Elderly Lymphoma Patients Research Articles

Association between Lactate Dehydrogenase Levels to the Response of Non-Hodgkin Lymphoma in Elderly Patients Who Treated with First-Line Chemotherapy in Sanglah General Hospital.

BACKGROUND:Non-Hodgkin Lymphoma (NHL) is a malignant haematological disease originates in the lymphocytes, caused by an abnormality in lymphocytes development which forms a tumour and may become cancer. Chemotherapy is the main treatment modality for aggressive lymphoma, but only a few patients achieve remission. Several factors such as age, clinical stadium, number of extranodal regions, and Lactate Dehydrogenase (LDH) level played a role in determining response to chemotherapy.AIM:To measure the association between LDH levels to prognosis of NHL in elderly patients who treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy in Sanglah General Hospital.METHODS:This study used a retrospective descriptive study on elderly NHL patients in Sanglah General Hospital from January until December 2014. The evaluation was measured using the IPI score to determine the prognosis of patients. Demographic data, the stadium, extranodal region, LDH level, and response to chemotherapy were recorded.RESULTS:Twenty-five patients were included in the study. The age ranged was between 61-76 years old (Mean 65,68 ± 4,7 years; Median 65 years). The number of male patients was 19 (76%). Diffuse Large B-Cell Lymphoma (DLBCL) is the most common histopathological structure observed on the patients (68%). LDH levels were normal in 51.6% of the patients and considered high in the rests (48.4%). Results of the chemotherapy were a good response in 72.2%. Compared to the patients who showed complete response to chemotherapy, patients with no response (partial response and progression) had significantly higher levels of LDH (OR: 13,1; 95% CI: 1,36-126,30; p = 0,001).CONCLUSION:Non-Hodgkin Lymphoma in elderly patients with no response to chemotherapy had significantly higher levels of LDH than patients with complete response.

AGE IS NOT IMPORTANT IN FIT ELDERLY PATIENTS WITH AGGRESSIVE LYMPHOMA

Introduction: High-dose chemotherapy followed by autologous hematopoietic cell transplantation (auto HSCT) is an effective salvage therapy for patients with relapsed chemosensitive non-Hodgkin's lymphoma (NHL). Retrospective analyses suggest that the benefit of HDT extends to elderly patients with NHL, which is an important finding considering that the median age at diagnosis is 67 years (range: 65-74) for NHL in United States, using 2010-2014 US SEER data. We aimed to define the efficacy and toxicity of auto HSCT in patients >60 years with NHL. Methods: From January 2005 through January 2019, data from 29 patients (M/F: 21/8; median age: 63 years) with aggressive NHL above 60 years of age who were eligible for auto HSCT according to geriatric assessment (GA) were evaluated. All these data were obtained from the Ankara University Faculty of Medicine, Department of Hematology and Bone Marrow Transplant Unit. Their diagnosis were as following; 17 diffuse large B cell lymphoma (primary refractory or relapsed disease), 8 mantle cell lymphoma (first complete remission), 2 follicular lymphoma, 1 anaplastic large cell lymphoma and 1 peripheral t cell lymphoma. We compared the toxicity profile and outcome between the research group: patient aged 60 years and above and the control group: patient <60 years. Results: All of the patients were stage III or IV at diagnosis; 13 out of 29 elderly patients had active disease at the time of auto HSCT. The median follow-up was 14.1 months (range, 1-60 mos). Prior to transplantation majority (79.3 %) of the elderly patients received BEAM protocol as conditioning treatment. Bone marrow stem cell was used in only 1 patient None of the patient had mobilization failure, the median peripheral CD34 level was 4.75 x106/kg. Twenty-one percent of the patients experienced ≥ grade 2 mucositis and 76 % of the patients had microbiology-documented infection. Fifty-four percent of the patients had diarrhea with median duration of 8 days (range, 5-20 days). Renal toxicity was occurred in 7 (27%) patients while hepatic toxicity in 3 (12.5 %) patients. Median time to neutrophil recovery was 10 days (range, 8-18 days) and platelet recovery 11 days (range, 10-32 days). Overall response was obtained from all patients (23% CR). At the time of data collection, 4 patients (15%) of patients’ ≥ 60 years have deceased. Relapse (n=3) was the main course of death. The probability of 4-year progression free survival (PFS) and estimated overall survival (OS) in elderly patients were 37.5 % and 78.1 %, respectively. Conclusions: Based on this single center study, auto-HSCT is safe and efficacious in the treatment of elderly lymphoma patients. We emphasize the need for further research in order to determine the risk-benefit threshold for HSCT based on age coupled with comorbidity and fragility. Keywords: autologous stem cell transplantation (ASCT); elderly; non-Hodgkin lymphoma (NHL).

Cyclophosphamide dose adjustment based on body weight and albuminemia in elderly patients treated with R-mini-CHOP.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in elderly patients, and R-CHOP chemotherapy is the standard treatment protocol for DLBCL. Elderly patients (often defined as 75 years of age) are treated with anticancer drugs with precaution; however, the pharmacokinetics and pharmacodynamics (PK and PD) of these agents have not been thoroughly investigated in this population. In this study, we investigated the PK of cyclophosphamide (CP) and doxorubicin (DOXO) in elderly patients in order to verify if there is an influence of age on the PK of these anticancer drugs. This is a prospective multi-center clinical trial investigating the PK of CP and DOXO in elderly and very elderly patients with DLBCL treated by R-mini-CHOP regimen. Dose levels were 25 mg/m2, 0.7-1.4 mg/m2, 750 mg/m2, and 375 mg/m2 for DOXO, Vincristine (VCR), CP, and Rituximab, respectively. For PK analysis, 7 time point samples were collected over 48h post-administration on cycle 3. CP and VCR plasma concentrations were measured using UPLC-MS/MS validated method. DOX plasma concentrations were measured using UPLC coupled with fluorescence detection-validated method. PK-POP modeling has been performed with a non-linear mixed-effect model program (Monolix). 31 patients (15 males and 16 females), 75 to 96 years old, were treated with R-miniCHOP protocol. Among them, 19 patients were treated with VCR. A one-compartment (1cpt) open model with linear elimination adequately described CP concentration-time courses. The population PK parameters for CP were: CL = 3.58 L/h, Vmale = 32.2 L, and Vfemale = 28.7 L. Body weight (BW), albuminemia, and gender demonstrated a significant impact on CP PK. A 2-compartment (2cpt) open model with linear elimination best described DOXO concentration-time courses. The population PK parameters for DOXO obtained for the structural model were: CL = 51.1 L/h, Q = 49.6 L/h, V1 = 29.4 L, V2 = 1,130 L (clearances: CL, Q, volumes of distribution: V1, V2). The main covariate effects on DOXO PK were related to gender, BW, and VCR administration. VCR increases DOXO V1 from 29.4 L to 57.5 L (p = 0.02). No hematologic and cardiac grade 3 or 4 toxicity were recorded. Usually, in the absence of specific data, the majority of the physicians empirically reduce anticancer drug dose in the elderly patients (Tourani in J Geriatr Oncol 3(1): 41-48, 2012), or even does not treat these very-old patients. A better knowledge of the pharmacokinetics in very-old patients should allow a better dose adjustment based on the most significant physiological factors that modify the pharmacokinetic parameters. In this study, no serious toxicity was observed in these very elderly patients (84.1 years). This indicates that dose adjustment of chemotherapies should not only be based on age and creatinine clearance, but also, based upon appropriate physiological and biological data. Our findings indicate that, CP dose adjustment should be done according to serum albumin levels and patients BW and gender.

Functional Predictors of Chemotherapy Toxicity in Elderly Lymphoma Patients: A Prospective Pilot Study

Introduction: Treatment of lymphoma, while subtype specific, often includes curative intent combination chemotherapy. There is little evidence on which to base treatment decisions for older patients, and oncologists often rely on their clinical impression and the patient's chronologic age to make treatment decisions. Objective measures may be more accurate and reproducible in predicting eligibility for combination chemotherapy; however their utility in the clinical setting is still under investigation.Objective: The objectives of this pilot study were to assess the feasibility of applying the Hurria (Hurria et al. JCO 2011) and CRASH (Extermann et al. Cancer 2012) chemotherapy toxicity risk stratification measures, as well as physical performance tests, during busy outpatient clinics, and their ability to potentially predict chemotherapy toxicity.Methods: This is a prospective, single centre pilot feasibility study in patients 70 years of age or older, with lymphoma, planned for definitive systemic chemotherapy. Patients completed geriatric tools (eg. Hurria and CRASH questionnaires, gait speed test and grip strength, CSHA Clinical Frailty Scale and Charlson Comorbidity Index) at baseline. Physical performance tests were repeated with each treatment cycle and data were collected on toxicities, hospital admissions, as well as change in treatment cycles or dosing. Primary outcomes were feasibility and time needed to complete the measures; secondary outcomes were correlation between chemotherapy toxicity and geriatric assessment results, and other patient characteristics (stage and ECOG status).Results: Thirty patients have been enrolled to date (out of a target of 30), and 29 have completed all follow-up assessments, with a median age of 77 yrs (range 69-90) for the whole group, and 59% being male. Diagnosis was diffuse large B cell lymphoma in most (59%), followed by CLL (17%), indolent lymphoma (10%), and other (14%). Chemotherapy treatments most commonly included RCHOP (59%), and bendamustine and rituximab (24%). Aggressive histology pts received G-CSF as 1° prophylaxis. The chemotherapy was dose reduced by the treating physician at cycle 1 in 8 patients (28%), and during the course of treatment in 3 pts (10%). Using the Hurria risk stratification score, 7 pts (24%) were low, 17 (59%) were intermediate and 5 (17%) high risk for chemotherapy toxicity. Similarly, the CRASH scoring identified 2 pts (7%) as low, 11 (38%) as medium-low, 14 (48%) as medium-high and 2 (7%) as high risk. The median amount of time needed to complete the Hurria tool was 2 min (1-5 min) vs. 20 min (5-30min) for the CRASH score. Fourteen pts (48%) experienced CTCAE grade 3-5 toxicity, for a total of 25 severe AEs. The most common gr ≥3 AEs was febrile neutropenia (4 pts), anemia and thrombocytopenia (3pts each); other severe AEs, such as upper GI bleed, PE and DVT, rapid atrial fibrillation, and hyponatremia occurred in one pt each. Dose delays occurred in 9 pts (31%) and 5 pts (17%) required hospitalization due to toxicity. The CSHA frailty score and grip strength worsened throughout treatment and had not recovered by the 1 month visit post-treatment, while the 6 meter walk time did not significantly vary over time during treatment (Figure 1). On univariate analysis, the CSHA frailty score and grip strength changes over time, and the Hurria risk score at baseline were significantly associated with any adverse event, while only the CSHA frailty score and Hurria risk score were associated with Grade 3 or higher events (Tables 1 and 2). On multivariate analysis, the CSHA Frailty score and Hurria risk score retained significance for any AE, however when adjusted for CSHA Frailty, the Hurria score was no longer a significant predictor.Conclusion: When perceived fit older patients are treated with full-dose systemic chemotherapy, the rate of toxicity is high. The Hurria tool, takes a short time to administer, and while not previously tested in lymphoma patients, appears to predict toxicity. The CSHA Frailty was the most robust predictor of chemotherapy toxicity in our patient population, and is a very simple measure to administer. The results of this pilot has led us to recommend routine use of these tools in all older lymphoma patients undergoing systemic chemotherapy at our centre, with the aim of further testing their ability to predict chemotherapy toxicity and treatment outcomes, as well as help plan co-interventions. DisclosuresKuruvilla:Abbvie: Consultancy; Princess Margaret Cancer Foundation: Research Funding; Leukemia and Lymphoma Society Canada: Research Funding; Lundbeck: Honoraria; BMS: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Amgen: Honoraria; Roche: Consultancy, Honoraria, Research Funding; Karyopharm: Honoraria; Merck: Consultancy, Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria. Crump:Jansen-Ortho: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy; Servier Canada: Consultancy.

Hodgkin lymphoma in elderly patients.

We aim to summarize the current knowledge on the treatment of elderly Hodgkin lymphoma patients with a focus on evidence from clinical trials and novel drugs. For elderly Hodgkin lymphoma patients above 60 years without precluding comorbidities a curative treatment approach is warranted. Early favorable stage patients should receive two cycles of multiagent chemotherapy followed by 20 Gy localized radiotherapy. Early unfavorable stage patients should receive four cycles of multiagent chemotherapy followed by 30 Gy localized radiotherapy. For advanced stage patients six cycles of multiagent chemotherapy can be recommended and should be followed by localized radiotherapy on residual disease manifestations. Relapsed or refractory patients should be treated in an individually tailored approach that considers both the patient's objectives and comorbidities. The antibody-drug conjugate brentuximab vedotin is a very effective option for elderly patients with a high response rate albeit limited durability. Anti-programed cell death protein 1 antibodies might also be effective in elderly Hodgkin lymphoma patients with a mechanism of action distinct from chemotherapy. In conclusion, the goal of treatment in newly diagnosed elderly Hodgkin lymphoma patients is curative whenever possible and prospective and retrospective evidence has shown that this is feasible for all disease stages with a variety of multiagent chemotherapy regimen. Relapsed and refractory elderly Hodgkin lymphoma patients can mostly only be treated with the goal of palliation. However, it remains to be seen if novel substances and new combination regimen are able to change that.

Autologous hematopoietic stem cell transplant is safe for elderly lymphoma patients

Autologous hematopoietic stem cell transplant is safe for elderly lymphoma patients

Abstract 4225: Myelodysplastic syndrome and acute myeloid leukemia following use of chemo-immunotherapy and granulocyte colony-stimulating factors among elderly non-Hodgkin lymphoma patients

Abstract Purpose The purpose of this study was to examine use of granulocyte colony-stimulating factors (G-CSF) in relation to risk of myelodysplastic syndrome and acute myeloid leukemia (MDS/AML) in a population-based cohort of elderly patients with non-Hodgkin lymphoma (NHL). Methods We conducted a retrospective cohort study of adults ages 66 years and older diagnosed with first primary NHL between 2001 and 2011 using the Surveillance Epidemiology and End Results (SEER)-Medicare linked database. Patients were included if they were alive and without documented secondary primary cancer at three months post-diagnosis. Using a validated algorithm with Medicare claims and SEER records, we identified MDS/AML cases, primary NHL treatment received (i.e., chemo-immunotherapy and radiation) and type and number of doses of G-CSF received (i.e., filgrastim and/or pegfilgrastim). We determined the risk of developing MDS/AML at 12 months or longer after NHL diagnosis. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for MDS/AML risk associated with G-CSF use in cause-specific Cox proportional hazards models, stratified by treatment to account for confounding by indication. Results A total of 18,245 patients were included with a mean age of 76 years and median follow up of 3.5 years. Most patients were diagnosed with diffuse large B-cell lymphoma (34%) and follicular lymphoma (22%). Fifty-six percent of all patients received chemo-immunotherapy, among whom most received rituximab-based chemotherapy (74%) or monotherapy (18%). G-CSF was most commonly used among those who received rituximab plus chemotherapy (77%). Subsequent MDS/AML was observed in 666 (3.7%) patients. Overall, we found a modest increased risk of MDS/AML with any use of G-CSF (HR=1.28, 95% CI 1.01-1.62); although, a linear trend was observed with increasing number of G-CSF doses (P&amp;lt;0.001). Among patients receiving rituximab plus chemotherapy, risk of MDS/AML was highest in those receiving 10 or more G-CSF doses (HR=1.64, 95% CI 1.14-2.37). When analyzing specific G-CSF agents, this increased MDS/AML risk was consistently observed with filgrastim (10+ doses: HR=1.67, 95% CI 1.25-2.23), but not with pegfilgrastim (10+ doses: HR=1.11, 95% CI 0.84-1.45). Conclusions In this study of elderly NHL patients, we observed a higher MDS/AML risk among those receiving chemo-immunotherapy and G-CSF that was specific to higher number of filgrastim doses but not pegfilgrastim. The benefits of preventing complications from therapy-related neutropenia in patients receiving highly myeloablative treatments likely outweigh the risk of this rare but serious second primary cancer. Understanding differential risk by type of agent warrants further study with the increasing use of G-CSF and FDA-approved biosimilar products (filgrastim-sndz) newly available. Citation Format: Kellyn M. Moran, Zhaoju Wu, Sruthi Adimadhyam, Todd A. Lee, Brian C. Chiu, Gregory S. Calip. Myelodysplastic syndrome and acute myeloid leukemia following use of chemo-immunotherapy and granulocyte colony-stimulating factors among elderly non-Hodgkin lymphoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4225.

A retrospective study of double-hit lymphomas in elderly patients (&gt; 70 years): Overall outcomes.

e19530Background: Double-hit lymphomas (DHLs) are high-grade diffuse large B-cell lymphomas with concurrent translocations involving myc and bcl-2 and/or bcl-6. A patient with DHL often has advance...

Gemcitabine-oxaliplatin plus rituximab (R-GemOx) as first-line treatment in elderly patients with diffuse large B-cell lymphoma: a single-arm, open-label, phase 2 trial

The combination of rituximab, gemcitabine, and oxaliplatin (R-GemOx) has shown high efficacy with a low toxicity profile in elderly patients with relapsed and refractory diffuse large B-cell lymphoma. We aimed to evaluate the efficacy, safety, and feasibility of the R-GemOx regimen as a first-line treatment in elderly patients with diffuse large B-cell lymphoma. In this single-arm, open-label, phase 2 clinical trial, we enrolled patients with previously untreated, histologically confirmed, CD20-positive diffuse large B-cell lymphoma, aged 70 years or older, or aged 60-69 years with an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or greater. Patients were recruited from Jiangsu Province Hospital (Jiangsu Sheng, China). The R-GemOx regimen was administered intravenously: rituximab 375 mg/m2 on day 0; gemcitabine 1 g/m2 on day 1; and oxaliplatin 100 mg/m2 on day 1. The cycle was repeated every 14 days. Six cycles were planned if the patient achieved at least partial remission after the interim assessment. The primary endpoint was the proportion of patients who achieved an overall response at the end of treatment (defined as complete response plus partial response). Analyses were done by intention to treat. The trial is ongoing but no longer recruiting patients. This study is registered with ClinicalTrials.gov, number NCT01670370. Between Aug 22, 2012, and Dec 31, 2015, 60 patients were enrolled and included in the study. The median age of the patients was 75 years (IQR 70-80) and 27 (45%) patients had a poor performance status with an ECOG score of 2 or greater. 45 (75%) patients achieved an overall response at the end of the treatment, with 28 (47%) achieving a complete response. Common grade 3-4 adverse events were haematological toxicities (thrombocytopenia in five [8%] patients, anaemia in four [7%], and neutropenia in nine [15%]) and gastrointestinal complications (nausea in five [8%] patients, vomiting in three [5%], and diarrhoea in one [2%]). No treatment-related deaths were reported. The R-GemOx regimen shows high efficacy and safety as a front-line treatment in an elderly patient subpopulation and might be a therapeutic option for management of diffuse large B-cell lymphoma in elderly patients. National Natural Science Foundation of China, Jiangsu Province's Medical Elite Programme, Project of National Key Clinical Specialty, National Science & Technology Pillar Program, Jiangsu Provincial Special Program of Medical, and National Science and Technology Major Project.

A Retrospective Study of Double-hit Lymphomas in Elderly Patients (Aged > 70 Years): Overall Outcomes

BackgroundDouble-hit lymphomas (DHLs) are high-grade diffuse large B-cell lymphomas with concurrent translocations involving myc and bcl-2 and/or bcl-6. A patient with DHL often has advanced disease at presentation and typically responds poorly to standard therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). More intensive treatment regimens have been studied; however, few data are available on the outcomes in elderly patients (aged > 70 years) treated with these therapies. We retrospectively studied the efficacy and tolerability of chemotherapy regimens in elderly patients within the Advocate Healthcare System. Materials and MethodsA system-wide search of patients treated from 2012 to 2017 was completed to identify patients with c-myc with bcl-2 and/or bcl-6 translocations using fluorescence in situ hybridization. The patients were reviewed for the following: age at diagnosis, stage, lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, chemotherapy details, grade 3/4 toxicities, and response to therapy. Overall survival (OS) and event-free survival (EFS) were calculated. ResultsWe identified 17 patients (9 men and 8 women) with a median age of 73 years (range, 70-89 years). Six patients received R-EPOCH (rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin), 5 received R-CHOP, 1 received bendamustine and rituximab, 1 received the MaGrath regimen, and 1 received cyclophosphamide and rituximab. Three patients were not treated and were referred to hospice care. For all patients, the median follow-up period was 25 months, the EFS and OS were 28% at 36 months, and the median survival was 7.5 months. For patients treated with R-EPOCH, the EFS was 33% at 24 months. For the R-CHOP group, the EFS was 40% at 24 months. Most common grade 3/4 toxicities were neutropenia, anemia, thrombocytopenia, and infections and were more common in the R-EPOCH group. Three patients each died in the R-EPOCH and R-CHOP groups. ConclusionAlthough the numbers are small, elderly patients with DHL can achieve durable EFS and OS. Using the comprehensive geriatric assessment can aid in decision making in the treatment options for elderly patients. Our retrospective analysis, given a small sample size, suggests that intensive treatment regimens can be offered to elderly patients with DHL.

Autologous Stem Cell Transplantation in Elderly Lymphoma Patients in Their 70s: Outcomes and Analysis.

High-dose chemotherapy and autologous stem cell transplantation (ASCT) can offer durable remission in many patients with relapsed or high-risk lymphoma. However, elderly patients are often not considered ASCT candidates based on age alone. A retrospective analysis of patients ≥70 years of age with a diagnosis of Hodgkin or non-Hodgkin lymphoma receiving ASCT between 2000 and 2016 at two partner institutions was performed. Clinical data were extracted from institutional databases and individual medical records. Multivariate analysis was performed to examine the association of clinical variables with transplant outcomes. One hundred seven patients were identified. Median age at transplant was 72 years (range, 70-79). The most common lymphoma subtype was diffuse large B-cell (n = 63, 59%). Median time to neutrophil and platelet engraftment were 10 and 12 days, respectively. With a median follow-up for survivors of 20 months following ASCT (range, 6 months to 13.1 years), estimates for 2-year progression-free survival and overall survival were 58% (95% confidence interval [CI], 48%-67%) and 65% (95% CI, 55%-74%), respectively. Two-year estimate for relapse was 34% (95% CI, 25%-44%) and nonrelapse mortality (NRM) was 7% (95% CI, 3%-14%). Multivariate analysis showed that more recent date of transplant was associated with lower NRM. The Hematopoietic Cell Transplantation-Comorbidity Index score was not predictive of NRM in this data set (high-risk vs. low-risk, hazard ratio 3.45, p = .065). Eligibility for ASCT should be an individualized decision, and age should not be an absolute contraindication to ASCT in healthy elderly patients with lymphoma. Although high-dose chemotherapy and autologous stem cell transplantation (ASCT) can offer durable remission in many patients with relapsed or high-risk lymphoma, elderly patients are often not considered candidates due to concern for excess toxicity and mortality. This retrospective study showed favorable transplant outcomes, including survival and toxicity, in a large cohort of lymphoma patients over 70 years of age who underwent ASCT. Eligibility for ASCT should be an individualized decision, and age should not be an absolute contraindication to ASCT in healthy elderly patients with lymphoma.

Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: an analysis of patients treated on the RICOVER-60 trial

BackgroundThe prognosis of elderly patients with aggressive B-non-Hodgkin’s lymphoma after first lymphoma-related treatment failure (TF-L) is not well described. MethodsWe analysed patient characteristics including the presence of MYC rearrangements and MYC-expression immunohistochemistry (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 and 80 years who had been treated on the RICOVER-60 trial. ResultsTF-L occurred in 301 of the 1222 (24.6%) patients; 297 patients could be analysed. Prognosis was extremely poor in patients with primary progressive disease or early relapse (≤12 months) with median survivals of 3.3 and 6.4 months. Survival after TF-L was significantly lower in patients pretreated with R-CHOP compared with CHOP (23.0% versus 36.4% at 2 years, P = 0.016). In patients with MYC translocation at diagnosis Rituximab reduced the risk of TF-L from 58.8% to 26.3%. Survival after TF-L was significant longer for patients after CHOP without MYC translocations (31.8% versus 0% at 2 years, P < 0.001) or negative MYC-IHC (41.0% versus 16.8% at 2 years, P = 0.017) but not after R-CHOP. 224 patients (75.4%) received salvage therapy. Rituximab was part of salvage therapy in 57.4% and improved 2-year survival rate from 20.7% to 46.8% (P < 0.001). The benefit of R was significant after first-line CHOP [2-year overall survival (OS) 49.6% versus 19.1%, P < 0.001] as well as after R-CHOP (2-year OS 33.1% and 22.5%, P = 0.034). For patients pretreated with R-CHOP long-term survival was below 15% regardless of the treatment chosen. ConclusionMYC rearrangement and IHC are adverse prognostic factors after TF-L for CHOP treated patients, rituximab as part of first-line therapy reduced the effects of MYC-break. Rituximab improves results of any type of salvage therapy; however, survival after progression/relapse of aggressive B-cell lymphoma in elderly patients pretreated with (R)-CHOP is poor regardless of treatment chosen.

Potentially inappropriate medication use in elderly non-Hodgkin lymphoma patients is associated with reduced survival and increased toxicities.

Survival outcomes for elderly lymphoma patients are disproportionally inferior to those of younger patients. We examined medication usage at diagnosis for 171 elderly patients (median age 70years) with aggressive non-Hodgkin lymphoma treated between 2009 and 2014. At least one potentially inappropriate medication was used in 47% of patients according to the Beers Criteria, 59% experienced treatment delays and/or dose reduction and 65% experienced ≥ grade 3 treatment-related toxicities. We report here for the first time that potentially inappropriate medication use was associated with reduced progression-free survival and overall survival, and increased ≥ grade 3 treatment-related toxicities in multivariate analysis.

Autologous stem cell transplantation and stem cell mobilization kinetics in elderly patients with B cell non-Hodgkin lymphoma

As known, the world population is aging and as the life span increases the number of advanced-age lymphomas also shows an upward trend. Autologous hematopoietic stem cell transplantation (HSCT) is the standard treatment modality in chemotherapy-sensitive relapsed or refractory aggressive lymphomas. Increased morbidity and mortality related to both the transplant itself and comorbid diseases can be observed in elderly lymphoma patients. Patients who are 65 years or older and underwent autologous HSCT with B-cell non-Hodgkin lymphoma were retrospectively included in our study. In terms of survival analysis, median follow-up was 34.5 months (8–159) while the overall survival (OS) was 58%. In the univariate analysis of prognostic data in OS, patients who were referred to transplantation with complete response had a statistically significant survival advantage (p=0.043). In terms of the effect of pre-transplant conditioning regimens on survival, BEAM regimen yielded better results, though not statistically significant. Age, number of chemotherapy cycles received before mobilization and radiation therapy had no significant effect on the CD34 (+) cell count in the final product (p=0.492, 0.746 and 0.078 respectively). In conclusion, autologous HSCT is a practicable treatment modality that provides survival advantage in suitable advanced-age patients with a diagnosis of B-cell non-Hodgkin lymphoma.

Model-based optimization of G-CSF treatment during cytotoxic chemotherapy

PurposeAlthough G-CSF is widely used to prevent or ameliorate leukopenia during cytotoxic chemotherapies, its optimal use is still under debate and depends on many therapy parameters such as dosing and timing of cytotoxic drugs and G-CSF, G-CSF pharmaceuticals used and individual risk factors of patients.MethodsWe integrate available biological knowledge and clinical data regarding cell kinetics of bone marrow granulopoiesis, the cytotoxic effects of chemotherapy and pharmacokinetics and pharmacodynamics of G-CSF applications (filgrastim or pegfilgrastim) into a comprehensive model. The model explains leukocyte time courses of more than 70 therapy scenarios comprising 10 different cytotoxic drugs. It is applied to develop optimized G-CSF schedules for a variety of clinical scenarios.ResultsClinical trial results showed validity of model predictions regarding alternative G-CSF schedules. We propose modifications of G-CSF treatment for the chemotherapies ‘BEACOPP escalated’ (Hodgkin’s disease), ‘ETC’ (breast cancer), and risk-adapted schedules for ‘CHOP-14’ (aggressive non-Hodgkin’s lymphoma in elderly patients).ConclusionsWe conclude that we established a model of human granulopoiesis under chemotherapy which allows predictions of yet untested G-CSF schedules, comparisons between them, and optimization of filgrastim and pegfilgrastim treatment. As a general rule of thumb, G-CSF treatment should not be started too early and patients could profit from filgrastim treatment continued until the end of the chemotherapy cycle.

Abstract 5044: Pharmacokinetic study of RCHOP protocol in elderly patients with non-Hodgkin lymphoma

Abstract Background : Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in elderly patients and R-CHOP chemotherapy is the standard treatment protocol for DLBCL. Elderly patients (often defined as 75 years of age) are treated with anticancer drugs with precaution; however, the pharmacokinetics and pharmacodynamics (PK and PD) of these agents have not been thoroughly investigated in this population. In this study we investigated the PK of cyclophosphamide (CP) and doxorubicin (DOX) in elderly patients in order to verify if there is an influence of age on the PK of these anticancer drugs. Methods: Non-Hodgkin lymphoma elderly patients were treated with a R-miniCHOP chemotherapy regimen. Dose levels were 25 mg/m², 0.7-1.4 mg/m², 750 mg/m² and 375 mg/m² for DOX, Vincristin (VCR), CP and Rituximab respectively. For PK analysis, 7 time point samples were collected over 48 h post administraion on cycle 3. CP and VIN plasma concentrations were measured using UPLC-MS/MS validated method. DOX plasma concentrations were measured using UPLC coupled with fluorescence detection validated method. PK-POP modeling has been performed with a non linear mixed effect model program (Monolix version 4.3.2). Results: 31 patients (15 males and 16 females), 75 to 96 years old, were treated with DOX and CYP. Among them, 19 patients have received VCR. A total of 134 and 120 concentrations for DOX and CP were used respectively for PK-POP modeling. A 2-compartment open model adequately described DOX concentration versus time courses. A 1-compartment open model adequately described CP concentration versus time courses. The interindividual variabilities (ISV) could be well estimated for both drugs and for all structural parameters (clearances: CL, Q, volumes of distribution: Vc, Vp) except V for CP. The population PK parameters for DOX obtained for the structural model were: CL=54.5 L/h, Q=54.7 L/h, Vc=30.6 L , Vp= 1140 L. The population PK parameters for CP were: CL=3.49 L/h, Vc=29.2 L. VCR increases DOX Vc from 30.6 L to 56.9L L/h (p =0.0012). The main covariate effects were related to gender, age, BW and to albumin. Conclusions: In this study we have estimated with very good precision PK parameters of DOX and CP in very elderly patients with DLBCL. Our data revealed the effect of gender, BW and VCR administration on DOX PK parameters. We have demonstrated the effect of increasing age on PK of CP. A PK-PD modeling will be performed in order to verify there are biological factors explaining the variation in the PK parameters of DOX and CP in elderly patients. Citation Format: Elodie BAUDRY, Anne Laure COUDREC, Pascal CHAIBI, Fanny BRET, Sara DJEBNOUN, Sophie WEILL, Samuel HUGUET, Alexandre BOYAULT, Francois LOKIEC, Keyvan REZAI. Pharmacokinetic study of RCHOP protocol in elderly patients with non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5044. doi:10.1158/1538-7445.AM2017-5044

Safety and efficacy of autologous stem cell transplantation in lymphoma patients in their 70s.

e19003 Background: High-dose chemotherapy and autologous stem cell transplantation (ASCT) can offer durable remission in many patients with relapsed or high-risk lymphoma. Elderly patients, who make up an increasing proportion of lymphoma patients, are often not considered candidates due to concern for excess toxicity and mortality. However, preliminary reports suggest that ASCT in carefully selected elderly patients can be feasible, safe, and effective. Methods: We identified patients ≥70 years of age with Hodgkin or non-Hodgkin lymphoma who underwent ASCT between 2000 and 2016 at two partner institutions. We recorded clinical characteristics, lymphoma diagnosis, conditioning regimen; and outcomes regarding engraftment, treatment toxicities, and relapse. Kaplan-Meier survival analysis for overall and relapse-free survival was performed. Results: 119 elderly patients with lymphoma who were treated with ASCT were identified. Median age at transplant was 72 (range, 70-79). The most common lymphoma subtype was diffuse large B-cell (n=75, 63%); others were T-cell (n=19), mantle cell (n=12), follicular (n=7), and Hodgkin (n=6). Conditioning regimens included BEAM (BCNU, etoposide, Ara-C, melphalan), CBV (cyclophosphamide, BCNU, etoposide), and Bu/Cy (busulfan/cyclophosphamide). Median time to neutrophil recovery (ANC&gt;500) and platelet recovery (&gt;20,000) were 10 and 12 days, respectively. Three patients had early mortality (within 100 days) from rapid disease progression (n=1) or treatment toxicity (n=2). Median follow up for survivors was 23 months (range, 0-157). Two-year progression-free survival and overall survival were 58% (95%CI, 48-67%) and 66% (95%CI, 55-74%), respectively. The leading cause of treatment failure was disease relapse, which occurred in 33% of patients (n=39). Two-year estimate for non-relapse mortality was 7% (95%CI, 3-14%). Conclusions: ASCT is safe and feasible in selected elderly lymphoma patients, although relapse and non-relapse mortality may be higher than in younger patients. Eligibility for ASCT should be an individualized decision, and age should not be an absolute barrier to ASCT referral in healthy elderly patients with lymphoma.

Predictors of Chemotherapy Related Toxicities in Elderly Lymphoma Patients: Experience from a Tertiary Cancer Centre.

Identification of baseline parameters that predict chemotherapy related morbidities in elderly lymphoma patients can help in tailoring treatment. However, there is a paucity of tools to predict the risk of chemotherapy related toxicity in elderly lymphoma patients from India. We retrospectively analyzed 203 lymphoma patients more than 60years of age for predictors of grade III or higher haematological and non-haematological toxicity due to chemotherapy. Eighty-five (42%) and seventy-one (35%) lymphoma patients developed grade III or IV haematological and non-haematological toxicities respectively. On multivariate analysis baseline absolute lymphocyte counts (ALC) less than 1300/µl, chemotherapy with anthracyclines and presence of two co-morbid conditions were significant in predicting serious haematological toxicities. For non-haematological toxicities baseline ALT levels more than 40U/l was the only significant factor. This is the first report from India on the study of factors predicting serious chemotherapy related adverse effects in elderly lymphoma patients. Patients with low ALC, elevated ALT, multiple co-morbidities and receiving anthracyclines should be closely monitored for chemotherapy related toxicities.

The IVDG Regimen is the Possible Treatment of Choice as First Line Therapy For Hodgkin’s Lymphoma in Elderly Patients with Cardiovascular and Pulmonary Comorbidity

Background. Among the newly diagnosed patients with Hodgkin's lymphoma (HL), the proportion of elderly patients account for 15-35 %. In &gt; 60 age group the choice of antitumor treatment requires an more individualised approach compared to a younger population. The ABVD regimen is acceptable in terms of efficiency and hematological toxicity, but is associated with a high risk of bleomycine-induced pulmonary complications. In &gt; 60 age group the morbitity and mortality of pulmonary complications account for 24 % and 18 %, respectively. Aim. We aimed to evaluate the efficacy of the IVDG regimen in comparison with ABVD by the principle of “non-inferiority”. Materials &amp; Methods. This single centre, prospective, controlled, randomised study was started in 2009. The study included all primary patients aged &gt; 60 years with verified HL, regardless of the number and severity of comorbidities. The ABVD regimen was administered in 17 patients, and 20 patients received IVDG. The median age in the ABVD and IVDG groups was 67 and 70 years, respectively. The advanced stages of HL were reported in 13 (65 %) patients on IVDG, and in 12 (71 %) patients on ABVD (p = 0.9). Both of the groups were comparable in terms of the prevalence of chronic heart failure and chronic obstructive pulmonary disease. The prevalence of ischemic heart disease was higher in the IVDG group (n = 16) compared to ABVD (n = 8) (p = 0.04). Results. IVDG and ABVD groups did not differ in the frequency of complete (14 and 10) and partial (3 and 4) remissions. Differences in 5-year overall survival were insignificant: 49 % in the IVDG group, vs 22 % in ABVD group (p = 0.41). No infectious or hemorrhagic complications were observed in both groups. The incidence of drug-induced pulmonary fibrosis after treatment was significantly lower in the IVDG group (n = 0) vs ABVD group (n = 4; 24 %) (p = 0.004). Conclusion. The IVDG regimen may be used as first line treatment for HL in the elderly patients, especially in those having cardiac or pulmonary comorbidities. Compared to ABVD the IVDG regimen had similar efficacy and more beneficial safety profile in terms of cardiovascular and pulmonary toxicity.

High-Grade Diffuse Large B-Cell Lymphoma in Elderly Patients: Russian Multicenter Trial Results in R-EPOCH/R-HMA Protocol

Background: The number of elderly patients with diffuse large B-cell lymphoma (DLBCL) in our aging society continues to rise. Median of age for patients with diffuse large B-cell lymphoma (DLBCL) is 60. Approximately 50% of older patients with DLBCL are defined as high-grade by IPI and these forms are characterized by aggressive course and poor response to standard chemotherapy (CT). Intensive protocols cannot be performed due to their toxicity for older patients with comorbidity. Addition of R-HMA to R-DA-EPOCH favourably changes the outcome in patients with untreated high-grade diffuse large B-cell lymphoma and didn't have higher toxicity [ASH 2015 # 2708].Aim: To evaluate the efficacy and toxicity of R-EPOCH/R-HMA protocol in older patients with untreated high-grade diffuse large B-cell lymphoma.Patients and Methods: 19 untreated older DLBCL patients from 4 centers were enrolled in a prospective study between August 2013 - July 2016; stage II-IV; ECOG 0-3; median age 66 years (60-78); age ≥70y/60<70y 21%/79%; M/F 52%/48%; IPI: 52% high-intermediate and 48% high risk; 26% with bone marrow involvement. Severe comorbidity was diagnosed in 8 (42%) patients (coronary heart disease, hypertonic disease, chronic obstructive pulmonary disease and arrhythmia). All patients underwent 4-6 courses (2-3 cycles) of chemotherapy: R-EPOCH (standard dose and scheme), R-HMA (R 375 mg/m2 d1, MTX 500 mg/m2 24 hours d 2, AraC 1000 mg/m2 q 12 hrs d 3-4). In 3 cases of DLBCL with bone marrow involvement BEAM conditioning and autologous stem cell transplantation were applied.Results: The median follow-up is 18 months (3-37). There was no mortality associated with toxicity. The main non-hematological toxicities of R-HMA were infections (mucositis, pneumonia, sepsis, enteropathy) grades 1-2 and 3-4 in 90% and 10%, respectively. Hematological toxicity grade 4 for less than 4 days we observed only after courses R-HMA. Complete remission (CR) was achieved in 18 (100%) patients and 1 patient in the treatment now. There are four failures in patients older than 60 years: three relapses (after 6 and two after 14 month CR) and one death after 7 month CR by reasons not related with DLBCL.With a median follow 18 months overall and event-free survival of 19 older patients constituted 93,8% and 75,9%, respectively (Fig.1). There is no difference in older patients according to stage, IPI, LDH level, ECOG status for OS and EFS. So the combination of R-EPOCH/R-HMA may be considered as optimal intensive approach in older patients.Conclusions: TheR-EPOCH/R-HMA protocol demonstrated acceptable toxicity and high efficacy in older patients with high-grade DLBCL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.