Cost-Effectiveness Analysis of Venetoclax in Combination with Azacitidine Versus Azacitidine Monotherapy in Patients with Acute Myeloid Leukemia Who are Ineligible for Intensive Chemotherapy: From a US Third Party Payer Perspective.

OBJECTIVES: Using individual patient-level data from the phase 3 VIALE-A trial, this study assessed the cost-effectiveness of venetoclax in combination with azacitidine compared with azacitidine monotherapy for patients newly diagnosed with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy, from a United States (US) third-party payer perspective. METHODS: A partitioned survival model with a 28-day cycle and three health states (event-free survival (EFS), progressive/relapsed disease, and death) was developed to estimate costs and effectiveness of venetoclax + azacitidine versus azacitidine over a lifetime (25-year) horizon. Efficacy inputs (overall survival (OS), EFS, and complete remission (CR)/CR with incomplete marrow recovery (CRi) rate) were estimated using VIALE-A data. Best-fit parametric models per Akaike Information Criterion were used to extrapolate OS until reaching EFS and extrapolate EFS until Year 5. Within EFS, the time spent in CR/CRi was estimated by applying the CR/CRi rate to the EFS curve. Past Year 5, patients still in EFS were considered cured and to have the same mortality as the US general population. Mean time on treatment (ToT) for both regimens was based on the time observed in VIALE-A. Costs of drug acquisition, drug administration (initial and subsequent treatments), subsequent stem cell transplant procedures, adverse events (AEs), and healthcare resource utilization (HRU) associated with health states were obtained from the literature/public data and inflated to 2021 US dollars. Health state utilities were estimated using EuroQol-5 dimension-5 level data from VIALE-A; AE disutilities were obtained from the literature. Incremental cost-effectiveness ratios (ICERs) per life-year (LY) and quality-adjusted life-year (QALY) gained were estimated. Deterministic sensitivity analyses (DSA), scenario analyses, and probabilistic sensitivity analyses (PSA) were also performed. RESULTS: Over a lifetime horizon, venetoclax + azacitidine versus azacitidine led to gains of 1.89 LYs (2.99 vs. 1.10, respectively) and 1.45 QALYs (2.30 vs. 0.84, respectively). Patients receiving venetoclax + azacitidine incurred higher total lifetime costs ($250,486 vs. $110,034 (azacitidine)). The ICERs for venetoclax + azacitidine versus azacitidine were estimated at $74,141 per LY and $96,579 per QALY gained. Results from the DSA and scenario analyses supported the base-case findings, with ICERs ranging from $60,718 to $138,554 per QALY gained. The results were most sensitive to varying the parameters for the venetoclax + azacitidine base-case EFS parametric function (Gompertz), followed by alternative approaches for ToT estimation, treatment costs of venetoclax + azacitidine, standard mortality rate value and ToT estimation, alternative sources to inform HRU, different cure modeling assumptions, and the parameters for the venetoclax + azacitidine base-case OS parametric function (log-normal). Results from the PSA showed that, compared with azacitidine, venetoclax + azacitidine was cost-effective in 99.9% of cases at a willingness-to-pay threshold of $150,000 per QALY. CONCLUSIONS: This analysis suggests that venetoclax + azacitidine offers a cost-effective strategy in the treatment of patients with newly diagnosed AML who are ineligible for intensive chemotherapy from a US third-party payer perspective. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02993523. Date of registration: 15 December 2016.

Successful treatment of relapsed lymphomatoid granulomatosis with bexarotene.

Lymphomatoid granulomatosis is a rare lymphoproliferative disorder involving the lungs, skin and other organs. Advanced-stage disease does not tend to respond well to cytotoxic chemotherapy and is associated with a poor prognosis. We present a case of successful treatment of relapsed lymphomatoid granulomatosis with bexarotene, a novel retinoid agent.

Primary cardiac lymphoma: utility of multimodality imaging in diagnosis and management.

Primary cardiac lymphoma (PCL) is an extremely rare disease defined as a lymphoma strictly confined to the heart or pericardium without dissemination. We present the case of an 82 yr old male with newly diagnosed PCL and two years of subsequent follow up. This report highlights the utility of a multimodality imaging approach in the diagnosis and management of PCL.

Regression of advanced non-splenic marginal zone lymphoma after treatment of hepatitis C virus infection.

We describe a patient with chronic hepatitis C virus (HCV) infection who presented with extranodal (right salivary gland and bone marrow) marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). Within a year, the lymphoma progressed to involve peripheral lymph nodes and the liver. After treatment of HCV with peginterferon and ribavirin, he achieved complete radiographic response and remains in remission two years later. This is an example of a patient in whom treatment of HCV infection led to regression of non-splenic, extranodal marginal zone lymphoma. It suggests that HCV testing and treatment should be considered in all patients with marginal zone lymphomas, including non-splenic types.

Regression of pulmonary MALT lymphoma after treatment with rituximab.

We describe a patient with extranodal (pulmonary) marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) who was refractory to treatment with cytotoxic chemotherapy. After a single four-week course of rituximab she had significant regression of pulmonary lesions and remains progression free 19 months after finishing her treatment. This case report demonstrates the potential efficacy of rituximab as a single therapeutic agent in patients with pulmonary MALT lymphoma.

Enhanced marrow [18F]fluorodeoxyglucose uptake related to myeloid hyperplasia in Hodgkin's lymphoma can simulate lymphoma involvement in marrow.

[18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) is increasingly used for the clinical staging of lymphomas and for assessment of response to therapy. We report the case of a woman with classic Hodgkin's lymphoma who had marked FDG uptake by tumor and bone marrow suggestive of diffuse marrow involvement by lymphoma. However, iliac crest bone marrow examination showed marked myeloid hyperplasia without evidence of lymphoma involvement. We discuss the implications for interpretation of FDG-PET imaging of bone marrow in lymphomas.

Use of iodine 131I-tositumomab radioimmunotherapy in a patient with Waldenstrom's macroglobulinemia.

Waldenstrom's macroglobulinemia is an indolent B-cell malignancy that is characterized by high levels of IgM paraprotein production and is incurable with standard chemotherapy. Iodine 131I-Tositumomab (iodine-131-labeled murine anti-CD20 monoclonal antibody; Bexxar) is a novel radioimmunotherapeutic agent that has a high response rate in relapsed or chemotherapy refractory, CD20-positive, low grade or transformed B-cell non-Hodgkin's lymphomas. There are no data on the use of radioimmunotherapy in Waldenstrom's macroglobulinemia. We report a patient with Waldenstrom's macroglobulinemia with transformation to a large B-cell lymphoma, who was treated successfully with iodine 131I-tositumomab. The patient had a complete response to the treatment, including disappearance of any detectable IgM paraprotein. This case report demonstrates the potential for radioimmunotherapy in CD20 positive B-cell malignancies.

Utility of FDG-PET scanning in lymphoma by WHO classification.

We retrospectively evaluated (18)fluoro-2-deoxyglucose positron emission tomography (FDG-PET) scans in 172 patients with lymphoma and correlated results with pathologic diagnosis using the World Health Organization (WHO) classification system. In total, FDG-PET detected disease in at least one site in 161 patients (94%) and failed to detect disease in 11 patients (6%). The most frequent lymphoma diagnoses were diffuse large B-cell lymphoma (LBCL; n = 51), Hodgkin lymphoma (HL; n = 47), follicular lymphoma (FL; n = 42), marginal zone lymphoma (MZL; n = 12), mantle cell lymphoma (MCL; n = 7), and peripheral T-cell lymphoma (PTCL; n = 5). FDG-PET detected disease in 100% of patients with LBCL and MCL and in 98% of patients with HL and FL. In contrast, FDG-PET detected disease in only 67% of MZL and 40% of PTCL. Comparison with bone marrow biopsies showed that FDG-PET was not reliable for detection of bone marrow involvement in any lymphoma subtype.