Elderly Multiple Myeloma (MM) Patients (≥70 years) Can Safely Undergo Autologous Stem Cell Transplantation (ASCT) but Have Shorter Overall Survival Than Younger Patients (<70 years).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3409-3409
Author(s):  
Carla Borgono ◽  
Young Trieu ◽  
Wei Xu ◽  
Donna E. Reece ◽  
Suzanne Trudel ◽  
...  

Abstract Abstract 3409 Poster Board III-297 Introduction: MM is a disease of the elderly with a median age at diagnosis of 65 years. For younger patients (<65 years), melphalan-based ASCT is standard therapy. However, limited data are available on the efficacy of ASCT in elderly patients (pts) over age 70, with concerns of excess toxicity and transplant-related mortality (TRM). Methods: From October 2000-August 2006, 548 MM pts were transplanted at our institution, 33 of whom (6%) were ≥70 years in age. Baseline demographics, disease characteristics, transplant and survival outcomes, including toxicities were collected retrospectively on all 548 patients and differences between the older patients (≥70 years) vs the younger pts (<70 years) were analyzed. Patients receiving a second salvage or tandem transplant were excluded. As per institutional transplant standard, all patients received 3-6 cycles of high-dose dexamethasone (DEX)-based induction therapy, underwent peripheral blood stem cell mobilization with cyclophosphamide 2.5g/m2 and GCSF 10mg/kg/day, and received melphalan 200mg/m2 for conditioning (no routine dose reductions for age). Ciprofloxacin prophylaxis and GCSF use (from day 7) were used routinely during the transplant process. Results: A total of 548 MM pts were studied: 33 pts ≥70 yrs of age (median 71 yrs; range 70-74); 515 pts <70 years of age (median 59 yrs; range 29-69). Patient and disease characteristics: MM subtypes for all pts included: IgG (59%), IgA (19%), biphenotypic (2%), IgD and IgM (<1%), light chain only (5%), other (10%) (no differences between the 2 groups). For the ≥70 yrs pts at baseline: median Hb was 98g/L (range 73-141), 22% of pts were hypercalcemic at diagnosis (median 2.38 mmol/L; range 2.09-4.24), 48% had significant renal dysfunction with serum creatinine >177 umol/L at diagnosis (median creatinine 94 umol/L; range 60-450), and 79% had elevated serum beta-2 microglobulin at diagnosis (median 269 nmol/L, range 5.8-505). No differences in baseline lab values were noted between the elderly and younger groups. Comorbid disorders in the elderly pts were common: 36% cardiac conditions (hypertension, coronary artery disease, heart failure, arrthythmias), 18% prior or pre-existing malignancy (solid tumours, lymphoma, leukemia), 12% diabetes, 12% gastrointestinal (ulcers, diverticular disease, colitis), 21% prior major infection (sepsis, pneumonia, TB), 6% renal disease (chronic renal failure, cystic disease), 6% CNS (stroke, seizures). Both renal disease and prior major infections were more common in the ≥70 group (renal 6 vs 1%, p=0.04 and infections 21 vs 5%, p=0.0003. Transplant outcomes: Although a standard stem cell mobilizing procedure was utilized for all pts, fewer stem cells (CD34+ cells) were collected in the ≥70 age group in comparison to the younger pts (median 12.3 vs. 9.1 × 106/kg; p=0.004). This did not, however, translate into significant differences in days to neutrophil or platelet engraftment, nor in days of hospitalization. For the ≥70 group, 76% achieved a PR (9% VGPR/CR) as assessed 3 months post-transplant, similar to the <70 group (p=0.08). Median progression-free survival from transplant was similar between groups (23.7 vs 21.8 mos, p=0.65) but median overall survival of the elderly pts was significantly shorter than that of younger patients (46.3 vs 80.4 mos, p = 0.03). Causes of death are unknown. Toxicities: Older patients exhibited cardiac toxicities (primarily arrhythmias) more frequently than younger patients during the transplant period (grade 1/2 - 3% vs 6%, grade 3/4 – 0 vs. 2%; p<0.0001). Treatment-related deaths, however, were uncommon in both groups [none in ≥70 pts vs 1.3% in <70 pts (p=0.27)]. Conclusions: Disclosures: Reece: Ortho Biotech: Honoraria, Research Funding.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2086-2086
Author(s):  
Tanya M. Wildes ◽  
Kristan M. Augustin ◽  
Ravi Vij ◽  
Nancy Bartlett ◽  
John F. DiPersio ◽  
...  

Abstract The incidence of Non-Hodgkins lymphoma (NHL) increases with age. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become a widely applied treatment for advanced NHL. Patients 60 years of age or above are at higher risk for recurrent disease but few studies have addressed the tolerability and outcomes of ASCT in comparison to younger patients conditioned and treated in a homogeneous manner. With this in mind, we compared outcomes of 153 consecutive patients (pts) with NHL who underwent high-dose chemotherapy at our institution between January 1, 2000 and August 31, 2004, focusing on the influence of age at the time of transplant.. All 153 pts received the identical BEAM conditioning regimen followed by ASCT. Ninety four pts were under the age of sixty (median age 51, range 21–59) and 59 were aged 60 or older (median age 64, range 60–74). Supportive care was the same in both groups. We compared data on stem cell mobilization, engraftment, toxicities of conditioning, post transplant morbidity, relapse, and mortality between the older and younger individuals. There were no significant differences in the CD34+ cell doses collected, transplanted, or number of leukapheresis attempts required to achieve an adequate CD34+ cell dose. Older patients experienced significantly more grade 3 mucositis (40% vs 18%) and had higher risks of gram negative bacteremia (20% vs 13%) and candidemia (10% vs 4%) than the <60 group. However, days to transplant discharge, days of neutropenic fever, and days on iv antibiotics were similar. Treatment related mortality was somewhat higher in the ≥ 60 group (8.4% vs 5.3%), but this was not statistically significant (p=0.65). Neutrophil engraftment was similar between both groups but recovery to platelets >20,000/ul (21.5 vs 16 days) and 50,000/ul (33 days vs 23 days) was significantly longer in the older patients despite transplantation of similar CD34 doses (p<0.01 for both comparisons). Both groups were well balanced for proportion of patients with high grade and low grade NHL as well as those in complete or partial remission at the time of transplant. Relapse rates at 2 years did not differ significantly between the two groups (36% in > 60 vs 27% in ≥ 60; p=0.28). With a median of 22 months follow-up, the Kaplan-Meier estimate of two year progression free survival was 74 +/− 5% in the younger group and 61+/− 7% in the older group (p=0.76). In summary, older individuals conditioned with BEAM chemotherapy experience more severe mucosal toxicity than younger patients, which may predispose to higher risk for bacteremia and fungemia. Platelet recovery appears to be prolonged in older individuals, possibly as a result of qualitative stem cell defects or increased mucosal damage. Despite these differences, progression free survival is similar in patients over the age of 60 in comparison to younger individuals. Future efforts should focus on reduction of mucosal toxicity and infectious complications in older patients in order to further reduce morbidity and improve overall outcomes.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1173-1173
Author(s):  
Shaji Kumar ◽  
Martha Lacy ◽  
Angela Dispenzieri ◽  
Suzzane Hayman ◽  
William Hogan ◽  
...  

Abstract Background: High dose therapy with autologous stem cell rescue has been shown to prolong survival in patients with multiple myeloma in randomized controlled trials. However, most of the prospective studies have included younger patients, usually 65 or less. It is important to have a better understanding of the outcome of transplantation in the older patients given the median age of onset of myeloma of 65 years. We retrospectively reviewed our institutions experience with high dose therapy for patients over 70 years. Methods: We identified 35 patients with multiple myeloma, from the transplant database, who were at or over the age of 70 at the time of their high dose therapy. We matched these patients to 70 patients (two matches for each patient), based on stage at transplant (primary refractory, plateau phase, relapse off therapy, or relapse on therapy), Durie Salmon stage, high or low labeling index, conventional cytogenetics (abnormal vs normal), presence or absence of circulating plasma cells at time of transplant, and whether cyclophosphamide was used as part of mobilization in that order of priority. Results: The median age of the two groups were 55.3 (Range 37.3–64.8) and 71.7 (Range 70–75.8) years at the time of transplant. The median time to transplant from diagnosis was similar (6.4 for the older patients compared to 6.9 months for the other, P = NS). Ten of the 35 older patients received reduced dose melphalan (140 mg/2)) compared to 3 patients in the control group; P &lt; 0.01. The median follow up from transplant was 10.1 months for the older patients compared to 18 months for the control group. The overall response rate was similar for the two groups (97.1% for the older patients compared to 95.5 for the control group). Eleven (31%) of the older patients and 17 (24%) of the control patients achieved a CR (P = NS). The post transplant progression free survival estimate at 1 year post transplant was 65.3% for the older patients compared to 66% for the control group (P = 0.3)The two year estimated overall survival from transplant was similar in the two groups; 58% for the older patients compared to 67% for the control group. The overall survival from diagnosis was similar for the two groups (P = 0.6). The median number of days hospitalized was 9 days for the older population compared to 5 days for the control group (P = 0.37). Four patients died within the first one hundred days, one (3%) among the older patient group and 3 (4.3%) in the control group. Conclusions: High dose therapy and autologous stem cell transplantation is feasible in selected patients with multiple myeloma over 70 years. It is likely that these older patients were selected based on their overall performance status, a factor that is difficult to analyze in this retrospective review. Nearly 70% of the elderly patients received full dose melphalan for conditioning (200 mg/m2). The toxicity of transplant as well as the outcome appears to be very similar to the younger patients. Patients with multiple myeloma should not be excluded from high dose therapy solely on the basis of their chronological age.


Blood ◽  
2010 ◽  
Vol 116 (13) ◽  
pp. 2215-2223 ◽  
Author(s):  
Jayesh Mehta ◽  
Michele Cavo ◽  
Seema Singhal

Abstract The clinical approach to older patients with myeloma has to be modified to take into account comorbidities and the likelihood of higher treatment-related toxicity. Individualization of management and adequate supportive therapy are important to obtain the best response while minimizing adverse effects. Corticosteroids, novel agents, conventional cytotoxic agents, and high-dose chemotherapy with autotransplantation (modalities used in younger patients) are also used in older patients, although the elderly undergo transplantation less frequently. The sequential use of active agents singly and in different combinations has improved response rates and survival of all patients with myeloma, including the elderly.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2072-2072 ◽  
Author(s):  
Eden Hailemichael ◽  
Jonathan L. Kaufman ◽  
Christopher R. Flowers ◽  
Edmund K. Waller ◽  
Mary Jo Lechowicz ◽  
...  

Abstract Abstract 2072 Introduction: Many randomized control trials demonstrated that HDT-ASCT is superior to conventional therapies in myeloma patients and prolongs progression free survival (PFS) and overall survival (OS) (Attal M, 1996, Childs JA, 2003). However, in treating a malignancy with a median age of diagnosis of 69 years, the majority of the patients will not be eligible for this beneficial approach if a nominal numerical age cut-off (<65 years) is followed based on the assumption that elderly patients cannot tolerate HDT-ASCT; nor will they be eligible for clinical trials involving HDT-ASCT if stringent age-restricted inclusion criteria are incorporated. Therefore, we have evaluated if the elderly patients benefit from HDT-ASCT. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) 18 registry data (www.seer.cancer.gov) as our comparator (reflects 28% of the US population);to provide information on incidence, prevalence and survival from 1973–2009. The data from an institutional cohort (IC) is obtained from the records of patients that underwent HDT-ASCT from January 2000 to January 2012. We used IBM SPSS version 20 to generate the Kaplan-Meier survival curves. Results: Of the 6,571,117 malignant cases listed in SEER registry, a total of 74,826 cases (1.1%) of multiple myeloma (ICD-03 code 9732) were identified (39735 males and 35091 females). Median age of the patients is 70 years. Among these patients 48,988 patients (65%) are over the age of 65. A total of 901 myeloma patients underwent HDT-ASCT from IC during the evaluable period and 167 patients (19%) were over the age of 65. The median survival for each subset is listed in Table 1. Both male and female WCI-ASCT myeloma patientshad prolonged OS compared to the SEER myeloma patients, despite the difference in magnitude of advantage in IC-ASCT male patients vs. female patients. Both white and black patients, as well as patients undergoing HDT-ASCT across all age subgroups had a significant survival advantage. Conclusions: In each subgroup, by the decade of diagnosis, gender, race, age subsets we have consistently demonstrated a significant survival benefit for IC transplant patients ≥age 65 compared to SEER myeloma patients ≥age 65 if offered HDT-ASCT. Selection-bias prevails in the groups showing improved overall survival. Hence, a careful selection process considering physiologic age as a determinant for transplant eligibility would result in better outcomes, and not preclude the elderly from the survival benefits of HDT-ASCT. Disclosures: Kaufman: Millenium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Onyx: Consultancy. Flowers:Celgene: Consultancy; Prescription Solutions: Consultancy; Seattle Genetics: Consultancy; Millennium: Research Funding, Unpaid consultancy, Unpaid consultancy Other; Genentech: Unpaid consultancy, Unpaid consultancy Other; Gilead: Research Funding; Spectrum: Research Funding; Janssen lymphoma research foundation: Membership on an entity's Board of Directors or advisory committees. Waller:Outsuka: Research Funding.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5223-5223
Author(s):  
Zwi N. Berneman ◽  
An-Sofie Verstraete ◽  
Alain Gadisseur ◽  
Ann Van de Velde ◽  
Wilfried A. Schroyens

Abstract Background: For a long time, multiple myeloma has been a disease with a poor outcome. High dose (melphalan) chemotherapy followed by autologous stem cell transplantation has been reported to improve the overall and progression-free survival of these patients. Objective: To determine the survival of multiple myeloma patients treated with conventional chemotherapy and compare it with that of patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. Design/Methods: 83 myeloma patients treated at a single institution were included in this retrospective study. They were divided into two groups: one group of patients who were received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (n=42) and one group of patients who only received conventional chemotherapy and were eventually also treated with thalidomide and/or corticosteroids (n=41). The distribution of the stages of the disease according to Salmon and Durie were similar in both groups of patients. For both groups, the overall and progression-free survival was calculated. Results: In the general analysis, myeloma patients who underwent an autologous transplant had a significantly longer overall survival (58.8 vs. 52.2 months, p=0.036) and progression-free survival (39.6 vs. 11.8 months, p &lt; 0.001) in comparison with the conventional chemotherapy group. If analysis was restricted to those patients who were transplanted as a first-line treatment, there was no significant difference in overall survival in comparison with conventional chemotherapy (51.8 vs. 52.2 months, p= 0.422); progression-free survival was significantly better in the first-line transplant arm as compared to the conventional chemotherapy arm (35.4 vs. 11.8 months, p= 0.003). As the median age in the transplant arm was significantly lower than in the conventional chemotherapy arm, we also performed a sub-analysis of patients who were between 60 and 70 years of age at diagnosis; there was no significant difference in overall survival between the two groups (60.7 vs. 69.5 months, p= 0.656), while the progression-free survival was again better in the autologous transplant group as compared to the conventional chemotherapy group (41.0 vs. 8.4 months, p= 0.020). Conclusion: High-dose chemotherapy and autologous stem cell transplantation in the treatment of myeloma is associated with improved progression-free survival and in the general analysis, with improved overall survival. The overall survival of patients who were only treated with conventional chemotherapy is somewhat higher (more than 4 years) as compared to that of historical controls (2–3 years).


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1878-1878
Author(s):  
Morie A Gertz ◽  
Shaji Kumar ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
David Dingli ◽  
...  

Abstract Abstract 1878 Poster Board I-900 Autologous stem cell transplant as a platform for multiple myeloma treatment is the standard of care for patients who can safely withstand the procedure. Before novel agents were introduced, one-third to one-half of patients did not achieve partial response at transplant. Previously published medical literature has showed that in this past era, absence of initial response to induction therapy had no impact on progression-free survival and overall survival after high-dose therapy. Lack of response to initial induction did not preclude a good response after stem cell transplant. With the introduction of novel agents—immunomodulatory drugs and proteasome inhibitors—response rates with initial therapy are now between 70% and 100%. This retrospective study analyzes progression-free survival and overall survival in patients who do not have a partial response after induction therapy with a regimen that contains a novel agent. Unlike patients in reports published previously—before novel agents—patients who do not achieve partial remission have a significantly shorter overall survival from transplant (74.0 vs 43.5 months) and a shorter progression-free survival (22.6 vs 13.1 months; P<.001). Absence of a response to induction therapy with a novel agent predicts a poorer outcome after high-dose therapy.{abstabft}.b CR+VGPR for plateau, P<.001 compared with other 3 categories. Failure to respond to novel-agent induction leads to shorter posttransplant progression-free survival (PFS). Failure to respond to novel-agent induction leads to shorter posttransplant overall survivalDisclosures: Gertz: celgene: Honoraria; millenium: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Kumar: celgene: Honoraria; millenium: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Lacy: celgene: Honoraria; millenium: Honoraria.TableMultivariable Analysis of Posttransplant Progression-Free SurvivalVariableP ValuePlateau vs relapsed-refractory.003Albumin.86Sex.94b2-Microglobulin.89Bone marrow plasma cells.18Age.75Abnormal cytogenetics.002CTX mobilization.51Labeling index.002


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3230-3230
Author(s):  
Philip T Murphy ◽  
Cherisse Baldeo ◽  
Patrick O'Kelly ◽  
Jeremy Sargant ◽  
Patrick Thornton ◽  
...  

Abstract In myeloma, the use of autologous stem cell transplantation in younger patients as well as the introduction of thalidomide, lenalidomide and bortezomib has resulted in improvement in long-term survival of both younger and older patients. Bortezomid and high dose dexamethasone is currently recommended to treat newly diagnosed myeloma patients presenting with renal impairment and may lead to varying degrees of improvement in renal function. We have assessed not only survival trends for all patients diagnosed at our centre over the past 18 years but also the survival of the subset of patients with severe renal impairment who required dialysis at diagnosis. All patients diagnosed with myeloma at our centre between January 1995 and December 2012 were included. We constructed Kaplan-Meier curves and used the Breslow generalised Wilcoxon test to evaluate overall survival (OS) patterns (diagnosed in three calendar periods: 1995-2000; 2001-2006; 2007-2012) for our total patient population as well as the subset of patients who required dialysis within 4 weeks of diagnostic bone marrow test. 262 patients (60.3% males) were diagnosed between 1995 and 2012. For all patients, median OS significantly increased from 13.2 months in period 1995-2000 to 27 months in period 2001-2006 with median OS not yet reached in period 2007-2012 (p=0.0001). In patients 70 years old or less, median OS significantly increased from 25.4 months in period 1995-2000 to 46.7 months in period 2001-2006 with median OS not yet reached in period 2007-2012 (p=0.0482). Improved median OS was also seen in patients > 70 years old: 4.4 months in period 1995-2000, 17.4 months in period 2001-2006 and 25.1 months in period 2007-2012 (p<0.0001). In contrast, patients requiring dialysis at diagnosis (n = 44) had much worse outcomes: median OS in the period 1995-2000 was 2.8 months and although there was a slight improvement in median OS in the period 2001-2006 (p=0.0318), there has been no further improvement in median OS in the period 2007-2012. In our overall myeloma patient population, median OS has continued to increase over the time periods 1995-2000, 2001-2006 and 2007-2012, both for younger patients 70 years old or less and older patients >70 years old. Patients requiring dialysis at diagnosis, however, continue to have much poorer median OS, despite the use of bortezomib and dexamethasone containing regimens in recent years. The possible benefit of improved supportive measures and the early use of other emerging novel agents in this poor prognostic subgroup should be explored in the clinical trial setting. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3951-3951
Author(s):  
Viet Q. Ho ◽  
Robert Cade ◽  
Gene A. Wetzstein ◽  
Van D Hoang ◽  
Alan List ◽  
...  

Abstract Background The optimal induction regimen for patients with acute myeloid leukemia (AML) remains unclear. Intensification of daunorubicin (DNR) dose during induction chemotherapy (90 mg/m2) in younger patients with AML has yielded improved complete remission (CR) rates and overall survival (OS) compared to 45 mg/m2. To date, daunorubicin 90 mg/m2 has not been compared to idarubicin for induction in younger patients. Herein, we compare induction outcomes using cytarabine plus either IDA or DNR 90 mg/m2 as induction chemotherapy in patients less than 65 years of age. Methods This is a single institution case controlled retrospective study evaluating patients aged 18 to 65 years who received induction chemotherapy for AML with either cytarabine 100 mg/m2 x 7 days and DNR 90 mg/m2 x 3 days or cytarabine 200 mg/m2 x 7 days and IDA 12 mg/m2 x 3 days at Moffitt Cancer Center (MCC). Patients who achieved CR were offered consolidation chemotherapy and/or allogeneic transplant as per standard guidelines. Clinical endpoints that were measured and compared include CR, OS and leukemia free survival (LFS). Patients were censored at time of transplant. Categorical variables were compared using Chi square test, and t- test for continuous variables. Cox regression was used for multivariate analysis. Remission rate were compared using Chi square test. Kaplan-Meier estimates were used for OS and LFS and Log Rank test was used to compare groups. All analyses were conducted using SPSS version 21. Results Between January 2005 and April 2013, 175 patients<= 65 years with newly diagnosed AML were included; 84 patients received induction chemotherapy at MCC with high dose DNR and 91 patients received IDA as described above. Baseline characteristics were similar between the two groups (Table 1). The median duration of follow up was 25.9 months. CR rates were similar between the DNR and IDA (74% vs 76%, p = 0.95). Rates of CR after first induction were also similar (61% vs 62%, p = 0.33). The median LFS was 10.2 months with DNR compared to 6.4 months with IDA (p=0.476) (Figure 1). Median OS was not reached in the DNR arm compared to the 18.4 months in the IDA arm (p=0.107) (Figure 2). No significant differences were observed in the number of patients receiving consolidation chemotherapy (70% vs 66%, p = 0.54) or allogeneic stem cell transplant (23% vs 25%, p = 0.68). There was no difference in 60 day mortality during induction chemotherapy (4.8% vs 5.5%, p = 1.00). In multivariate cox regression analysis anthracycline selection did not affect OS after adjusting for cytogenetic and molecular profile, CR, consolidation received or stem cell transplantation (hazard ratio, 1.25; 95% CI, 0.74-2.09; p = 0.402). Conclusion In younger adults with AML, induction chemotherapy with either IDA or DNR yielded similar rates of CR and LFS and OS. However, a trend towards increased overall survival was observed in the DNR cohort, adding further support to the use of high-dose daunorubicin as standard induction for AML. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1863-1863
Author(s):  
Akiva Diamond ◽  
Sabarish Ram Ayyappan ◽  
Raisa Pinto ◽  
Ehsan Malek ◽  
Ben K. Tomlinson ◽  
...  

Abstract Introduction: The prognostic relevance of age at diagnosis has long been recognized in DLBCL. Its role in the biology of disease has not been clarified, and it has been postulated that the worse prognosis of older DLBCL patients is a result of more aggressive disease combined with poor tolerance to aggressive therapy. The introduction of rituximab has improved the outcomes of DLBCL in all ages, whereas reduced dose and anthracycline-free regimens have improved access of elderly patients to more effective DLBCL therapy. Methods: We accessed the Hematologic Malignancies database of University Hospitals Seidman Cancer Center for DLBCL patients diagnosed between 2002 and 2014. Information collected included demographic as well as baseline laboratory and disease characteristics. Relapse and overall survival times were calculated from end of therapy and time of diagnosis, respectively, using the Kaplan Meier method, comparisons were done using the log-rank test. Cumulative incidence of major cardiovascular events (including myocardial infarction, coronary artery disease without infarction, congestive heart failure and arrhythmias) were calculated using death as competing risk; comparisons between groups were done using the Gray test. Results: A total of 400 DLBCL patients were identified, 95 were older than 75 years. Table 1 shows the baseline demographic and disease characteristics. Older patients had a higher incidence of comorbidities and higher rates of decreased performance status. There were no other differences in baseline disease characteristics. A smaller proportion of older patients proceeded to receive antineoplastic therapy (81% vs. 91%, p = 0.002). Therapy for older subjects was less intense (full dose R-CHOP 54.5% vs. 81.1%, p<0.001) with more planned and unplanned dose reductions (48% vs. 11%, p<0.001). Despite less intense therapy, response rates were not statistically different between the two age groups (84% vs. 87%, p = 0.687). After a median of 28 months follow up, estimated 3-year overall survival was 51% (95% CI 40-61.8%) for patients >75 years vs. 76% for younger patients (95% CI 70.6-80.9%)(p<0.001). In patients who received therapy (n=77 older than 75 years; n=281 for < 75 years), there was no difference in relapse-free survival from the start of treatment (3-year RFS: 77% (95% CI 66.5-88.5%) for patients > 75 years and 65% (95% CI 59.1-71.6%) for younger patients, p=0.155). The cumulative incidence (CI) of cardiovascular events, with death due to any other cause as a competing risk, was higher in subjects >75 years: 1-year CI was 15.3% vs. 7.6% in younger patients (p = 0.04). Conclusions: DLBCL patients older than 75 years have a higher mortality risk following DLBCL diagnosis than younger patients, despite having similar response rates and relapse free survival. While chemotherapy dose reduction does not appear to affect disease control, high rates of cardiovascular events suggest future studies should focus on the minimization of short and long term toxicities of therapy. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4521-4521
Author(s):  
Akshay Sharma ◽  
Minghui Duan ◽  
Michael Graiser ◽  
Hongzheng Zhang ◽  
Amelia Langston ◽  
...  

Abstract Abstract 4521 Background: About 1/3 of advanced Hodgkins lymphoma (HL) patients fail first line therapy and are candidates for autologous stem cell transplantation (ASCT). Studies describing the outcomes of relapsed/refractory HL in adults have shown that the long-term survival is about 40–60%, following treatment with high dose chemotherapy and ASCT. Surveillance, Epidemiology and End Results (SEER) data indicates that children/adolescents with HL have different disease characteristics from adults (Bazzeh et al, Leukemia and Lymphoma 2010), which we hypothesized could lead to different ASCT outcomes. The aim of this study was to describe the demographic distribution of relapsed/refractory HL patients requiring ASCT at a major transplant center and to study the overall survival (OS) post ASCT with age as a covariate. Patients and Method: We performed an IRB approved, retrospective analysis of a combined cohort of adult and pediatric HL patients undergoing ASCT at Winship Cancer Institute at Emory University and Children’s Healthcare of Atlanta from 1995 to 2011. A total of 131 patients were included in the study (adult=112, pediatric=19). Demographics of patients include: 54% male, 65% Caucasians, 26% African American. The mean age of diagnosis was 30 ± 12 years and the mean age at transplant was 33 ± 13 years. Patients were divided into two categories, younger (≤35 years, n=96) and older (>35 years old, n=35), based on the bimodal distribution of the incidence of HL observed in the SEER database (first peak in the age group 15–35 years and the second one around 55 years). Overall survival was compared using Kaplan Meier estimates for the time-to-event analysis and log rank test for comparing the two groups. Predicted survival for individuals of different ages (in the absence of cancer) was derived from Social Security Administration life tables. Result: As expected from the incidence data in the SEER database, there was a bimodal distribution of age at diagnosis among HL patients undergoing ASCT for relapsed/refractory disease, with a first peak at 25 years and the second peak at 46 years [Figure 1]. 75% patients had nodular sclerosing histology, 8% had mixed-cellularity and 6% had the lymphocyte predominant histological subtype. The distribution of histological subtypes did not differ by age. A univariate analysis revealed that patients with age > 35 years had significantly higher post-transplant mortality (p=0.037) than those ≤35 years [Figure 2]. A multivariable model that included age ≤35, histology, disease status at transplant and chemo-sensitivity indicated that only one of these variables (age) was explanatory in the model. Conclusion: As expected by the increased suitability of ASCT for younger patients, the number of patients ≤35 years undergoing ASCT for refractory/relapsed HL was much higher than the number of older patients. Overall survival of older HL patients who underwent ASCT was worse than that for younger HL patients, likely due to differences in supportive care, toxicity from treatments, and comorbid diseases. The age related differences in post-transplant survival were not explained by the decreased actuarial life expectancy of older subjects based upon life-table projections of survival for the general population. The bimodal distribution in the incidence of HL, and the inferior survival of older HL patients undergoing ASCT suggests that there may be differences in the biology of the disease based upon the age at which HL is diagnosed. Alternative strategies for autologous transplantation of older patients with relapsed/refractory HL are needed. Disclosures: Flowers: Genentech/Roche (unpaid): Consultancy; Celgene: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Spectrum: Consultancy, Research Funding; Novartis: Research Funding; Seattle Genetics: Consultancy.


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