ALBERT

Description: Introduction: Patients (pts) with relapsed/refractory PMBCL (rrPMBCL) are typically treated like those with diffuse large B cell lymphoma (DLBCL), often with limited effective treatment options and poor outcomes. Unlike DLBCL and similar to classical Hodgkin lymphoma, PMBCL has frequent genetic abnormalities leading to over-expression of the programmed death (PD)-1 ligands, PD-L1 and PD-L2. This suggests that rrPMBCL should be sensitive to PD-1 blockade. In the phase 1b KEYNOTE (KN)-013 study (NCT01953692), pembrolizumab was associated with frequent and durable responses (Zinzani, Blood 2017) in pts with rrPMBCL. The international phase 2 KN170 (NCT02576990) study was conducted to extend these findings and evaluate correlative biomarkers of response. Here, we present updated results of all pts in KN013 (n=21) and the first full analysis of pts in KN170 (n=53). Methods: KN013 enrolled pts with rrPMBCL who had failed, were ineligible for, or refused autologous stem cell transplant (ASCT). KN170 enrolled pts with rrPMBCL who had relapsed after or were ineligible for ASCT with ≥2 lines of prior therapy. In KN013, the initial 10 pts received pembrolizumab 10 mg/kg Q2W; the remaining 11 patients and all patients on KN170 received pembrolizumab 200 mg Q3W for up to 2 years. Archival or fresh tumor tissue obtained before pembrolizumab initiation was used for correlative studies. Tumor response was assessed with PET/CT scans by IWG 2007 criteria. The primary endpoint of KN170 was objective response rate (ORR) by blinded independent central review (BICR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety/tolerability. Exploratory endpoints included response by Lugano 2014 criteria and biomarker analyses. Data cutoff dates for this analysis were Apr 4, 2018 for KN013 and April 13, 2018 for KN170. Results: KN013 enrolled 21 pts with a median of 3 prior lines of therapy, of whom 13 (62%) were ASCT-ineligible. KN170 enrolled 53 pts also with a median of 3 prior lines, of whom 39 (74%) were ASCT-ineligible due to chemorefractoriness. In KN013, ORR was 48% (10/21; 95% CI, 26-70), with a CR rate of 33% (7/21). In KN170, ORR was 45% (24/53; 95%CI, 32-60), with a CR rate of 13% (7/53; 11/53 [21% by Lugano criteria]). In KN013, after a median follow-up duration of 29.1 mo (range, 0.6-49.6), median DOR was not reached (range, 1.9+ to 39.8+ mo) (Panel A). 2 patients in KN013 in CR at 2 years remained in CR after a further 12 and 18 mo of follow-up off therapy. After a median follow-up of 12.5 mo for KN170 (range, 0.1-25.6), median DOR was not reached (range, 1.1+ to 22.0+ mo) (Panel A). At data cutoff, no patient who achieved a CR on KN170 had relapsed. In KN013, median PFS was 10.4 mo (95%CI, 3.4 to not reached) with 12-mo PFS rate of 47%; median OS was 31.4 mo with 12-mo OS rate of 65% (Panel B). In KN170, median PFS was 5.5 mo (95%CI, 2.8-12.1) with 12-mo PFS rate of 38%; median OS was not reached (95% CI, 7.3 to not reached) with 12-mo OS rate of 58% (Panel B). In KN013, no new safety signals were observed compared with prior analyses. In KN170, 30 (57%) pts had a treatment-related AE (TRAE). Common (≥5%) TRAEs included neutropenia (19%), hypothyroidism and asthenia (8% each), and pyrexia (6%). 12 (23%) pts had a grade 3-4 TRAE, including 5 (9%) with grade 3 and 2 (4%) with grade 4 neutropenia. Six (11%) pts had an immune-mediated AE including 1 (2%) with grade 4 pneumonitis. There were no treatment-related deaths. Conclusion: Together with the longer follow-up results of KN013, KN170, the largest prospective clinical trial in rrPMBCL, establishes the robust antitumor activity of pembrolizumab in this disease, with exceptionally durable responses and survival in responding patients. These results provided the basis for the FDA accelerated approval of pembrolizumab in patients with rrPMBCL. Disclosures Armand: Otsuka: Research Funding; Adaptive: Research Funding; Merck: Consultancy, Research Funding; Affimed: Consultancy, Research Funding; Pfizer: Consultancy; Infinity: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Roche: Research Funding; Tensha: Research Funding. Rodig:Merck & Co., Inc.: Research Funding; Affimed Inc.: Research Funding; KITE Pharma: Research Funding; Bristol-Meyers-Squibb: Research Funding. Özcan:Jazz: Other: Travel support; Bayer: Research Funding; BMS: Honoraria; MSD: Other: travel support, Research Funding; Janssen: Other: Travel Support, Research Funding; Jazz: Other; Celgene: Other: Travel support, Research Funding; Roche: Honoraria, Research Funding; Archigen: Research Funding; Novartis: Research Funding; MSD: Research Funding; Abbvie: Other: Travel payment; Takeda: Honoraria, Other: Travel payment, Research Funding. Fogliatto:Novartis: Consultancy; Roche: Consultancy, Speakers Bureau; Janssen: Honoraria, Research Funding. Walewski:Roche, Celegene, Takeda, Janssen-Cilag, and Servier: Membership on an entity's Board of Directors or advisory committees; Roche, Celgene, Takeda, Janssen-Cilag, and Servier: Honoraria; Roche, GSK/Novartis, Takeda, and Janssen-Cilag: Research Funding. Gulbas:Pfizer: Other: Travel expenses; Roche and Janssen: Honoraria; Gilead: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees. Ribrag:Incyte Corporation: Consultancy; MSD: Honoraria; NanoString Technologies: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Other: travel; Gilead: Consultancy, Honoraria; Roche: Honoraria, Other: travel; Infinity: Consultancy, Honoraria; epizyme: Consultancy, Honoraria; Amgen: Research Funding; pharmamar: Other: travel; Servier: Consultancy, Honoraria; argenX: Research Funding. Christian:Immunomedics: Research Funding; Bristol-Myers Squibb: Research Funding; Merck: Research Funding; Acerta: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding. Perini:Janssen and Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen and Takeda: Speakers Bureau; Janssen and Takeda: Other: Travel expenses. Salles:Merck: Honoraria; Novartis: Consultancy, Honoraria; Roche: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; AbbVie: Honoraria; Acerta: Honoraria; Takeda: Honoraria; Pfizer: Honoraria; Morphosys: Honoraria; Servier: Honoraria; Amgen: Honoraria; Epizyme: Honoraria; Gilead: Honoraria; Janssen: Honoraria. Svoboda:Pharmacyclics: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Kyowa: Consultancy; Regeneron: Research Funding; TG Therapeutics: Research Funding; KITE: Consultancy; Merck: Research Funding; Seattle Genetics: Consultancy, Research Funding. Chatterjee:Merck & Co., Inc.: Employment. Orlowski:Merck & Co., Inc.: Employment. Balakumaran:Amgen: Equity Ownership; Merck & Co., Inc.: Employment, Equity Ownership. Shipp:Bayer: Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria; Merck: Research Funding. Zinzani:PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Description: Introduction: Lymphomas are an important complication of HIV infection where they occur with high frequency and are a significant cause of morbidity and mortality.The most prevalent lymphoma subtype in HIV positive population is the diffuse large B cell lymphoma (DLCBL). Antiretroviral therapy (ART) and intensive chemotherapy have been introduced to these patients aiming to increase their response to treatment. Recently, dose adjusted-EPOCH (DA-EPOCH) was associated with better outcome when compared with CHOP. Since these publications, many centers in the world started treating HIV DLBCL patients with EPOCH. In Brazil, Rituximab is not allowed for the treatment of HIV lymphomas (any subtype) in the public health system, so HIV DLBCL patients usually are treated with CHOP or DA-EPOCH. Objective:To compare the progression free survival and overall survival in HIV DLBCL patients treated with CHOP and DA-EPOCH at Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, a university public hospital from the southern part of Brazil. Material and Methods:A retrospective cohort of all HIV positive patients and DLBCL, treated from 2007 to 2017 at HCPA. The medical records were reviewed to collect clinical data, reports on pathology, immunohistochemistry, computed tomography (TC) and/or FDG-PET scan from diagnosis and after treatment. Overall survival and progression free survival was determined by the Kaplan-Meier method, and statistical significance was determined by a log-rank test. The study was approved by the institutional review board and complied with the Declaration of Helsinki. All patients gave written informed consent. Results:Forty-three HIV positive patients with untreated DLBCL were enrolled. The median age was 44 years, and 93% had a intermediate or high age-adjusted international prognostic index (aa-IPI). Specific adverse prognostic features included elevated LDH in 84%, B symptoms in 82%, Ann Arbor stage III or IV in 70% and extra-nodal disease in 81%. Central nervous system involvement was found in 9% of patients before treatment. Patients had a median CD4 cell count of 113 cells/mm3 with 21% having a CD4 cell count less than 50 cells/mm3 and 16% of patients were ART naive. Until 2014, CHOP was the chosen treatment for 34 patients. After 2014, DA-EPOCH was the prefered chemotherapy for HIV DLBCL patients and 9 patients were treated with this protocol. The progression free survival at 24 months was 69% in the CHOP group and 83% in DA-EPOCH (p=0.68). Overall survival at same period was 34.5% for CHOP vs 37% for EPOCH (p=0.74). CHOP and DA-EPOCH treatment groups presented similar features regarding the lymphoma and HIV infection, except for higher LDH level and aa-IPI score in the CHOP arm (p=0.02 and p=0.03, respectively). Discussion:The acquired immunodeficiency syndrome-related to DLBCL in this subgroup of patients was associated with a very high-risk prognostic score group. Moreover, 21% of them presented a low count of CD4 cells (less than 50 cells/mm3) at diagnosis. The overall survival was lower than expected for both groups and DA-EPOCH was not associated with better outcome when compared to CHOP. This unexpected finding could be explained in part by the small sample of patients treated with DA-EPOCH, the population prognostic features and the unavailability of rituximab in the treatment of these patients. The follow up study will provide more informations about the impact of DA-EPOCH in our HIV patients. The access to rituximab in HIV DLBCL treatment should be an important point of discussion with public health care providers in Brazil. Disclosures No relevant conflicts of interest to declare.

Description: Background:Treatment options for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) are limited. Ibrutinib is a first-in-class small-molecule inhibitor of Bruton's tyrosine kinase. These extended access programs (EAP) provided patient access to ibrutinib in Brazil and real-world safety data was collected, at a time when the medication was not commercially available in Brazil. Methods:These two prospective, multicenter, open-label EAPs of single-agent ibrutinib were conducted between April 2013 and August 2017, and enrolled Brazilian patients with relapsed/refractory CLL or MCL. Eligible patients must have progressive disease after at least one prior therapy and not suitable for retreatment with purine analogue therapy. After a 30-day screening, eligible patients received once-daily oral ibrutinib 420 mg (CLL) or 560 mg (MCL) continuously until disease progression, unacceptable toxicity, absence of clinical benefit, or end of EAP, whichever occurred first. Doses could be withheld or reduced based on toxicity. Patients were monitored for safety and disease evaluations were conducted per routine local standard of care practices. Results:Of 33 CLL patients enrolled, 32 received one dose of drug or more and were included in the safety analysis. Median age was 62.5 years, and most patients were male (n=24; 75%) and white (n=27; 84.4%). The median time from CLL diagnosis to study inclusion was 83.8 months and from diagnosis to relapsed/refractory state, 42.0 months. The median number of ibrutinib cycles was 12.0 (1.0-16.0) with a median treatment duration of 11.1 (0.9-11.6) months. Eight patients discontinued due to adverse event (AE; n = 4; 12.5%), consent withdrawal (n = 2; 6.3%), death (n = 1; 3.1%), or disease progression (n = 1; 3.1%). AEs leading to treatment discontinuation were intestinal bleeding, neutropenia, infection, and gastric tumor (one patient each). Three (9.4%) patients had dose reductions: one (3.1%) for neutropenia, febrile neutropenia with pneumonia, or worsening fatigue. 21 patients (65.6%) had at least one Grade ≥3 (G3) AE or serious AE (SAE). The most frequent G3 or SAEs included neutropenia in 8 (25.0%), fatigue (1), leukocytosis (1), and pneumonia (3). No atrial fibrillation or bleeding AEs were reported. Among the 47 G3 or SAEs, 17 (36.2%) were serious, 38 (80.9%) were suspected to be related to ibrutinib, and 39 (83.0%) were resolved without sequelae. All 13 MCL patients enrolled in the study were included in the safety analysis. The median age was 60.0 years, and most patients were male (n=9; 69.2%) and white (n=9; 69.2%). The median number of prior treatment regimens were 3. The median time from diagnosis to the first dose of ibrutinib was 20.4 months. The median number of ibrutinib cycles was 19 (4.0-34.0) with a median treatment duration of 16.8 (3.6-30.5) months. Eight patients discontinued because of either death (n=3; 23.1%) or disease progression (n=5; 38.5%). The three patients died with treatment-emergent G4 or higher AEs, including pneumonia (G5; probably treatment-related [TR]), sepsis (G5; not TR), and dyspnea (G4; doubtful TR); 8 patients (61.5%) had at least one G3 or higher treatment-emergent AE. The most frequent AE was diarrhea (n=3; 23.1%), and other AEs were reported in one patient each (i.e. abdominal hernia, anemia, appendicitis, dyspnea, febrile neutropenia, influenza, leukocytosis, neutropenia, pneumonia, productive cough, renal failure/insufficiency, retroperitoneal abscess, thrombocytopenia). Three (23.1%) patients had ibrutinib dose modifications: one (7.7%) each because of appendicitis/tuberculosis, thrombocytopenia, and diarrhea/retroperitoneal abscess/dyspnea. No atrial fibrillation or bleeding AEs were reported. Among the 20 G3 or higher treatment-emergent AEs, 14 (70%) were suspected to be related to ibrutinib and 15 (75%) were resolved. Conclusions: This is the first real-world experience with ibrutinib monotherapy for CLL and MCL in Brazil. Overall, treatment was well tolerated with no unexpected toxicities. No atrial fibrillation or bleeding AEs were reported. Of 32 patients with relapsed/refractory CLL, 24 (80%) remained on therapy, 4 (12.5%) discontinued due to AEs, 1 (3.1%) each died or experienced disease progression. Among 13 patients with relapsed/refractory MCL, 5 (38.5%) remained on the therapy, 3 (23.1%) died and 5 (38.5%) experienced disease progression. Disclosures Chiattone: Janssen: Honoraria, Research Funding. Fogliatto:Novartis: Consultancy; Janssen: Honoraria, Research Funding; Roche: Consultancy, Speakers Bureau. Scheinberg:Novartis: Consultancy, Speakers Bureau; Janssen: Honoraria, Research Funding; Pfizer: Speakers Bureau. Bigni:Janssen: Honoraria, Research Funding. Rodrigues:Janssen: Honoraria, Research Funding. Garicochea:Janssen: Honoraria, Research Funding. Pimenta:Janssen: Honoraria, Research Funding. Boechat:Janssen: Honoraria, Research Funding. Musacchio:Janssen: Honoraria, Research Funding. Goncalves:Janssen: Honoraria, Research Funding. Vieira:Janssen: Honoraria, Research Funding. Santos:Janssen: Employment. Grings:Janssen: Employment. Parisi:Janssen: Employment. Barreyro:Janssen: Employment.

Description: Glivec was the first tyrosine kinase inhibitor (TKI) approved for chronic myeloid leukemia (CML) treatment and its efficacy has been demonstrated in a large number of trials. Generic formulations have been used recently as a more cost effective treatment, but there are few studies that have prospectively evaluated the efficacy and safety of these drugs.Aims: The present study aimed to evaluate the efficacy and safety of generic imatinib in CP-CML in first line therapy. Methods: This is a multicenter, observational, cohort-type study. The prospective cohort consisted of patients who initiated treatment with generic imatinib between January 2015 and September 2017; whereas the retrospective cohort was treated with Glivec between January 2010 and December 2011. All patients started imatinib in CP, less than six months from diagnosis. Patients were managed according to European Leukemia Net (ELN) 2009 and 2013 recommendations. The definition of the responses followed the ELN 2013 criteria. Adverse events were assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.3, 2010. Event-free survival (EFS) was measured from starting date of treatment until loss of complete hematologic response, loss of major cytogenetic response, progression to accelerated (AP) or blast crisis (BC) or death from any cause at any time during initial therapy or discontinuation of imatinib by any cause. Patients that switched from Glivec to generic where censored. Overall survival (OS) was measured from starting date of imatinib until to the date of death from any cause while on therapy or last seen. Progression-free survival (PFS) was measured from starting date of imatinib to transformation to AP or BC or deaths while on therapy. Survival curves were calculated by the Kaplan-Meier method and compared with the log-rank test. Cox regression was used with Backward Wald Method. SPSS version 21.0 was used applying the chi-square and t-test, when adequate. All analysis considered p-value

Description: The treatment of chronic myeloid leukemia (CML) was revolutionized by the introduction of imatinib mesylate (IM). However, approximately 20% of patients are non-responsive and interpatient variability in response to IM is still a phenomenon lacking explanation. Single nucleotide polymorphisms (SNPs) located in genes encoding proteins involved in IM pharmacokinetics are potentially involved in the causes of this variation. In this study, we investigated the association of SNPs in the genes encoding IM metabolizing enzymes CYP3A4 (rs35599367 and rs2740574) and CYP3A5 (rs776746) and efflux transporter proteins ABCB1 (rs3213619, rs1128503, rs2032582 and rs1045642), ABCG2 (rs2231142) and ABCC4 (rs9561765) with response to treatment and with IM plasma through levels and hair concentrations. The analyzed sample was constituted of 182 CML patients on IM treatment. DNA samples were genotyped for the nine SNPs using real-time polymerase chain reaction. Hair and plasma trough IM concentrations were measured through liquid chromatography coupled to mass spectrometry methods. Clinical response was defined according to the European Leukemia Net guidelines. The number of responders to standard IM therapy was 104. A trend to a higher frequency of CYP3A4 *22 (rs35599367) allele carriers was observed among responders to IM (12.5 vs. 3.4% of non-responders, P = 0.087), although no significant differences in plasma or hair concentrations between genotypes were found. Pharmacogenetics may become a valuable approach to optimize therapy with IM in CML, but many factors still need to be clarified to make possible its application in clinical practice. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: There are few reports of standard of care and outcomes in Latin America. The HOLA study is a retrospective chart review of patients with B-cell malignancies in Latin America (LATAM). Methods: The objective of this registry is to describe patient characteristics, diagnostic and treatment patterns, and clinical outcomes in patients with Non-Hodgkin Lymphoma (NHL) from a mix of public and private sites in Brazil, Mexico, Chile, Argentina, Colombia, Guatemala, and Panama. We report 1975 patients with NHL diagnosed in the period from January 2006 to March 2016. Results: Median age according to NHL subtype was: Follicular Lymphoma (FL) 58, Mantle cell lymphoma (MCL) 61, Diffuse Large B cell Lymphoma (DBLCL) 58 and T cell lymphoma (TCL) 49 years. The cases were reviewed starting first with patients diagnosed in 2006 onwards, lost files might bias the following distribution. (Graphic1). Immunohistochemistry tests performed for each subtype are presented. For FL valuable markers to make differential diagnosis like CD5, CD23 and CD10 are not always tested. In MCL, CD5, Cyclin D1 and Ki67 were not performed for all patients. For DLBCL markers such as CD10, Bcl6 and MUM1 were performed in 36%, 25% and 17% respectively. Cytogenetic exams are not part of the regular screening of NHL in (LATAM), performed on 6% of all lymphomas. Advances stages are frequently seen for all types of lymphoma, Ann Arbor IV 27%, 54%, 27% and 29% for FL, MCL, DLBCL and TCL respectively. Most frequent extranodal involvement site for FL and MCL was bone marrow (25.4% and 41.3% respectively) and skin for DBLCL and TCL (14% and 13%). R-CHOP is the most frequently used regimen for all types of lymphoma, except for T cell lymphoma (FL 42%, MCL 45%, DLBCL 66%, TCL 7%) Hyper CVAD is more used on MCL (11%) and TCL (14%). There was a 15% use of CHOP reported for each B cell Lymphoma. Radiotherapy consolidation is most used for DLBCL and TCL (30 and 27% respectively). Transplant was more frequent for MCL, 15% vs less than 10% for the others. Higher relapse rate was seen for MCL (49%) and TCL (44%) versus 31% and 32 % for FL and DLBCL. For relapsed NHL treatment no standard of care can be highlighted (Table 2). Conclusions: The HOLA registry is a LATAM collaborative effort to show incidences of NHL subtypes, diagnosis methodologies and treatment options in the region. HOLA registry found a higher incidence of DLBCL among other LNH subtypes than reported in other regions of the world. NHL diagnosis is a regional gap, underutilization of IH markers might be related to lack of hematopathologists or low availability of specific markers. IH markers to differentiate subtypes of DLBCL are not routinely used in LATAM. Low Cytogenetic testing of NHL in LATAM. Most common first line regimen for B cell NHL was R-CHOP. There was still 15% use of CHOP without R. This might be related to low access. Second and third line treatments were heterogeneous reflecting different available options in LATAM, but no standard of care. Figure 1 Figure 1. Disclosures Pavlovsky: Novartis: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Agreda Vásquez:Roche: Consultancy. Enrico:Bristol Myers squib: Speakers Bureau; Novartis: Honoraria, Patents & Royalties. Armenta San-Sebastian:Janssen: Speakers Bureau. Ovilla:Janssen: Consultancy. Santos:Janssen: Employment. De La Mora Estrada:Janssen: Employment, Membership on an entity's Board of Directors or advisory committees.

Description: Introduction: The advent of tyrosine kinase inhibitors has changed the natural history of chronic myelogenous leukemia (CML), promoting molecular remission in a high number of patients. In 40-60% of the patients that reach deep molecular responses (RM4.5 or more) and are using imatinib mesylate for 24 months or longer, a molecular response can be maintained after the cessation of the drug. Besides improving life quality in those patients, to withdraw the medication could have a great economic impact in the health system, what is extremely important in third world countries. Objective: To estimate the economic impact of stopping imatinib mesylate in CML chronic phase patients, receiving treatment for at least 36 months and presenting deep molecular response, determinate by BCR-ABL transcripts with quantitative reverse transcriptase polymerase chain reaction (QRT-PCR), in the last 24 months. Patients and methods: A single center observational retrospective study, including all patients diagnosed with chronic phase CML, confirmed by cytogenetic or molecular exams receiving treatment at a tertiary hospital in Brazil. All patients received imatinib mesylate either in first or second line therapy. Patients presenting deep molecular response for at least 24 months, under imatinib mesylate for 36 months or more were considered eligible for discontinuation the drug. The annual coast with the treatment was estimated considering the coasts of the medication and the QRT-PCR molecular exams in the Brazilian public health system. Results: In this study, 169 patients date were analyzed, the median follow up time is 5 years (range 1-13 years), 26 (15%) of those patients are eligible for stopping imatinib mesylate according to the criteria previously mentioned. Considering the requirement of QRT-PCR exams every month in the first year of discotinuating the drug, these patients would coast proximally 1.550,00 dollars/ patients year for the public health system. This coast could be reduced to 800,00 and 520 dollars/patients year, after the second and third year of the medication withdraw, when monitoring molecular response can be done every 2 and 3 months respectively. The patients receiving imatinib mesylate, and having QTR-PCR exams every six months, in the other hand, would coast the Brazilian public health system over 31.000, 00dollars /patients year. Stopping imatinib mesylate could reduce CML chronic phase treatment coasts in up to 95%. Discussion: Discontinuating imatinib mesylate is something that must be done only in clinical trial. The economic impact projection shown in this study observed the eligibility criteria described in the literature. If stopping imatinib mesylate proves to be a safe option, studies promoting it should be done in Brazil and other third world countries, as a manner of saving resources in the health system. Furthermore, the impact in life quality free of adverse effects and the possibility of gestation in young woman is not to be ignored. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Imatinibe, a target tyrosine kinase inhibitor, have revolutionized CP-CML treatment. Considering that it is being discussed imatinibe treatment interruption in patients with MR ≥ 4.5 lasting two years or more, we believe to be important to establish predictors of major molecular response (MMR) loss. Fluctuations in BCR-ABL transcripts are being advocated to be able to predict MMR loss, although the real impact of small fluctuations among patients with in MR ≥ 4.5 is uncertain. Objective: Correlate BCR-ABL fluctuations and MMR loss in patients considered to be in MR ≥ 4.5, as well as to recognize possible factors associated with these small fluctuations. Methods: We conducted a retrospective analysis in CP-CML patients receiving imatinibe (as first or second treatment line) that achieved MR ≥ 4.5 (defined as a 4.5 log reduction on an international scale) and surveyed for BCR-ABL fluctuations. We considered a fluctuation to be a rise of at least 0.5 log of BCR-ABL transcripts. Treatment interruptions were considered only when imatinibe was not taken for 15 or more consecutive days. The presence of comorbities was evaluated by applying the Charlson Index. Results: Fifty-eight patients were evaluated between with a median follow-up 7 years. Fifty-five percent were men and 28 were women, with a median age of 46 (18 - 93) years-old, most of the patients were older than 60 yo (75,9%). Among 32 patients evaluated by the Sokal risk score 97,5% were estimated to be low or intermediate. Twenty six patients presented at least one fluctuation. Regarding the number of fluctuations per patient, 18 presented only 1 fluctuation, 5 presented 2 fluctuations and 3 patients presented 3 fluctuations. Among those patients with at least one fluctuation 3 (11%) presented MMR loss, while there was none among patients without documented fluctuations (p=0,15). Among these three patients considered to have MMR loss, two presented fluctuations that reached MR 3.0, while the other patient presented a history of long treatment suspension. More patients that interrupted treatment presented BCR-ABL fluctuations, although this difference was not statically significant (78% vs 50% p=0,11). Conclusion: Small fluctuations among patients with MR ≥ 4.5 didn't seem to correlate with MMR loss, however we do believe that our population is underpowered to rule out this difference. We considered that it very interesting that patients which reached MR 3.0 presented MMR loss (considering that the other patient had to abandon treatment during pregnancy). Disclosures No relevant conflicts of interest to declare.

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