Treatment approaches for older and oldest patients with diffuse large B-cell lymphoma - Use of non-R-CHOP alternative therapies and impact of comorbidities on treatment choices and outcome: A Humedica database retrospective cohort analysis, 2007-2015.

INTRODUCTION: We characterized real-world treatment patterns in older (65-74 years) and oldest (75-85 years) patients with diffuse large B-cell lymphoma (DLBCL) receiving initial therapy (R-CHOP, non-R-CHOP regimens). Impact of comorbidities on treatment choice, and overall and progression-free survival (OS, PFS) were assessed by age. PATIENTS AND METHODS: Using the Humedica database, we identified 1436 newly diagnosed patients with DLBCL who received frontline therapy from 1/07-9/15. The 885 patients ≥65 years of age were further evaluated for baseline demographics, comorbidities, initial therapy, and PFS/OS. RESULTS: Of 885 patients, 406 (45.9%) were age 65-74, and 479 (54.1%) age 75-85, years. First line therapy was R-CHOP (61.8%) or non-R-CHOP (38.2%). Although Charlson Comorbidity Index (CCI) scores were similar at baseline, congestive heart failure and myocardial infarction were more common in those receiving non-R-CHOP regimens. Survival outcomes were superior for those receiving initial R-CHOP, versus non-R-CHOP, therapy (median PFS 53.9 versus 27.8 months; two-year PFS 71.2% versus 51.6%, p < .0001; median OS not reached versus 45 months; two-year OS 81.3% versus 62.9%, p < .0001, respectively). Only 10.4% (R-CHOP) and 12.1% (non-R-CHOP) of patients received second line therapies. Two-year OS by age (65-74, 75-85 years) was 66.4% and 39.1%, respectively with R-CHOP (p = .0045), and 74.3% and 54.5%, respectively with non-R-CHOP (p = .004), therapy. Age ≥ 75 years and CCI of 2+ were associated with shorter OS and PFS. CONCLUSIONS: This study identified real-world first line treatment patterns for older patients with DLBCL. Our findings support the feasibility of administering standard R-CHOP therapy, even to oldest patients with DLBCL.

Evaluation of treatment patterns and survival among patients with diffuse large B-cell lymphoma in the USA.

AIM: To evaluate treatment patterns of diffuse large B-cell lymphoma (DLBCL). PATIENTS & METHODS: First-line and relapsed/refractory treatment patterns and survival outcomes following first-line therapy in adult patients newly diagnosed with DLBCL were evaluated. RESULTS: A total of 1436 DLBCL patients initiated treatment and mainly received a combination regimen versus monotherapy (92.1 vs 7.9%). Patients who received monotherapy were older with more comorbidities and had shorter progression-free survival than patients receiving combination therapy (median: 31.3 vs 55.8 months). In the second-line setting (n = 164), rituximab-based combination regimens were most common; 25% underwent stem cell transplantation, and were younger with fewer comorbidities. CONCLUSION: These results illustrate the need for new treatment options for patients unable to tolerate initial combination therapy and transplant-ineligible patients who require salvage therapy.

Treatment Patterns and Survival Outcomes in Patients With Follicular Lymphoma: A 2007 to 2015 Humedica Database Study.

BACKGROUND: Few studies have evaluated real-world treatment patterns and survival in follicular lymphoma (FL). This study evaluated these outcomes among newly diagnosed patients with FL in routine clinical care. PATIENTS AND METHODS: A retrospective study was conducted in newly diagnosed patients with FL from Humedica, a large United States electronic medical record database, from January 1, 2008 to July 31, 2015. Patients were followed from treatment initiation until death, loss to follow-up, or end of study (September 30, 2015). Treatment patterns were assessed in the follow-up period. Progression-free survival (PFS) and overall survival (OS) at 2 years were evaluated in the overall population using Kaplan-Meier analyses. OS was also compared between patients with and without evidence of disease progression within 2 years following first-line therapy (ie, early progressors vs. non-early progressors). RESULTS: A total of 1346 patients were included in the study, with most patients receiving rituximab-based regimens. Fewer early progressors received rituximab-based regimens. Across all lines, combination therapies predominated, particularly bendamustine + rituximab. Following first-line therapy, OS was 86.9% at 2 years, and median OS was not reached. Two-year PFS after first-line therapy was 64.6%, and median PFS was 48.1 months (95% confidence interval, 39.4-58.4 months). OS at 2 years was 76.8% among early progressors versus 90.4% among non-early progressors (P < .001); the median OS was not reached in both groups. CONCLUSION: In routine clinical practice, rituximab-based regimens predominated; however, utilization of these regimens differed among early and non-early progressors. The assessment of survival outcomes also highlights the negative impact of early progression on OS in the rituximab-era.

Economic burden of patients with diffuse large B-cell and follicular lymphoma treated in the USA.

AIM: Evaluate healthcare costs and utilization of treated diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) patients. MATERIALS & METHODS: Adults with newly diagnosed DLBCL and FL between 1 January 2008 and 31 October 2015 were identified in the Optum™ claims database. Healthcare costs and utilization were assessed from diagnosis date until end of follow-up. RESULTS: A total of 1267 DLBCL- and 1595 FL-treated patients were identified. Mean per-patient, per-month cost during follow-up was US$11,890 for DLBCL and US$10,460 for FL. Healthcare costs and utilization decreased from year 1 to 2 following diagnosis, due to a decrease in chemotherapy services, inpatient admissions and other outpatient services. CONCLUSION: The economic burden of treated DLBCL and FL is considerable, especially in the first year following diagnosis.

The economic burden of end-of-life care in metastatic breast cancer.

OBJECTIVE: To assess end-of-life (EOL) total healthcare costs and resource utilization during the last 6 months of claims follow-up among patients with metastatic breast cancer (MBC) who received systemic anti-neoplastic therapy. METHODS: Newly diagnosed females with MBC initiating treatment January 1, 2003-June 30, 2011 were identified in a large commercial claims database. Two cohorts were defined based on a proxy measure for EOL 1 month prior to the end of last recorded follow-up within the study period: patients who were assumed dead at end of claims follow-up (EOL cohort) and patients who were alive (no-end-of-life [NEOL] cohort). Proxy measures for EOL were obtained from published literature and clinical expert opinion. Cost and resource utilization were evaluated for the 6 months prior to end of claims follow-up. Baseline variables, resource utilization, and costs were compared between cohorts with univariate statistical tests. Adjusted relative risks were calculated for resource utilization measures. A covariate-adjusted generalized linear model evaluated 6-month total healthcare costs. RESULTS: Of the 3,878 females included, 18.5% (n = 718) met the criteria for EOL. Mean observational time (MBC onset to end of claims follow-up) was shorter for the EOL cohort (EOL, 32 months vs NEOL, 35 months; p < 0.001). In adjusted analyses, the EOL cohort had 4.15 times higher 6-month total healthcare costs (EOL, $72,112 vs NEOL, $17,137; p < 0.001). NEOL month-to-month mean total healthcare costs fluctuated between $2336-$3145, while EOL costs increased steadily from $8,956 in the sixth month prior to death to $19,326 in the last month of life. The adjusted relative risk of inpatient, hospice and emergency department utilization was >2 times higher in the EOL cohort (p < 0.001). CONCLUSIONS: Potential EOL presented a greater economic burden in the 6 months prior to death. EOL month-to-month costs increased precipitously in the last 2 months of life and were driven by acute inpatient care.

A phase II study of irinotecan and carboplatin in advanced non-small cell lung cancer with pharmacogenomic analysis: final report.

PURPOSE: We conducted a phase II study of carboplatin and irinotecan in patients with advanced non-small cell lung cancer (NSCLC). In addition, we studied the correlation between certain genotypes of enzymes involved in irinotecan metabolism with efficacy and toxicity. PATIENTS AND METHODS: Patients with stage IIIB, IV, or recurrent NSCLC received a combination of irinotecan and carboplatin every 3 weeks at a dose of 200 mg/m2 and area under the curve of 5. Pharmacogenomic analysis was performed on several genes of interest (ABCB1, CYP3A4*1B, ERCC2, GSTP1, UGT1A1*28, and XRCC1). RESULTS: Forty-two patients enrolled between December 2001 and January 2004. Six patients achieved partial responses (14%), and 19 (45%) had stable disease. The median progression-free survival was 6.9 months. The median overall survival was 11.7 months, with 1-year overall survival of 42%. The most common toxicities were hematologic; grade 3 or 4 neutropenia was experienced by 26 patients (62%) during treatment, and 15 patients (36%) experienced grade 3 or 4 thrombocytopenia. The homozygous UGT1A1*28 (7/7) genotype was associated with grade 4 neutropenia in three of four patients (75%), but only eight out of 30 (27%) with 6/6 or 6/7 genotypes experienced grade 4 neutropenia (p = 0.09). None of the 14 patients with the GSTP1 I105V A/A genotype had a partial response, as opposed to five out of 19 (26%) of those with the G/A or G/G genotypes (p = 0.057). CONCLUSION: The combination of carboplatin and irinotecan is an active combination in NSCLC, with response rates comparable with other platinum-containing doublets. Further studies with irinotecan should incorporate prospective pharmacogenomic analysis to identify markers for response and toxicity.