Assessment of second primary malignancies among treated and untreated patients with chronic lymphocytic leukemia using real-world data from the USA.

Aim: Improved management of chronic lymphocytic leukemia (CLL) has resulted in a growing population of CLL survivors; these patients have a higher risk of developing second primary malignancies (SPMs) versus the general population. This retrospective cohort study aims to assess the timing, frequency, incidence and types of SPMs in treated and untreated patients with CLL in the USA, using the Surveillance, Epidemiology, and End Results (SEER) Medicare database, which links a nationally representative cancer registry with Medicare claims data. Patients & methods: Patients aged ≥66 years with newly diagnosed CLL between 1 January 2010 and 31 December 2016, who were enrolled in Parts A and B of Medicare for ≥12 months pre-diagnosis of CLL were selected from the database. Patients were assessed for ≥36 months until the end of continuous enrollment in Medicare Parts A, B and D, a switch to a health maintenance organization, death, or end of the study period (December 2019). Results: Of 3053 patients included in the analyses, 620 (20.3%) were treated and 2433 (79.7%) were untreated within 36 months of diagnosis. Overall, 638 (20.9%) patients developed a SPM, 26.8% of patients in the treated cohort and 19.4% of patients in the untreated cohort. The most common SPMs for both cohorts were squamous cell carcinoma and acute myeloid leukemia. Among the 166 treated patients who developed a SPM, a greater proportion developed their first SPM after treatment initiation versus those who developed their first SPM prior to treatment initiation (p < 0.001). A significantly lower percentage of patients who received targeted therapy developed a SPM (p < 0.05) versus patients treated with anti-CD20 + chemotherapy. Conclusion: Findings indicate that treatment type and timing can affect SPM development in patients with CLL. Combined with previous findings, this can help inform best practices in monitoring for SPM in patients with CLL.

US cost-effectiveness analysis of polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma.

AIMS: We evaluated the pharmacoeconomic value of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) in previously untreated diffuse large B-cell lymphoma (DLBCL) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MATERIALS AND METHODS: A 3-state partitioned survival model was used to estimate life years (LYs), quality-adjusted LYs (QALYs), and cost impacts of Pola-R-CHP versus R-CHOP. Analyses utilized mixture-cure survival modelling, assessed a lifetime horizon, discounted all outcomes at 3% per year, and examined both payer and societal perspectives. Progression-free survival, overall survival (OS), drug utilization, treatment duration, adverse reactions, and subsequent treatment inputs were based on data from the POLARIX study (NCT03274492). Costs included drug acquisition/administration, adverse reaction management, routine care, subsequent treatments, end-of-life care, and work productivity. RESULTS: Incremental cost-effectiveness ratios of Pola-R-CHP versus R-CHOP were $70,719/QALY gained and $88,855/QALY gained from societal and payer perspectives, respectively. The $32,824 higher total cost of Pola-R-CHP versus R-CHOP was largely due to higher drug costs ($122,525 vs $27,694), with cost offsets including subsequent treatment (-$52,765), routine care (-$1,781), end-of-life care (-$383), and work productivity (-$8,418). Pola-R-CHP resulted in an increase of 0.47 LYs and 0.46 QALYs versus R-CHOP. Pola-R-CHP was cost-effective in 60.9% and 58.0% of simulations at a willingness-to-pay threshold of $150,000/QALY gained from societal and payer perspectives, respectively. LIMITATIONS: There was uncertainty around the OS extrapolation in the model, and costs were derived from different sources. Recommended prophylactic medications were not included; prophylactic use of granulocyte colony-stimulating factor for all patients was assumed to be equal across treatment arms in POLARIX. Work productivity loss was estimated from a general population and was not specific to patients with DLBCL. CONCLUSION: Pola-R-CHP was projected to be cost-effective versus R-CHOP in previously untreated DLBCL, suggesting that Pola-R-CHP represents good value relative to R-CHOP in this setting.

Cost of Disease Progression in Diffuse Large B-Cell Lymphoma After Frontline Treatment With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone.

BACKGROUND: In recent years, novel agents have become available to treat relapsed/refractory diffuse large B-cell lymphoma (DLBCL); the impact of such agents on treatment costs has not been formally studied. We present results from 2 independent, retrospective, real-world cohort analyses to determine the cost of disease progression after first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MATERIALS AND METHODS: Analyses were conducted using the IQVIA PharMetricsⓇ Plus claims database and the Surveillance, Epidemiology, and End Results registry-Medicare-linked database (SEER-Medicare) and included patients ≥18 years and ≥66 years, respectively. "No progression" was defined as no second-line therapy for ≥2 years after the end of first-line R-CHOP and "treated progression" as initiating a second-line therapy within 2 years following the end of first-line R-CHOP. Analyses were adjusted for baseline covariates, and per-patient-per-month (PPPM) costs were compared between progressors and nonprogressors. RESULTS: The IQVIA PharMetrics Plus analysis (January 1, 2010-June 30, 2018) included 871 patients (nonprogressors, n = 725; progressors, n = 146), including 10 patients who received chimeric antigen receptor T-cell therapy (CAR-T). Treated progression was associated with significantly higher adjusted PPPM costs than no progression ($10,554 vs. $1561, P < .001). The SEER-Medicare analysis (January 1, 2010-December 31, 2017) included 4099 patients (nonprogressors, n = 3389; progressors, n = 710), including 12 patients receiving CAR-T. Treated progression was associated with significantly higher adjusted PPPM costs than no progression ($10,928 vs. $2902, P < .001). CONCLUSION: Treated progression of DLBCL increases adjusted PPPM costs by over $8000 compared with no progression.

Economic Burden of Recurrence Among Resected Medicare Patients With Early Stage NSCLC.

Introduction: Patients with early NSCLC (eNSCLC) who experience recurrence are associated with worse survival outcomes, but the economic burden of recurrence is not well characterized. This study evaluated the incremental health care resource utilization and costs of recurrence in Medicare patients with resected eNSCLC. Methods: This retrospective observational study used Surveillance, Epidemiology, and End Results cancer registry data linked with Medicare claims. Eligible patients were 65 years and older with newly diagnosed NSCLC stages IB to IIIA (American Joint Committee on Cancer Staging Manual, seventh edition) and surgery between January 2010 and December 2017. Continuous enrollment criteria were applied to ensure appropriate data capture. Per patient per month (PPPM) health care resource utilization and all-cause direct costs were compared for patients with versus without recurrence, which was identified from claims data using diagnosis, procedure, or drug codes. Patients were matched (1:1) using exact matching on cancer stage and treatment, and propensity score matching on other characteristics. Results: In total, 2035 (44%) out of 4595 patients had evidence of recurrence. After matching, 1494 patients were included in each cohort. Patients with recurrence had a significantly higher number of inpatient visits (+0.25 PPPM), outpatient visits (+1.10 PPPM), physician services (+3.70 PPPM), and emergency department (ED) visits (+0.25 PPPM; all p < 0.001). The average follow-up PPPM cost in the recurrence cohort was U.S. dollars $7437 and $1118 in the no-recurrence cohort, resulting in a difference of $6319 PPPM (p < 0.001) with inpatient costs as the largest contributor. Conclusions: On the basis of a real-world population, the recurrence among patients with resected eNSCLC is associated with increased health care resource utilization and costs.

Real-world adjuvant chemotherapy patterns and outcomes among elderly patients with resected early non-small-cell lung cancer in the USA.

Background: This study investigated real-world treatment patterns and overall survival (OS) in early non-small-cell lung cancer patients and the association between OS and time-to-adjuvant-treatment. Materials & methods: This retrospective study using Surveillance, Epidemiology and End Results data linked with Medicare claims included resected early non-small-cell lung cancer patients between 2010 and 2015. Unadjusted OS analyses used Kaplan-Meier curves; adjusted OS analyses used extended Cox proportional hazards models. Results: Only 54-71% of stage II-IIIA patients received any adjuvant treatment. Adjusted risk of death was higher when starting treatment outside 6-8 weeks after surgery (p < 0.05). Conclusion: Improved systemic therapy in the adjuvant chemotherapy setting is needed.

Lung cancer is one of the deadliest cancers in the USA. Most lung cancers are a type called non-small-cell lung cancer (NSCLC). Patients with NSCLC that has not spread to other parts of the body generally have surgery and may receive treatment before surgery, after surgery or both to help fight the cancer. It is not clear how often people receive treatment before or after surgery. It is important to know how patients are being treated because it helps clinicians decide how to use the new treatments that are becoming available. This study used a large database of more than 7000 people aged 65 years and older with lung cancer in the USA to understand how they are treated. More than a third of patients had stage IA NSCLC (39%), followed by stage IB (24%), stage II (20%), stage IIIA (15%) and stage IIIB (2%). Most people had surgery (64%) and some received another treatment after surgery (27%). That treatment was most often about 2 months of chemotherapy, on average. The study also tried to understand how the timing of treatment may have been important for their survival. People who received treatment after surgery lived the longest if they received that treatment about 6­8 weeks after the surgery. Overall, the study showed that a substantial proportion of people do not receive treatment for their NSCLC after surgery, even though treatment after surgery is recommended by medical guidelines. There is a need for more effective treatments for these patients, and when those treatments are given may be important for their survival.

Association of Pneumococcal Conjugate Vaccine Use With Hospitalized Pneumonia in Medicare Beneficiaries 65 Years or Older With and Without Medical Conditions, 2014 to 2017.

Importance: The association of 13-valent pneumococcal conjugate vaccine (PCV13) use with pneumonia hospitalization in older adults, especially those with underlying medical conditions, is not well described. Objective: To evaluate the association of PCV13 use with pneumonia, non-health care-associated (non-HA) pneumonia, and lobar pneumonia (LP) hospitalization among US Medicare beneficiaries 65 years or older. Design, Setting, and Participants: This cohort study with time-varying exposure assignment analyzed claims data from US Medicare beneficiaries 65 years or older enrolled in Parts A/B with a residence in the 50 US states or the District of Columbia by September 1, 2014. New Medicare Parts A/B beneficiaries within 6 months after their 65th birthday were continuously included in the cohort after September 1, 2014, and followed through December 31, 2017. Participants were censored if they died, changed enrollment status, or developed a study outcome. Most of the analyses were conducted from 2018 to 2019, and additional analyses were performed from 2021 to 2022. Exposures: Use of PCV13 vaccination 14 days or more before pneumonia hospitalization. Main Outcomes and Measures: Discrete-time survival models were used to estimate the incidence rate ratio (IRR) and number of pneumonia hospitalizations averted through PCV13 use. The adjusted IRR for the association of PCV13 vaccination with pneumonia hospitalization was used to estimate vaccine effectiveness (VE). Results: At the end of follow-up (December 2017), 24 121 625 beneficiaries (13 593 975 women [56.4%]; 418 005 [1.7%] Asian, 1 750 807 [4.8%] Black, 338 044 [1.4%] Hispanic, 111 508 [0.5%] Native American, and 20 700 948 [85.8%] White individuals) were in the cohort; 4 936 185 (20.5%) had received PCV13 only, and 10 646 220 (79.5%) had not received any pneumococcal vaccines. More than half of the beneficiaries in the cohort were younger than 75 years, White, and had either immunocompromising or chronic medical conditions. Coverage with PCV13 increased from 0.8% (September 2014) to 41.5% (December 2017). The VE for PCV13 was estimated at 6.7% (95% CI, 5.9%-7.5%) for pneumonia, 4.7% (95% CI, 3.9%-5.6%) for non-HA pneumonia, and 5.8% (95% CI, 2.6%-8.9%) for LP. From September 2014 through December 2017, an estimated 35 127 pneumonia (95% CI, 33 011-37 270), 24 643 non-HA pneumonia (95% CI, 22 761-26 552), and 1294 LP (95% CI, 797-1819) hospitalizations were averted through PCV13 use. Conclusions and Relevance: The study results suggest that PCV13 use was associated with reduced pneumonia hospitalization among Medicare beneficiaries 65 years or older, many of whom had underlying medical conditions. Increased PCV13 coverage and use of recently approved higher-valent pneumococcal conjugate vaccines may avert additional pneumonia hospitalizations in adults.

Idelalisib for Treatment of Relapsed Follicular Lymphoma and Chronic Lymphocytic Leukemia: A Comparison of Treatment Outcomes in Clinical Trial Participants vs Medicare Beneficiaries.

Importance: Idelalisib (IDEL) is approved as monotherapy in relapsed follicular lymphoma (FL) and with rituximab (IDEL+R) for relapsed chronic lymphocytic leukemia (CLL). Toxic effects can be severe and treatment-limiting. Outcomes in a real-world population are not yet characterized. Objective: We compared IDEL treatment outcomes in the clinical setting with outcomes in clinical trial data. Design, Setting, and Participants: This cohort study compared clinical trial participants treated with IDEL, aged 65 years or older, in studies 101-09 and 312-0116 with Medicare beneficiaries treated with IDEL of the same disease state and treatment regimen. Study 101-09 was a phase 2, single-group, open-label trial supporting accelerated approval of IDEL for relapsed or refractory FL. Study 312-0116 was a phase 3, multicenter, randomized, double-blind trial supporting approval of IDEL+R for relapsed CLL. Analyses were conducted between February and December 2018. Main Outcomes and Measures: Treatment duration, on-treatment and overall mortality, and serious and fatal infections were compared between trial participants and Medicare beneficiaries. Cox proportional hazards models quantified differences by cohort. Results: We identified 26 trial participants (mean [SD] age, 73 [4.9] years; 12 [46.2%] women) and 305 Medicare beneficiaries (mean [SD] age, 76 [6.9] years; 103 [54.8%] women) receiving IDEL for FL and 89 trial participants (mean [SD] age, 74 [6.0] years; 30 [33.7%] women) and 294 Medicare beneficiaries (mean age, 76 [6.3] years; 111 [37.8%] women) receiving IDEL+R for CLL. Medicare beneficiaries were older with higher comorbidity; had a shorter median treatment duration for CLL (173 days vs 473 days, P < .001) but not FL (114, days vs 160 days, P = .38); a numerically higher mortality rate (CLL: HR, 1.40; 95% CI, 0.93-2.11; FL: HR, 1.39; 95% CI, 0.69-2.78); and a significantly higher fatal infection rate per 100 person-years for CLL (18.4 vs 9.8, P = .04) and a numerically higher rate for FL (27.6 vs 18.6, P = .54), compared with trial participants. Trial participants had approximately twice as many dose reductions (CLL: 32.6% vs 18.0%; P = .003; FL: 38.5% vs 16.1%; P = .02). Among Medicare beneficiaries, a hospitalized infection within 6 months prior to IDEL initiation was associated with a 2.11-fold increased risk for on-treatment fatal infections (95% CI, 1.44-3.10). Despite a March 2016 recommendation for Pneumocystis jirovecii pneumonia prophylaxis in patients treated with IDEL, prophylaxis rates were low after March 2016 (FL: 25%, CLL: 37%). Conclusions and Relevance: We observed substantial imbalances in baseline comorbidities and treatment outcomes between Medicare beneficiaries and trial participants aged 65 years or older. Immunosuppression-related toxic effects, including infections, may have been somewhat reduced in trials by more frequent dose reductions and exclusion of patients with ongoing infections. Selective eligibility criteria and closer monitoring of trial patients may be responsible for limited generalizability of trial data to clinical practice.

Transition from control to elimination: impact of the 10-year global fund project on malaria control and elimination in China.

The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) supported a project on the control and elimination of malaria in People's Republic of China which was one of the biggest-scale international cooperation programmes to control malaria in the country during the past 10 years. The project promoted the effective implementation of the Chinese national malaria control programme. On the basis of epidemiologic data, an overview of the project activities and key performance indicators, the overall impact of the GFATM project was evaluated. We also reviewed relevant programme features including technological and management approaches, with a focus on best practice, innovations in implementation and the introduction of international standards. Last, we summarised the multi-stakeholder cooperation mechanism and comments on its sustainability in the post-GFATM period. Recommendations for the future management of the Chinese national malaria elimination programme are put forward after considering the challenges, shortcomings and lessons learnt during the implementation of the GFATM project in China to sustain past achievements and foster the attainment of the ultimate goal of malaria elimination for the country.