ABSTRACT
Background: Non-Hodgkin lymphoma (NHL) is the largest group of hematological malignancies and represented 12% of all new cancer cases in metropolitan France in 2018. The survival outcomes of NHL patients have improved due to important therapeutic advances. Age-standardized 5-year net survival from 2010 to 2015 in France was 86% for follicular lymphoma (FL) and 61% for diffuse large B cell lymphoma (DLBCL), which are above the average survival rates in Europe (FL 72% and DLBCL 51%). In this context, the question of quality of life in NHL patients is garnering increasing interest. To the best of our knowledge, few data from France have addressed the issue of living conditions of long-term NHL survivors at the scale of the general population. Aims: To identify the clinical and social determinants of long-term health related quality of life (HRQoL) in NHL survivors in the general population and to describe their socio-professional reintegration, socio-economic status, sexual wellbeing and the impact of COVID. Methods: All patients were registered in the population-based cancer registry specialized in hematological malignancies in the Côte d'Or area (A French Department with a total of 532,901 residents in 2019). We identified patients diagnosed with DLBCL or FL according to the third edition of the International Classification of Diseases for Oncology (ICD-O- 3), from January 1st 2010 to December, 31st 2017, and who were still alive on March, 1st 2021, with an updated address. Patients under 18 years old and adults unable to provide consent were not eligible. In March 2021, patients completed standardized self-report questionnaires for HRQoL (SF-12), anxiety and depression (HADS), social support (SSQ6), socio-economic deprivation (EPICES). Reminders were sent to non-responders after one month. The determinants of HRQoL were identified using a generalized linear model. Results: Among 436 patients diagnosed, 248 were alive at the study endpoint, of whom 157 (FL 51% and DLBCL 49%) completed the questionnaires, yielding a response rate of 63.3%, the median of time since diagnosis was 76 months [39-133]. The mean age of participants was 67.3 years (SD = 12.4), 55% were men, 74% Ann Arbor stage III-IV, 78% were treated by chemotherapy and immunotherapy, with 99% in the DLBCL group, 11% relapsed after treatment, 64% had no comorbidities and 62% did not have socio-economic deprivation, 27% were employed at the time of the survey, 60% of survivors had not received information about sexuality, 29% reported a negative impact of the disease on their professional activities, 54% reported an impact of the COVID crisis on their life. This impact was socio-economic for 77% and psychological for 23% of respondents. The main factors associated with a negative impact on HRQoL were depression, anxiety, and loss of sexual desire. Summary/Conclusion: Six years after diagnosis, clinical parameters did not have a major influence on HRQoL, except for relapse. The main determinants of HRQoL identified were psychological and social factors. All these elements are potential targets for specific interventions by the social system to improve HRQoL in NHL patients.
ABSTRACT
Introduction: Patients with therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) are a known high-risk AML subgroup with historically poor outcomes. In December 2018, CPX-351 (Vyxeos ® Liposomal) received a positive reimbursement decision in England for the treatment of adults with newly diagnosed t-AML or AML-MRC. The objective of this retrospective study was to utilize the Cancer Analysis System (CAS) database available through the National Cancer Registration and Analysis Service (NCRAS) to describe the demographics, clinical characteristics, and treatment pathways for patients with t-AML or AML-MRC in England from 2013 to 2020, including the use of CPX-351. Methods: The NCRAS systematically collects and curates population-level data about cancer diagnoses, treatments, and outcomes across England. Adults (aged ≥18 years) diagnosed with t-AML or AML-MRC between January 2013 and March 2020 were identified either directly using International Classification of Diseases for Oncology, Third Edition(ICD-O-3) codes or indirectly using non-specific ICD-O-2, ICD-O-3, or ICD-10 AML codes in combination with a record of prior systemic anticancer therapy or radiotherapy (t-AML) or a prior diagnosis of MDS or CMML (AML-MRC;other AML-MRC subtypes could not be distinguished from de novo AML). First-line and second-line treatments identified included clinical trials, intensive chemotherapy (IC) treatments (CPX-351;daunorubicin plus cytarabine [DA];fludarabine, cytarabine, idarubicin and granulocyte-colony stimulating factor [FLAG-Ida];or “other IC” consisting of mitoxantrone-based therapy or high-dose cytarabine alone), or less-intensive therapies (azacitidine, low-dose cytarabine [LDAC], or hydroxycarbamide alone). Patients who did not receive active systemic therapy (ie, those who received best supportive care alone) were not included. Results: A total of 2,891 patients with t-AML or AML-MRC were identified. Most patients were male (62%), white (91%), and aged ≥60 years (80%). Overall, 590 (20%) patients received first-line treatment in a clinical trial, 1,474 (51%) received less-intensive therapy, and 827 (29%) received an IC regimen. Patients aged ≥60 years at diagnosis were less likely than those aged <60 years to either enter a clinical trial (18% vs 32%, respectively) or receive IC (22% vs 54%). In patients treated with IC, those who received CPX-351 were slightly older (mean [standard deviation] age: 63.9 years [8.3]) than those who received DA (60.5 years [11.4]) or FLAG-Ida (55.6 years [12.6]);28% of patients treated with CPX-351 were aged <60 years compared to 37% for DA and 55% for FLAG-Ida. When treatment patterns were analyzed per annum, utilization of less-intensive therapies remained stable over time (Figure 1A). Azacitidine was the most common less-intensive therapy both overall (64%) and across all yearly time points, followed overall by LDAC (22%) then hydroxycarbamide alone (14%). In contrast, the IC treatment patterns were more dynamic over time (Figure 1B). DA chemotherapy was the most common IC overall (48%), followed by FLAG-Ida (23%) and other ICs (18%). However, CPX-351 uptake started in 2018 (5% of all IC) and by the end of 2019 had displaced DA chemotherapy as standard-of-care IC (40% vs 22%, respectively). Excluding patients who were alive but had not received subsequent therapy (ie, censored), most patients who received front-line azacitidine or LDAC died without receiving salvage therapy (89% and 92%, respectively). In comparison, non-censored patients who received front-line DA chemotherapy or FLAG-Ida were more likely to receive salvage treatment (52% and 34%, respectively). Key salvage treatments following DA included azacitidine alone and FLAG-based therapy. Key salvage treatments following front-line CPX-351 included FLAG-Ida or DA ± hematopoietic cell transplant and azacitidine. Conclusions: This large population-level, retrospective analysis of CAS data provides a detailed overview of the management of patients with t-AML and AML-MRC. Historically a high proportion of these high-risk patients have received less-intensive treatment. Since 2018, CPX-351 has been rapidly adopted into the IC treatment pathway, displacing DA chemotherapy. These analyses will be repeated after the CAS database has been updated to determine the impact of COVID-19. [Formula presented] Disclosures: Legg: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Muzwidzwa: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Adamson: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Wilkes: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Medalla: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company.
ABSTRACT
Introduction: CPX-351 (US: Vyxeos ®;Europe: Vyxeos ® Liposomal) is a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio. Since November 2018, the National Institute for Health and Care Excellence (NICE) has recommended its use for adults with newly diagnosed, therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) due to either prior myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML) or de novo AML with myelodysplasia-related cytogenetic changes. The key aims of this study were to utilize the Cancer Analysis System (CAS) database available through the National Cancer Registration and Analysis Service (NCRAS) to describe the demographics and clinical characteristics of adults with AML in England who have received CPX-351, as well as to estimate overall survival (OS) and survival within stratifications of interest. Methods: The NCRAS systematically collects and curates population-level data about cancer diagnoses, treatments, and outcomes across England. Adults (aged ≥18 years) diagnosed with AML and treated with CPX-351 were included in this study. A diagnosis of t-AML or AML-MRC between January 2013 and March 2020 was determined either directly using International Classification of Diseases for Oncology, Third Edition (ICD-O-3) codes or indirectly using non-specific ICD-O-2, ICD-O-3, or ICD-10 AML codes in combination with either prior systemic anticancer therapy or radiotherapy (t-AML) or a prior diagnosis of MDS or CMML (AML-MRC;other AML-MRC subtypes could not be specifically identified and are included within the de novo AML subgroup). OS was measured from the date of diagnosis;a separate analysis of OS landmarked from the date of hematopoietic cell transplant (HCT) was also performed. Within this preliminary analysis, no OS adjustments have been made to account for any COVID-19-related deaths. Results: A total of 172 patients with AML who were treated with CPX-351 were identified: 37 (22%) had t-AML, 57 (33%) had AML-MRC, and 78 (45%) had de novo AML. At diagnosis, the mean (standard deviation) age was 62.8 years (10.1), with 49/172 (28%) patients aged <60 years;66% of patients were male;87% were white;and most had an Eastern Cooperative Oncology Group performance status of 0 or 1 (68%). Six (3%) patients had received azacitidine treatment for a prior malignancy. To date, 43/172 (25%) patients had undergone HCT overall, including 43/97 (44%) patients with ≥3 months of follow-up. The cut-off date for OS was December 31, 2020, giving a median (interquartile range) follow-up of 11.2 months (3.6, 16.9). Overall, 91 patients had died, with an estimated median OS (95% confidence interval [CI]) of 16.6 months (11.0, not estimable) and probability of survival (95% CI) at 1 and 2 years of 0.54 (0.47, 0.62) and 0.39 (0.30, 0.50), respectively (Figure 1). Early mortality rates were 7% at 30 days and 15% at 60 days. When OS was landmarked from the date of HCT, median OS was not reached, with a probability of survival (95% CI) at 1 year of 0.74 (0.62, 0.89;Figure 2). When stratified by age, estimated median OS (95% CI) was not reached for patients aged <60 years and 12.8 months (8.9, 17.6) for patients aged ≥60 years. In a treatment patterns analysis that evaluated second-line treatments after CPX-351, 68 patients died without salvage therapy and 64 were alive without receiving subsequent therapy by the end of the study period. The most common salvage treatments were fludarabine, cytarabine, idarubicin, and granulocyte-colony stimulating factor (FLAG-Ida;n = 15), daunorubicin plus cytarabine (DA)-based therapy (n = 6), and azacitidine alone (n = 7). Of the 43 patients who received an HCT, 6 (14%) underwent HCT following salvage therapy. Conclusions: This is the largest study to date examining the real-world outcomes for patients with AML who were treated with CPX-351. The estimated median OS of 16.6 months is consistent with reported real-world outcomes for CPX-351 in French and Italian studies. Median OS has not been reached in patients aged <60 years or when landmarked from the date of HCT. Once the CAS database has been updated, these analyses will be repeated to increase follow-up and patient numbers and to determine the impact of COVID-19 on OS following CPX-351 treatment. [Formula presented] Disclosures: Legg: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Doubleday: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Reich: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Lambova: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Medalla: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company.