310 were 70 years or older. There was no difference in overall or severe (Common Toxicity Criteria III to IV) toxicity between the two age groups, with the exception of more frequent severe mucositis in older patients receiving adjuvant bolus 5-FU/FA. For patients receiving palliative chemotherapy, no difference in response rates (24% v 29%, P = .19) and median FFS (164 v 168 days) were detected when the elderly were compared with younger patients. Median OS was 292 days for the elderly group and 350 days for the younger patients (P = .04), and 1-year survival was 44% and 48%, respectively. The length of inpatient hospital stay was identical. CONCLUSION: Elderly patients with good performance status tolerated adjuvant and palliative chemotherapy for CRC as well as did younger patients and had similar benefits from palliative chemotherapy.



2018 ◽  
Vol 45 (1-3) ◽  
pp. 213-217
Author(s):  
Zdenka Hruskova ◽  
Vladimir Tesar

Background: Rapidly progressive glomerulonephritis (RPGN) is characterized by a rapid deterioration of renal function and by extracapillary proliferation in >50% of glomeruli. The most common type of RPGN is “pauci-immune” glomerulonephritis caused by anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV). Summary: The incidence of AAV increases with age and pauci-immune glomerulonephritis is the most common diagnosis found in renal biopsies in the elderly population. Age was identified as an independent negative risk factor for both death and end-stage renal disease in AAV, and the mortality of older patients was uniformly higher than in younger patients in all retrospective studies. Early diagnosis may be difficult particularly in elderly patients with renal-limited disease but is important for the good outcome of the patients. Immunosuppressive treatment options include cyclophosphamide or rituximab combined with corticosteroids with or without plasma exchange in case of severe disease. Data from randomized trials are completely missing for patient aged >75 years. Based on retrospective studies, elderly patients seem to respond to immunosuppressive drugs just as younger patients are able to, but they are at a higher risk of adverse events. Key Messages: RPGN is relatively common in the elderly patients. Immunosuppressive treatment in older patients with AAV or RPGN may be useful but needs to be strictly individualized with all the risks taken into consideration. Further studies are needed to examine the role of novel therapeutic options in the elderly population with RPGN.



Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1613-1613
Author(s):  
Thomas Melchardt ◽  
Lukas Weiss ◽  
Clemens Hufnagl ◽  
Daniel Neureiter ◽  
Ralf Kemmerling ◽  
...  

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.



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