ALBERT

Description: Introduction: Myelofibrosis (MF) is a rare and progressive myeloproliferative neoplasm (MPN), with increased risk of death due to disease complications and progression. The only curative therapy, bone marrow transplantation, is rarely feasible due to patients' age and comorbidities. Genetic study for prognostication and JAK inhibitors drugs are not available for all patients. Thus, patients with MF, especially those with poor prognosis (int-2 and high-risk IPSS), present decreased quality of life and survival. In Brazil, there is a lack of information regarding the epidemiology and management of the disease. Aims and methods: An expert panel was conducted in June 2019 with seven hematologists from different centers to identify limitations to MF care in Brazil and address pertinent recommendations. The experts received the questions in advance, conducted a literature review, and then discussed results and proposals for MF management in Brazil. Results: Diagnosis of MF, including hematologic, morphologic, and molecular findings, is challenging. In Brazil, patients are often diagnosed in advanced phases of MF what may suggest a late referral for specialized centers. The specialists concluded that awareness about the clinical findings of MF requires attention. An effort also needs to be made regarding morphological diagnosis according to the WHO revised criteria for MPN differential diagnosis. Although the mutational profile is essential for diagnosis and risk stratification, in Brazil, most of the centers have no access to driver mutations tests. The risk stratification relies on clinical scores such as IPSS or DIPSS, which leads to a lower identification of patients with a higher risk of disease that should be considered for transplantation. Regarding the quality of life, there is a sense of low perception about symptomatic severity of patients and physicians. Symptomatic scores, not yet available in Portuguese, are not applied routinely: patients have difficulties in understanding the questions without supervision. Finally, even though the Brazilian public healthcare system is based on the principles of universal coverage, the integrality of care and equity, most patients have limited access to drugs that improve symptoms and survival, like the JAK1/2 inhibitor ruxolitinib. Availability of medications is greater in the private system. However, there is a mandatory list of drugs approved by the insurance companies and updated every two years. Thus, new drugs are not readily available even in this setting. Of note, the majority of the Brazilian population is covered by the public system, while the private system covers 24% of the entire population. Therefore, disparities in health care between public and private systems can affect MF assistance. Based on these findings, the expert panel made the following suggestions: 1) A Brazilian registry, with a representative coverage of the national territory, to better understand the MF patient journey. 2) In order to improve diagnosis, investment in hematopathologist training and molecular testing for JAK2, CALR, and MLP mutations should be encouraged. 3) New prognostic classifications, such as MIPSS70+ version 2.0, that combine genetic and clinical variables, reinforce the need for adopting molecular tests as routine risk assessment. 4) Urgent need to develop a specific instrument to assess the impact of symptoms on the quality of life. Therefore, translation and validation of MPN-SAF TSS have been recently accomplished and will be used by MF reference centers when published. 5) Lack of equity in access to treatment options between public and private system was a consensus among experts. Measures that could address this issue include the establishment of MPN reference centers according to geographic distribution and centralization of the drugs purchasing system. A recently elaborated guideline endorsed by the Brazilian Society of Hematology is being used to circumvent the lack of a national protocol. In conclusion, the identification of limiting factors for MF management leads us to propose recommendations for the Brazilian healthcare system in an attempt to improve patient care. Urgent actions should be taken to improve the unmet needs for these patients, especially in the public system where diagnostic, prognostic, and therapeutic approaches deserve special attention. Disclosures Solza: Novartis: Honoraria. Apa:Novartis: Honoraria. Magalhaes:Novartis: Honoraria. Delamain:Novartis: Honoraria. Tavares:Novartis: Honoraria. Figueiredo-Pontes:Novartis: Honoraria.

Description: Background: Acalabrutinib is a highly selective, covalent irreversible Bruton tyrosine kinase inhibitor with minimal activity against other kinases. Acalabrutinib has demonstrated durable responses as a single agent or combined with O in treatment-naïve (TN) CLL. Here, interim results are presented for the multicenter, open-label Phase 3 ELEVATE-TN study (NCT02475681), which evaluated the efficacy and safety of acalabrutinib + O vs acalabrutinib alone vs O + Clb in pts with TN CLL. Methods: Eligible pts had TN CLL requiring treatment per iwCLL criteria and were aged ≥65 y or 6, creatinine clearance

Description: Quantitative RT-PCR (RQ-PCR) is an essential test for BCR-ABL transcripts monitoring in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKI), to guide therapy and for monitoring after a discontinuation attempt in patients with deep molecular response. RT-PCR (RQ-PCR) is currently not reimbursed by the public health system in Brazil. Aims: To assess the proportion of CML patients treated with first-line imatinib eligible for discontinuation, and to calculate the financial impact resulting from IM discontinuation. Methods: Between January 2010 and December 2011, 151 consecutive cases of chronic phase myeloid leukemia treated with Glivec first-line therapy were evaluated. Between June and December 2013 there was a switch in treatment from Glivec to generic IM. Cases that exhibited stable MR4.5 for 2 years with first-line IM were selected for the study. Cases which switched treatment to second-generation inhibitors and patients older than 75 years of age were excluded from the study. The methodology used was a pharmacoeconomic cost-utility analysis. Glivec monthly cost has been estimated at U$ 3,257.54 and the generic IM U$ 365.48, while the unitary value for the PCR test was U$ 117.49. In order to calculate the period of IM consumption, the median age of the patients and the life expectancy data released in 2015 by the Brazilian Institute of Geography and Statistics (IBGE) of 75 years was considered. In the first analysis, the life expectancy for the sample group, and the total cost of treatment (cost of Glivec, generic IM and four annual RQ-PCR tests for each patient) were calculated. The second analysis consisted of a hypothetical calculation of costs under the scenario where the study group is therapy-free (estimating that the survival rate under discontinued therapy was similar to data available in the literature, with discontinuation success of 50% in this group) with molecular monitoring by PCR monthly in the first year, bimestrial in the second year and every three months from the third year on. Results: One hundred fifty-one cases were analyzed, with a median age at diagnosis of 45. From those, 56 (37%) patients achieved stable MR4.5 with a median time to achieve MR4.5 of 71 months. The median duration of follow-up was 8 (0-10) years. In the last follow-up, 108 patients were still in treatment, 10% (11/108) with Glivec, 90% (97/108) on generic IM. Patients excluded from the analysis: 4 cases aged more than 75 years; 13 that switched therapy to another TKI and one during the bone marrow transplant period. Finally, 38/56 (25%) patients who obtained MR4.5 with IM were eligible for analysis. Analysis 1: Total treatment cost for the 38 eligible cases, if the individuals sustained continuous use of IM, considering the life expectancy of 75 years. The calculations resulted in an average of 29 years of treatment, with an estimated cost of U$ 9,363,866.00. Analysis 2: The cost after discontinuation of generic IM, estimating that 50% of patients would resume the treatment. Nineteen cases were analyzed. The costs related to the monthly PCR exam in year 1, bimestrial exam in year 2 and trimester in year 3, until the patient reaches 75 years of age, have been calculated, with a total cost of U$ 7,823.515. Conclusions: The economy resulting from the discontinuation of treatment (US$1.540.340,00) by 19 patients could support 219 patients tests over 29 years, or 12.110 tests each year. This data is relevant, providing that RQ-PCR is essential for the appropriate management of CML and to allow safe discontinuation of the therapy in eligible patients. Such results may help to change the current health policies concerning RQ-PCR tests reimbursement for CML management and future attempting of TFR in Brazil. Disclosures Centrone: Novartis: Honoraria; Janssen: Honoraria. Magalhaes:Novartis: Honoraria. Pagnano:Pint Pharma: Consultancy; Abbvie: Consultancy; Sandoz: Consultancy.