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Patients with chronic myeloid leukemia in chronic phase (CML-CP) resistant/intolerant to ≥2 tyrosine kinase inhibitors (TKIs) are at high risk of experiencing poor outcomes because of disease biology and inadequate efficacy and/or safety of current therapies. Asciminib, a first-in-class BCR-ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to approved TKIs. In this phase 3, open-label study, patients with CML-CP previously treated with ≥2 TKIs were randomized (2:1) to receive asciminib 40 mg twice daily vs bosutinib 500 mg once daily. Randomization was stratified by major cytogenetic response (MCyR) status at baseline. The primary objective was to compare the major molecular response (MMR) rate at week 24 for asciminib vs bosutinib. A total of 233 patients were randomized to asciminib (n = 157) or bosutinib (n = 76). Median follow-up was 14.9 months. The MMR rate at week 24 was 25.5% with asciminib and 13.2% with bosutinib. The difference in MMR rate between treatment arms, after adjusting for MCyR at baseline, was 12.2% (95% confidence interval, 2.19-22.30; 2-sided P = .029). Fewer grade ≥3 adverse events (50.6% vs 60.5%) and adverse events leading to treatment discontinuation (5.8% vs 21.1%) occurred with asciminib than with bosutinib. The study showed a superior efficacy of asciminib compared with that of bosutinib, together with a favorable safety profile. These results support the use of asciminib as a new therapy in patients with CML-CP who are resistant/intolerant to ≥2 prior TKIs. This trial was registered at www.clinicaltrials.gov as #NCT03106779.

Summary Background PD-1 blockade via pembrolizumab monotherapy has shown antitumour activity and toxicity in patients with relapsed or refractory classical Hodgkin lymphoma. Here, we present interim analyses from the KEYNOTE-204 study evaluating pembrolizumab versus brentuximab vedotin for relapsed or refractory classical Hodgkin lymphoma. Methods In this randomised, open-label, phase 3 study, patients aged 18 years or older with relapsed or refractory classical Hodgkin lymphoma with measurable disease and an Eastern Cooperative Oncology Group performance status of 0 or 1 who were ineligible for or had relapsed after autologous haematopoietic stem-cell transplantation (HSCT) were enrolled at 78 hospitals and cancer centres in 20 countries and territories. Patients were randomly assigned (1:1) with an interactive voice response system to pembrolizumab 200 mg intravenously every 3 weeks or brentuximab vedotin 1·8 mg/kg intravenously every 3 weeks. Randomisation was stratified by previous autologous HSCT and status after front-line therapy. Results from the second interim analysis are presented here, with a database cutoff of Jan 16, 2020. The dual primary endpoints assessed in the intention-to-treat population were progression-free survival as assessed by blinded independent central review, and overall survival (not analysed at this interim analysis). Safety was assessed in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, NCT02684292. Recruitment for this trial is closed. Findings Between July 8, 2016, and July 13, 2018, 151 patients were randomly assigned to pembrolizumab and 153 to brentuximab vedotin. After a median time from randomisation to data cutoff of 25·7 months (IQR 23·4–33·0), median progression-free survival was 13·2 months (95% CI 10·9–19·4) for pembrolizumab versus 8·3 months (5·7–8·8) for brentuximab vedotin (hazard ratio 0·65 [95% CI 0·48–0·88]; p=0·0027). The most common grade 3–5 treatment-related adverse events were pneumonitis (six [4%] of 148 patients in the pembrolizumab group vs one [1%] of 152 patients in the brentuximab vedotin group), neutropenia (three [2%] vs 11 [7%]), decreased neutrophil count (one [1%] vs seven [5%]), and peripheral neuropathy (one [1%] vs five [3%]). Serious treatment-related adverse events occurred in 24 (16%) of 148 patients receiving pembrolizumab and 16 (11%) of 152 patients receiving brentuximab vedotin. One treatment-related death due to pneumonia occurred in the pembrolizumab group. Interpretation Pembrolizumab showed statistically significant and clinically meaningful improvement in progression-free survival compared with brentuximab vedotin, with safety consistent with previous reports. These data support pembrolizumab as the preferred treatment option for patients with relapsed or refractory classical Hodgkin lymphoma who have relapsed post-autologous HSCT or are ineligible for autologous HSCT. Funding Merck Sharp & Dohme Corp (a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA). Translation For the Portuguese translation of the Article see Supplementary Materials section.

This manuscript summarizes the results of the consensus meeting composed of hematologists and cardiologists to establish recommendations for the prevention and follow-up of cardiovascular (CV) risk in patients with chronic myeloid leukemia (CML) treated with BCR-ABL tyrosine kinase inhibitors (TKIs) from the point of view of clinical practice and from the perspective of hematology consultation.In the first medical appointment, the CV risk factors should be identified to perform the baseline risk stratification, based on the Brazilian Guideline of Dyslipidemia and Atherosclerosis Prevention Update (risk levels: very high, high, intermediate and low).Once stratified, the treatment of the CV risk factors should be administered. If the patient presents risk factors, such as hypertension, diabetes, renal disease, smoking and hypercholesterolemia, the evaluation and initial treatment may be done by the hematologist, being an option the request for evaluation by a specialist. If the patient has a history of previous CV disease, we recommend referral to a specialist. As the CV risk score is dynamic and the control of risk factors can reduce the patient risk, this expert consensus recommends that the re-evaluation of the CV risk after the baseline should be performed at 3 months, 6 months and 12 months. After this period, it should be done annually and, for specific patients, at the clinician's discretion.The evaluation of the baseline CV risk and the safe administration of a TKI allow the patient to benefit from the maximum treatment, avoiding unwanted effects.

PURPOSE Patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) have a poor prognosis, and their treatment represents an urgent and unmet need. Because PMBCL is associated with genetic aberrations at 9p24 and overexpression of programmed cell death-1 (PD-1) ligands (PD-L1), it is hypothesized to be susceptible to PD-1 blockade. METHODS In the phase IB KEYNOTE-013 (ClinicalTrials.gov identifier: NCT01953692 ) and phase II KEYNOTE-170 (ClinicalTrials.gov identifier: NCT02576990 ) studies, adults with rrPMBCL received pembrolizumab for up to 2 years or until disease progression or unacceptable toxicity. The primary end points were safety and objective response rate in KEYNOTE-013 and objective response rate in KEYNOTE-170. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Exploratory end points included association between biomarkers and pembrolizumab activity. RESULTS The objective response rate was 48% (7 complete responses; 33%) among 21 patients in KEYNOTE-013 and 45% (7 complete responses; 13%) among 53 patients in KEYNOTE-170. After a median follow-up time of 29.1 months in KEYNOTE-013 and 12.5 months in KEYNOTE-170, the median duration of response was not reached in either study. No patient with complete response experienced progression, including 2 patients with complete response for at least 1 year off therapy. Treatment-related adverse events occurred in 24% of patients in KEYNOTE-013 and 23% of patients in KEYNOTE-170. There were no treatment-related deaths. Among 42 evaluable patients, the magnitude of the 9p24 gene abnormality was associated with PD-L1 expression, which was itself significantly associated with progression-free survival. CONCLUSION Pembrolizumab is associated with high response rate, durable activity, and a manageable safety profile in patients with rrPMBCL.

Background: Diffuse large B-cell lymphoma, among non-Hodgkin lymphomas, is one of the most frequent subtypes. Clinical laboratory data and post-treatment outcomes are scarce in the Brazilian population. Objective: The main objective of this retrospective study was to assess the impact of tumor markers, including the Myeloid differentiation primary response 88 (MYD88) mutation. Method: Eighty-three patients were included and treated with R-CHOP or R-CHOP-like regimens. Results: Median age was 64-years old and 58% were female patients. The median follow-up was 42 months. The progression free survival (PFS) at this time was 63% and overall survival (OS), 66%. In the patients with tumors expressing Myc proto-oncogene protein (MYC) and B-cell lymphoma 2 (BCL2), assessed by immunohistochemistry (IHC), known as dual protein expressers, median post-progression survival was 31 (15–45) months. An increased proliferative index were associated with a high rate of progression (hazard ratio 2.31 [95% confidence interval [1.05–5.12]; p = 0.04). The cell of origin (COO), identified by IHC, was not able to predict PFS (p = 0.76). The MYD88 L265P mutation was present in 10.8% (9/83) of patients and did not show a prognostic correlation. Conclusion: In conclusion, the MYD88 mutation, although an important tool for diagnosis and a possible target drug, presented at a low frequency and was not a prognostic marker in this population. Keywords: Diffuse large B-cell lymphomas, MYD88, DLBCL, Tumor markers

Aim: This study aimed to evaluate efficacy and safety of generic imatinib (IM) compared to branded imatinib (Glivec) in chronic myeloid leukemia. The primary end-point was the achievement of a major molecular response (MMR) at 12 months and safety. Secondary end-points included response evaluation, overall (OS), event-free survival (EFS) progression-free survival (PFS) and toxicity. Methods: Ambispective, multicenter, observational, non-inferiority study, in newly diagnosed Brazilian patients with chronic phase CML patients treated with IM in first line. The historic cohort consisted of CML patients treated with branded IM (Glivec) from January 2010 to December 2011 and the prospective cohort was treated with generics between January 2015 and December 2018. A total of 493 cases (214 Glivec and 279 Generic) from 10 centers were enrolled, and 393 (80%) patients were eligible for analysis (Glivec = 163; Generics = 230). EFS was measured from the start of treatment until loss of complete hematologic response, loss of major cytogenetic response, progression to accelerated or blast crisis, no response or insufficient response to study therapy, after a predefined period of time or death from any cause at any time during initial therapy or permanent discontinuation of IM by adverse events. Results: The median age was 45 and 49 years in Glivec and Generics groups, respectively (p = 0.056). Sokal score stratification in Glivec and generic groups, was respectively: low risk 50/50%; intermediate risk 49/38% and high risk 12/22% (p = 0.05). E14a2 (b3a2) frequency was 63% vs. 52% in Glivec and Generic group, respectively, and e13a2 (b2a2) 36% in both groups, e14a2+e13a2 were 1% vs. 12% (p = 0.005). There was no significant difference in gender, Eutos score and ECOG. The median time between diagnosis and treatment starting was 40 (0-169) and 28 (0-168) days (Glivec vs. Generics, respectively), p = 0.17. MMR rate at 12 months was 77/142 (54%) and 88/145 (61%) in Glivec and generics groups, respectively (p = 0.26). There were more failures in the generics group at 6 months (21% vs. 14%) (p = 0.03, respectively). There was no difference in grade 3-4 hematological and non-hematological toxicity in in the first 12 months. EFS at 24 months were higher in Glivec cohort and 76% vs. 53%, p < 0.0001, respectively), PFS and OS was not significantly different (respectively: 96% vs. 93%, p = 0.09 and 97% vs 96%, p = 0.41). The independent risk factors associated with inferior EFS were: generics use (HR = 1.78; 95%CI 1.06-2.99; p = 0.02) and High Sokal index (HR 2.25; 95%CI 1.38-3.67; p = 0.001). Conclusion: In the intention to treat analysis there was no significant difference in the primary end-point (MMR and safety at 12 months). The generics cohort presented more failures at 6 months compared to branded imatinib and inferior 24 month-EFS. There was no difference in the 24-month OS and PFS. The interpretation of the results should take into consideration the differences in CML management over the years.

Context: Results from ELEVATE-TN (NCT02475681) at a median follow-up of 28.3 months demonstrated superior efficacy of acalabrutinib (A) ± obinutuzumab (O) compared with O + chlorambucil (Clb) in TN CLL (Sharman et al. Lancet 2020;395:1278-91). Objective: To report the results from a 4-year update of ELEVATE-TN. Design: Randomized, multicenter, open-label, 3-arm, Phase 3 study. Patients: TN CLL. Interventions: Patients received A±O or O+Clb. Crossover to A monotherapy was permitted in patients who progressed on O+Clb. Main Outcome Measures: Investigator-assessed (INV) progression-free survival PFS, INV ORR, OS, and safety were evaluated. Results: 535 patients (A+O, n=179; A, n=179; O+Clb, n=177) were randomized with a median age of 70 y; 14% had del(17p) and/or mutated TP53. At a median follow-up of 46.9 months (range, 0.0–59.4; data cutoff: Sept 11, 2020), median PFS was not reached (NR) for A+O and A patients vs 27.8 months for O+Clb patients (both P Conclusions: With a median follow-up of 46.9 months (~4y), the efficacy and safety of A+O and A monotherapy was maintained, with an increase in CR since the interim analysis (from 21% to 27% [A+O] and from 7% to 11% [A]) and low rates of discontinuation.

Background: Acalabrutinib is a selective, covalent Bruton tyrosine-kinase inhibitor with activity in chronic lymphocytic leukaemia. We compare the efficacy of acalabrutinib with or without obinutuzumab against chlorambucil with obinutuzumab in patients with treatment-naive chronic lymphocytic leukaemia. Methods: ELEVATE TN is a global, phase 3, multicentre, open-label study in patients with treatment-naive chronic lymphocytic leukaemia done at 142 academic and community hospitals in 18 countries. Eligible patients had untreated chronic lymphocytic leukaemia and were aged 65 years or older, or older than 18 years and younger than 65 years with creatinine clearance of 30–69 mL/min (calculated by use of the Cockcroft-Gault equation) or Cumulative Illness Rating Scale for Geriatrics score greater than 6. Additional criteria included an Eastern Cooperative Oncology Group performance status score of 2 or less and adequate haematologic, hepatic, and renal function. Patients with significant cardiovascular disease were excluded, and concomitant treatment with warfarin or equivalent vitamin K antagonists was prohibited. Patients were randomly assigned (1:1:1) centrally via an interactive voice or web response system to receive acalabrutinib and obinutuzumab, acalabrutinib monotherapy, or obinutuzumab and oral chlorambucil. Treatments were administered in 28-day cycles. To reduce infusion-related reactions, acalabrutinib was administered for one cycle before obinutuzumab administration. Oral acalabrutinib was administered (100 mg) twice a day until progressive disease or unacceptable toxic effects occurred. In the acalabrutinib-obinutuzumab group, intravenous obinutuzumab was given on days 1 (100 mg), 2 (900 mg), 8 (1000 mg), and 15 (1000 mg) of cycle 2 and on day 1 (1000 mg) of cycles 3–7. In the obinutuzumab-chlorambucil group, intravenous obinutuzumab was given on days 1 (100 mg), 2 (900 mg), 8 (1000 mg), and 15 (1000 mg) of cycle 1 and on day 1 (1000 mg) of cycles 2–6. Oral chlorambucil was given (0·5 mg/kg) on days 1 and 15 of each cycle, for six cycles. The primary endpoint was progression-free survival between the two combination-therapy groups, assessed by independent review committee. Crossover to acalabrutinib was allowed in patients who progressed on obinutuzumab-chlorambucil. Safety was assessed in all patients who received at least one dose of treatment. Enrolment for this trial is complete, and the study is registered at ClinicalTrials.gov, NCT02475681. Findings: Between Sept 14, 2015, and Feb 8, 2017, we recruited 675 patients for assessment. 140 patients did not meet eligibility criteria, and 535 patients were randomly assigned to treatment. 179 patients were assigned to receive acalabrutinib-obinutuzumab, 179 patients were assigned to receive acalabrutinib monotherapy, and 177 patients were assigned to receive obinutuzumab-chlorambucil. At median follow-up of 28·3 months (IQR 25·6–33·1), median progression-free survival was longer with acalabrutinib-obinutuzumab and acalabrutinib monotherapy, compared with obinutuzumab-chlorambucil (median not reached with acalabrutinib and obinutuzumab vs 22·6 months with obinutuzumab, hazard ratio [HR] 0·1; 95% CI 0·06–0·17, p

INTRODUCTION: Asciminib is the first BCR-ABL1 inhibitor that potently inhibits kinase activity of the BCR-ABL1 oncoprotein by Specifically Targeting the ABL Myristoyl Pocket (STAMP). The primary analysis from ASCEMBL, a randomized, phase 3 trial, demonstrated that asciminib has superior efficacy and a better safety and tolerability profile than bosutinib (BOS) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior ATP-binding tyrosine kinase inhibitors (TKIs). The major molecular response (MMR) rate at wk 24 was 25.5% with asciminib vs 13.2% with BOS; the difference in MMR rates, after adjusting for major cytogenetic response status at baseline, was 12.2% (95% CI, 2.19-22.30; 2-sided P=.029). Grade ≥3 adverse events (AEs) were reported in 50.6% and 60.5% of pts receiving asciminib and BOS, respectively, and AEs leading to discontinuation in 5.8% and 21.1%, respectively. After a median follow-up of 19.2 months (or 7.5 months' additional follow-up since the primary analysis), we report updated efficacy and safety results from ASCEMBL. METHODS: Adults with CML-CP treated with ≥2 prior TKIs were randomized 2:1 to asciminib 40 mg twice daily (BID) or BOS 500 mg once daily (QD). Eligible pts must have experienced treatment failure (lack of efficacy) per 2013 European LeukemiaNet recommendations for second-line TKI therapy or intolerance of the most recent TKI at screening. Pts intolerant of their most recent TKI were eligible only if they had BCR-ABL1 on the International Scale >0.1% at screening. Pts with known BOS-resistant T315I or V299L mutations were ineligible. The cutoff date for the current analysis was January 6, 2021. RESULTS: A total of 233 pts were randomized to receive either asciminib (n=157) or BOS (n=76). At cutoff, all randomized pts had completed their wk 48 visit or had discontinued earlier. Treatment was ongoing in 89 (56.7%) and 17 (22.4%) pts on asciminib and BOS, respectively; the most common reason for treatment discontinuation was lack of efficacy in 37 (23.6%) and 27 (35.5%) pts, respectively (Table 1). By wk 48, the cumulative incidence of MMR was 33.2% with asciminib and 18.6% with BOS, showing that the difference between the 2 treatment arms observed by wk 24 in the primary analysis was maintained with longer follow-up (Figure 1). The cumulative incidence of BCR-ABL1IS ≤1% by wk 48 in patients without this level of response at baseline was 50.8% with asciminib and 33.7% with BOS. The difference in deep molecular responses (MRs) favoring asciminib vs BOS persisted by wk 48: MR 4 (BCR-ABL1IS ≤0.01%) and MR 4.5 (BCR-ABL1IS ≤0.0032%) rates were 14.0% and 9.6% with asciminib and 6.6% and 2.6% with BOS, respectively. With a longer duration of exposure in the asciminib arm, the safety and tolerability profile in the current analysis remains similar to that at the primary analysis. Median duration of exposure was 67.1 wk (range, 0.1-162.1 wk) for asciminib and 29.7 wk (range, 1.0-149.3 wk) for BOS. By the cutoff date, 91.0% of pts on asciminib and 97.4% of pts on BOS reported ≥1 all-grade AE; 54.5% and 67.1% of pts, respectively, reported ≥1 grade ≥3 AE. No additional fatal events were reported since the primary analysis. Fewer pts in the asciminib (7.1%) than BOS (25.0%) arm experienced AEs leading to treatment discontinuation (Table 2). The most common AEs leading to treatment discontinuation included thrombocytopenia (3.2%) and neutropenia (2.6%) in the asciminib arm and increased alanine aminotransferase (5.3%) and neutropenia (3.9%) in the BOS arm. CONCLUSIONS: Resistant/intolerant CML-CP after 2 lines of TKI treatment remains BCR-ABL1 dependent. The novel STAMP inhibitor asciminib demonstrates continued superior efficacy and a limited adverse event profile; myelosuppression, while more prominent, appears to be early and disease related. Secondary resistance based on loss of MMR is rare. Overall, after a median follow-up of 19.2 months, the positive benefit-risk profile of asciminib vs BOS continues to support the use of asciminib as a new therapy in this heavily pretreated pt population. This study is sponsored by Novartis. Figure 1 Figure 1. Disclosures Mauro: Sun Pharma / SPARC: Research Funding; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Takeda: Consultancy. Minami: Takeda: Honoraria; CMIC: Research Funding; Astellas: Honoraria; Ono: Research Funding; Pfizer Japan Inc.: Honoraria; Novartis Pharma KK: Honoraria; Bristol-Myers Squibb Company: Honoraria. Rea: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hochhaus: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Incyte: Research Funding. Lomaia: Novartis: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Pharmstandard: Honoraria. Voloshin: Abbvie: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Astra Zeneca: Consultancy, Speakers Bureau; Pfizer: Consultancy; Biacad: Consultancy, Speakers Bureau. Turkina: Pharmstandart: Speakers Bureau; Novartis Pharma: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Pfizer: Speakers Bureau. Kim: Novartis: Research Funding; BMS: Research Funding; Pfizer: Research Funding; ILYANG: Research Funding; Takeda: Research Funding. Apperley: Bristol Myers Squibb, Novartis: Honoraria, Speakers Bureau; Incyte, Pfizer: Honoraria, Research Funding, Speakers Bureau. Cortes: Sun Pharma: Consultancy, Research Funding; Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Astellas, Novartis, Pfizer, Takeda, BioPath Holdings, Incyte: Consultancy, Research Funding; Bio-Path Holdings, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Fogliatto: AstraZeneca: Speakers Bureau. Kim: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Research Funding; Paladin: Honoraria, Research Funding; Bristol-Meier Squibb: Research Funding. le Coutre: Pfizer: Honoraria; Novartis: Honoraria; Incyte: Honoraria; Bristol Myers Squibb: Honoraria. Saussele: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Pfizer: Honoraria; Roche: Honoraria. Hughes: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Incyte: Honoraria. Chaudhri: Abbvie: Honoraria; Novartis: Honoraria; Astra Zeneca: Honoraria. Chee: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Garcia Gutierrez: Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Sasaki: Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding. Kapoor: Novartis: Current Employment, Current equity holder in publicly-traded company. Allepuz: Novartis: Current Employment, Current equity holder in publicly-traded company. Quenet: Novartis: Current Employment. Bédoucha: Novartis: Current Employment. Boquimpani: Pinth Pharma: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jansen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Coronavirus disease (COVID-19) is an infectious disease caused by the newly discovered coronavirus Sars-Cov2. In Brazil, the first COVID-19 case was diagnosed in February 2020, and since then, the number of cases and deaths has increased exponentially, reaching 2.610.102 confirmed cases and 91.263 deaths on July 31st. Most people have a mild to moderate respiratory illness, but the clinical evolution may be severe in older adults and patients with comorbidities, such as cancer. There are few reports of COVID-19 in patients with chronic myeloid leukemia (CML). This ongoing study aims to collect data about COVID-19 in CML patients from Brazil and their outcomes. Methods: This is an observational, multicentric, ongoing register study. Hematologists from private and public CML reference centers from different regions of Brazil were invited to report their cases of COVID-19 in CML patients. Altogether, those centers are responsible for the care of approximately 4336 CML patients. COVID-19 was classified as mild/moderate, severe (defined as tachypnoea [≥30 breaths per min], oxygen saturation ≤93% at rest, or PaO2/FiO2 ratio Results: Between March and July 2020, 24 institutions contributed to this analysis, and reported 28 COVID-19 cases in CML patients. Eighteen centers were from the South and Southeast regions, 5 from Northeast, and one from the Central region. There were 19 cases (67.9%) from the Southeast region, 8 (28.6%) from the Northeast, one from South (3.6%). The median age was 54 years (24-79), with 13 (44%) older than 60. Male patients were predominant (67.9%). There was one patient in the accelerated phase. There were two cases of COVID-19 simultaneous to CML diagnosis, 10 using imatinib, 7 dasatinib, 6 nilotinib, one ponatinib, one asciminib, and one patient in treatment-free remission after imatinib discontinuation. The median time of CML diagnosis was 7.0 years (0-26). Current CML response was: no hematologic response (n=8), hematologic response (n=4), major molecular response (n=9), MR4.0 or MR5.0 (n= 7). Eleven patients interrupted treatment temporarily during COVID. COVID-19 was confirmed by RT-PCR of oral and nasal swab collection (20) or serologic test (07). One case is suspect, awaiting confirmation. The majority of the patients presented at least one comorbidity (60%): hypertension (7), diabetes (3), chronic renal failure (1), dyslipidemia (2), arterial disease (2), cirrhosis (1), chronic obstructive pulmonary disease/emphysema (2), pulmonary hypertension (1), HTLV1 (1), obesity (n=1). COVID-19 severity: mild/moderate (19), severe/critic (9). Five out of 9 (55%) of the severe/critic cases were older than 60, 4/9 presented comorbidities and 5/9 (55%) had no major molecular response (MMR)(one was in accelerated phase, one newly diagnosed, and 3 with only hematologic response). Among the mild/moderate cases, 12/19 had optimal response (63%) and 7/19 (36%) had no hematologic response. Twenty-one patients recovered, 4 are still hospitalized, and 3 died from COVID: one newly diagnosed case with high leukocytes counts and with a simultaneous bacterial infection, one elderly patient with comorbidities treated with imatinib and one patient treated with nilotinib, with hematologic response. A fourth patient in the accelerated phase died 2 months after discharge, from disease progression and pulmonary infection. Conclusion: Although the sample size is still small to make conclusions regarding COVID-19 behavior in CML patients, the most severe cases occurred in patients not in MMR. The continued register of the cases will increase our knowledge about this disease and how to manage these patients. Disclosures Pagnano: Astellas: Other: Advisory Board and lecture; Novartis: Other: Advisory Board; EMS: Other: Lecture; Pintpharma: Other: Lecture. Magalhães:AstraZeneca: Speakers Bureau; Novartis: Speakers Bureau. Santos:Novartis: Other: Speaker fee; Bristol-Myers Squibb: Other: Speaker fee. Clementino:EMS: Other: Financial support for congress.

7509 Background: Early results from ELEVATE-TN (NCT02475681) at a median follow-up of 28.3 mo demonstrated superior efficacy of acalabrutinib (A) ± obinutuzumab (O) compared with O + chlorambucil (Clb) in patients (pts) with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) (Sharman et al. Lancet 2020;395:1278-91). Results from a 4-year update are reported here. Methods: Pts received A±O or O+Clb. Crossover to A monotherapy was permitted in pts who progressed on O+Clb. Investigator-assessed (INV) progression-free survival (PFS), INV overall response rate (ORR), overall survival (OS), and safety were evaluated. Results: 535 pts (A+O, n=179; A, n=179; O+Clb, n=177) were randomized with a median age of 70 y; 63% had unmutated IGHV and 9% del(17p). At a median follow-up of 46.9 mo (range, 0.0–59.4; data cutoff: Sept 11, 2020), the median PFS was not reached (NR) for A+O and A pts vs 27.8 mo for O+Clb pts (both P

7545 Background: Obinutuzumab (G)-chemotherapy (chemo) has demonstrated improved progression-free survival compared with rituximab (R)-chemo in previously untreated advanced follicular lymphoma (FL). G is currently administered by IV infusion over ̃3–4 hours. A shorter duration of infusion in Cycle (C) 2 and subsequent cycles, as is standard practice with R, could improve convenience for patients (pts) and efficiency for infusion facilities. We report the primary analysis of the prospective, open-label, multicenter, single-arm, Phase IV, GAZELLE study (NCT03817853), which evaluated the safety of G administered as a 90-minute (min) SDI from C2 onwards in pts with FL. Methods: Pts with previously untreated FL received G (1000mg) intravenously on Day (D) 1, 8, and 15 of C1, and on D1 thereafter, plus chemo (bendamustine, CHOP, or CVP) for 6–8 cycles. In C1, pts received G at the standard infusion rate. Pts without a Grade (Gr) ≥3 infusion-related reaction (IRR) in C1 were eligible to receive G as a 90-min SDI from C2. Pts with a Gr 3 IRR in C1 received the standard G infusion in C2, and were eligible for G SDI in subsequent cycles if no Gr ≥3 IRRs occurred. Pts with a second Gr 3/4 IRR discontinued G. At the end of induction (EOI), responding pts received maintenance G (1000mg) as SDI for 2 years or until disease progression (PD). The primary endpoint was incidence of Gr ≥3 IRRs during C2. IRRs were defined as any event occurring ≤24 hours from infusion judged to be related to treatment. Secondary endpoints included adverse events (AEs) and investigator-assessed overall response rate at EOI. Results: As of December 3, 2020, 113 pts had received study treatment. Median age was 62.0 years, 50.4% were male, 61.9% had stage IV FL, and 45.1% were classified as high-risk FLIPI. Of the 110 pts who were eligible for G SDI from C2, no pt experienced a Gr ≥3 IRR with SDI in C2 (Table). One pt experienced a Gr 3 IRR with SDI in C5, presenting hypertension. All other IRRs with SDI were Gr 1/2. No Gr 4/5 IRRs were reported. Other AEs were similar to those observed in previous studies. At the clinical cut-off date, 104 pts had a CT imaging-based response assessment at EOI and 9 pts had no response assessment; 76/113 (67.3%) had a complete response, 22 (19.5%) had a partial response, and six (5.8%) had PD. Conclusions: In GAZELLE, G SDI in C2 and beyond appeared to be safe. No Gr 3 IRRs were observed in C2 and only one Gr 3 IRR was reported in subsequent cycles. The safety profile of G SDI was comparable with the established profile of G in advanced FL. Clinical trial information: NCT03817853. [Table: see text]

Introduction: The open-label, international, randomized, phase 3 KEYNOTE-204 (NCT02684292) study showed that in pts with R/R cHL, the PD-1 inhibitor pembro was superior to BV and demonstrated statistically significant, clinically meaningful improvement in PFS, with safety consistent with previous reports. This post hoc exploratory analysis of KEYNOTE-204 evaluated pembro vs BV by number of prior lines of therapy. Methods: Eligible pts were aged ≥18 y, had measurable disease and ECOG PS 0 or 1, and were post−autologous stem cell transplant (auto-SCT) or ineligible for auto-SCT. Pts who were BV-naive or BV-exposed were also eligible. Pts were randomized 1:1 to pembro 200 mg IV Q3W or BV 1.8 mg/kg IV Q3W. Randomization was stratified by status after 1L therapy (primary refractory vs relapsed Results: Of 304 randomized pts, 55 (pembro, 27; BV, 28) received 1 prior therapy and 249 (pembro, 124; BV, 125) received ≥2 prior therapies. For pts with 1 prior therapy, median (range) age was 49 y (22-84) and 22 pts (40.0%) were aged ≥65 y. No pts received prior auto-SCT and 18 (32.7%) had primary refractory disease. Auto-SCT ineligibility was due to chemorefractory disease for 21 pts (38.2%) and reasons not related to chemorefractory disease (eg, age, comorbidities) for 34 pts (61.8%). 23 pts (85.2%) and 25 pts (92.6%) in the pembro and BV groups, respectively, discontinued treatment; the most common reason was progressive disease. Median (range) time from randomization to data cutoff was 24.0 mo (18.7-34.8) for pembro and 23.6 mo (18.2-34.6) for BV. For the primary PFS analysis, median PFS was 16.4 mo for pembro and 8.4 mo for BV (HR 0.70; 95% CI 0.031-1.59); 12 mo PFS rates were 58.9% and 37.4%, respectively. For the secondary PFS analysis, median PFS was 11.7 mo for pembro and 8.3 mo for BV (HR 0.62; 95% CI 0.28-1.40). ORR was 66.7% for pembro and 53.6% for BV. Median (range) DOR for pembro was 20.7 mo (2.8-20.7) and 14.1 mo (0.0+ to 21.9) for BV. 7 pts (25.9%) and 9 pts (33.3%) in the pembro and BV groups, respectively, received subsequent auto-SCT; 1 pt in the BV group received subsequent allo-SCT. 21 pts (77.8%) on pembro and 20 (74.1%) on BV experienced a treatment-related adverse event (TRAE); most common were hyperthyroidism (22.2%) for pembro and peripheral neuropathy (22.2%) for BV. 1 (3.7%) and 8 (29.6%) of pts on pembro and BV, respectively, experienced grade 3-5 TRAEs. For pts with ≥2 prior therapies median (range) age was 34 y (18-83) and 27 (10.8%) pts were aged ≥65 y. 112 pts (45.0%) received prior auto-SCT and 105 (42.2%) had primary refractory disease. Median (range) time from randomization to data cutoff was 27.1 mo (18.8-42.0) for pembro and 27.6 (18.2-42.3) for BV. 87 (71.9%) and 121 (96.8%) in the pembro and BV groups discontinued; most common reason was progressive disease. For the primary PFS analysis, median PFS was 12.6 mo for pembro and 8.2 mo for BV (HR 0.66; 95% CI 0.47-0.92); 12-mo PFS rates were 52.8% and 35.3%, respectively. For the secondary PFS analysis, median PFS was 12.6 mo for pembro and 8.2 mo for BV (HR 0.63; 95% CI 0.45-0.88). ORR for pembro was 65.3% and 54.4% for BV. Median (range) DOR for pembro was 20.5 mo (0.0+ to 33.2+) and 11.2 mo (0.0+ to 33.9+) for BV. 23 (19.0%) and 25 (20.0%) pts in the pembro and BV groups, respectively, received subsequent auto-SCT; 14 (11.6 %) and 12 (9.6%) received subsequent allo-SCT. 89 pts (73.6%) on pembro and 97 (77.6%) on BV experienced a TRAE; most common were hypothyroidism (14.9%) for pembro and peripheral neuropathy (17.6%) for BV. 23.1% and 24.0% of pts on pembro and BV, respectively, experienced grade 3-5 TRAEs. Conclusion: In pts with R/R cHL, pembro monotherapy resulted in an improvement in PFS and ORR vs BV in pts regardless of number of prior therapies. In particular, these data suggest that pembro monotherapy may be a promising option as 2L+ therapy for pts with R/R cHL ineligible for auto-SCT. Disclosures Kuruvilla: Bristol-Myers Squibb Company: Consultancy; TG Therapeutics: Honoraria; Pfizer: Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy; Karyopharm: Consultancy, Honoraria; AstraZeneca Pharmaceuticals LP: Honoraria, Research Funding; Novartis: Honoraria; Antengene: Honoraria; Merck: Consultancy, Honoraria; Celgene Corporation: Honoraria; Amgen: Honoraria; Roche: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria. Ramchandren:Seattle Genetics, Sandoz-Novartis, Pharmacyclics, an AbbVie Company, Janssen, Bristol-Myers Squibb: Consultancy; Merck, Seattle Genetics, Janssen, Genentech: Research Funding. Santoro:Arqule, Sanofi: Consultancy; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy, Speakers Bureau; Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, MSD: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau. Paszkiewicz-Kozik:Roche, Takeda, Celgene: Other: Travel, accommodations, expenses. Gasiorowski:MSD, Takeda, Novartis, AbbVie: Honoraria. Johnson:Roche/Genentech, Merck: Honoraria; Roche/Genentech, Merck, Bristol-Myers Squibb, AbbVie: Consultancy; AbbVie: Research Funding. Goncalves:Janssen, Takeda, Amgen, Bayer, Novartis, Merck, Bayer, Celgene, GSK, BMS: Research Funding; Janssen: Consultancy, Speakers Bureau. Perini:Janssen, Takeda: Honoraria; AbbVie, Janssen: Speakers Bureau. Goldschmidt:Abbvie Inc: Consultancy, Research Funding. Kryachok:Janssen, Bayer, Karyopharm, MSD, AbbVie, Acerta, Debiopharm: Research Funding; Takeda, Janssen: Consultancy; Takeda, MSD, AbbVie, Roche: Other: Travel, accommodations, expenses. Sekiguchi:Ono, A2 Healthcare, Astellas, Janssen, Merck Sharp & Dohme, Otsuka, Pfizer, PPD-SNBL, Sumitomo Dainippon, Daiichi Sankyo, and Bristol-Myers Squibb: Research Funding. Lin:Merck & Co., Inc.: Current Employment. Nahar:Merck Sharp & Dohme, Corp., a subsididary of Merck & Co., Inc., Kenlworth, NJ, USA: Current Employment. Marinello:Merck & Co., Inc.: Other: Travel, accommodations, expenses; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA: Current Employment; Merck & Co., Inc., Kenilworth, NJ, USA: Other: Stock ownership. Zinzani:Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

8005 Background: PD-1 blockade via pembro monotherapy showed antitumor activity in R/R cHL. KEYNOTE-204 (NCT02684292) was a randomized, international, open-label, phase III study of pembro vs BV in R/R cHL. Methods: Patients (pts) were aged ≥18 y, were post−autologous stem cell transplant (auto-SCT) or ineligible for auto-SCT, and had measurable disease and ECOG PS 0 or 1. BV-naive and BV-exposed pts were eligible. Pts were randomized 1:1 to pembro 200 mg IV Q3W or BV 1.8 mg/kg IV Q3W and stratified by prior auto-SCT (yes vs no) and status after 1L therapy (primary refractory vs relapsed

Introdução: O filgrastim, que desempenha um papel fundamental na coleta de células progenitoras de sangue periférico (CPSP), está disponível há quase 25 anos, e existem vários biossimilares de filgrastim sendo comercializados. Objetivo: Avaliar se um filgrastim biossimilar (Filgrastine®) foi associado com mobilização efetiva em pacientes submetidos à coleta de CPSP para transplante autólogo de medula óssea. Método: Foram revisados os prontuários de pacientes com mieloma múltiplo e linfomas tratados em três instituições no Brasil. O desfecho primário (taxa de sucesso de mobilização) foi a proporção de pacientes na população intenção de tratar (ITT), em que pelo menos 2 x 106 células CD34+/kg foram coletadas por leucaférese nos dias 5 e/ou 6. A população per protocolo (PP) foi composta por pacientes que receberam pelo menos quatro dias de Filgrastine e tiveram pelo menos uma contagem de CD34+ nos dias 5 ou 6. Resultados: A dose diária de Filgrastine (no D1, com pequenas alterações subsequentes) variou de 8,5 a 28,9 mcg/Kg nos 52pacientes na população ITT, com uma mediana de 13,8 mcg/Kg; 51 pacientes receberam pelo menos quatro doses. Uma média de 2,84±1,97 x 106 células CD34+/kg foram coletadas. A taxa de sucesso de mobilização foi de 53,9% (IC 95%, 39,5% a 67,8%) na população ITT e 62,2% (IC 95%, 46,5% a 76,2%) nos 45 pacientes da população PP. A mobilização foi considerada efetiva pelos pesquisadores em 80,8% dos pacientes da população ITT e 88,9% daqueles na população PP. Conclusão: Apesar de sua natureza observacional, este estudo sugere que Filgrastine esteja associado com as taxas de sucesso esperadas na coleta de CPSP para transplante autólogo de medula óssea. Introducción: El filgrastim, que desempeña un papel fundamental en la colecta de células progenitoras de sangre periférica (CPSP), está disponible desde hace casi 25 años y existen varios biosimilares de filgrastim siendo comercializados. Objetivo: Se evaluó si un filgrastim biosimilar (Filgrastine®) se asoció con una movilización efectiva en pacientes sometidos a la colecta de CPSP para el trasplante autólogo de médula ósea. Método: Se revisaron los prontuarios de pacientes con mieloma múltiple y linfomas tratados en tres instituciones en Brasil. El resultado primario (tasa de éxito de movilización) fue la proporción de pacientes en la población intención de tratar (ITT) en que al menos 2 x 106 células CD34+/kg fueron obtenidas por leucoféresis en los días 5 y/o 6. La población por protocolo (PP) fue compuesta por pacientes que recibieron por lo menos 4 días de Filgrastine y tuvieron al menos un recuento de CD34 + en los días 5 o 6. Resultados: La dosis diaria de Filgrastine (en el D1, con pequeños cambios subsiguientes) varió de 8, 5 a 28,9 mcg/Kg en los 52 pacientes en la población ITT, con una mediana de 13,8 mcg / Kg; 51 pacientes recibieron al menos cuatro dosis. Se obtuvo una media de 2,84±1,97 x 106 células CD34+/ kg. La tasa de éxito de movilización fue del 53,9% (IC 95%, 39,5% a 67,8%) en la población ITT y el 62,2% (IC 95%, 46,5% a 76,2%), en los 45 pacientes de la población PP. La movilización fue considerada efectiva por los investigadores en el 80,8% de los pacientes de la población ITT y el 88,9% de aquellos en la población PP. Conclusión: A pesar de su naturaleza observacional, este estudio sugiere que Filgrastine está asociado con las tasas de éxito esperadas en la recolección de CPSP para trasplante autólogo de médula ósea. Introduction: Filgrastim, which plays a key role in peripheral-blood progenitor cell (PBPC) harvesting, has been available for nearly 25years, and several filgrastim biosimilars are available. Objective: We assessed whether a biosimilar filgrastim (Filgrastine®) was associatedwith effective mobilization in patients undergoing PBPC harvest for autologous transplantation. Method: We reviewed the charts ofpatients with multiple myeloma and lymphomas treated at three institutions in Brazil. The primary outcome (mobilization success rate,MSR) was the proportion of patients in the intention-to-treat (ITT ) population in whom at least 2 x 106 CD34+cells/Kg were harvestedby leukapheresis on days 5 and/or 6. The per-protocol (PP) population comprised patients who received at least 4 days of Filgrastine andhad at least one CD34+ count on Days 5 or 6. Results: The daily dose of Filgrastine (on D1, with few changes thereafter) ranged from8.5 to 28.9 mcg/Kg in the 52 patients in the ITT population, with a median of 13.8 mcg/Kg; 51 patients received at least four doses. Amean of 2.84±1.97 x 106 CD34+cells/Kg were harvested. The MSR was 53.9% (95% CI, 39.5% to 67.8%) in the ITT population and62.2% (95% CI, 46.5% to 76.2%) in the 45 patients in the PP population. The mobilization was considered effective by investigators in80.8% of patients in the ITT population and 88.9% of those in the PP population. Conclusion: Despite its observational nature, thisstudy suggests that Filgrastine® is associated with the expected success rates in PBPC harvest for autologous transplantation.

Objective: To assess clinical outcomes of intolerant, relapsed or refractory patients who could not be treated with new tyrosine kinase inhibitors or experimental therapies. Methods: A retrospective cohort of 90 chronic myeloid leukemia patients in all phases of the disease treated with imatinib mesylate as their first TKI therapy, and with dasatinib or nilotinib as the next line of therapy. We evaluated clinical outcomes of these patients, with special focus on the group that needed more than two therapy lines. Results: Thirty-nine percent of patients were refractory or intolerant to imatinib. An 8-year overall survival rate of the patients who went through three or more lines of treatment was significantly lower, compared to those who were able to maintain imatinib as their first-line therapy (83% and 22%, respectively p

Chronic lymphocytic leukemia (CLL), a disorder for which B cell heterogeneity and increased cellular proliferation play central pathogenic roles, displays several genetic abnormalities that are associated with poor prognosis and have therapeutic implications. In this review, we discuss the prognostic role and therapeutic implications of chromosome 17p deletions and TP53 mutations in CLL. Unlike other recurrent genetic abnormalities, the frequency of TP53 alterations is relatively low in newly diagnosed patients, but increases sharply with disease progression, which suggests that these alterations represent an evolutionary mechanism of resistance. In comparison with patients without such abnormalities, those with 17p deletions and TP53 mutations have lower response rates and more aggressive disease. One important consequence of the diverse molecular mechanisms that affect the TP53 pathway is the need to assess both the presence of 17p deletion and TP53 mutations before treatment initiation. Several authors have attempted to incorporate TP53 abnormalities in different prognostic models for CLL, and the recent International Prognostic Index for Chronic Lymphocytic Leukemia formally considers patients with TP53 abnormalities (deletion 17p or TP53 mutation or both) as high-risk. Several novel agents may improve results in patients with CLL, including in those with TP53 mutations. Ibrutinib, idelalisib, and venetoclax have been approved in various settings and countries for treatment of CLL. Further progress in targeted therapy and judicious use of chemotherapy, monoclonal antibodies, and reduced-intensity allogeneic transplantation will provide patients with CLL in general, and those with TP53 abnormalities in particular, with a better prognosis.

7514 Background: Relapse is expected in treated indolent lymphoma patients, and an unmet need exists to prolong remission with effective therapies. Lenalidomide + rituximab (R2) may improve the efficacy of next treatment by their unique mechanisms. Methods: The AUGMENT phase III study evaluated patients with R/R FL gr 1-3a (82%) and MZL (18%) after ≥ 1 prior systemic therapy (not rituximab refractory). Randomization was 1:1 to R2 (lenalidomide PO 20 mg/d, d1-21/28 X12 cycles [c] + rituximab [R] IV 375 mg/m2/wk, c1, d1, 8, 15, 22 and c2-5, d1) and R/placebo (same dosing schedule). The primary endpoint was PFS by 2007 IWG; secondary/exploratory analyses were time to next antilymphoma/chemotherapy treatment (TTNLT/TTNCT) and response to next treatment. Per regulatory guidance, PFS2 was defined as time from randomization to first PD or death from any cause after next antilymphoma treatment, or initiation of a third antilymphoma treatment. Results: Median PFS was superior for R2 over R/placebo (39.4 vs 14.1 mo; HR = 0.46; P < 0.0001). As of 22June2018, median TTNLT, TTNCT, and PFS2 were not reached for R2, and were significantly longer than R/placebo (HR = 0.54, 0.50, and 0.52, respectively). For 49/178 (28%) R2 and 80/180 (44%) R/placebo patients receiving next antilymphoma therapy, response was generally higher with R2 (57% ORR; 31% CR) than R/placebo (36% ORR; 16% CR; Table). Conclusions: These analyses suggest that R2 (vs R/placebo) prolonged time to subsequent treatment and is associated with longer PFS2, enabling greater response to next therapy. Although patient numbers were modest, it is hypothesized that patients who received R2 were generally more sensitive to subsequent therapy than those treated with R/placebo. Clinical trial information: NCT01938001. [Table: see text]

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 Results: A total of 445 patients were analyzed (Glivec=285; Generic=160). The median age was 54 years (18-87) in Glivec and 50 (18-89) in the Generic group (P=0.027). Sokal score stratification in Glivec and generic groups, was respectively: low risk 14.4%/25.7%; intermediate risk 42.3%/38.2% and high risk 43.3%/36.1% (P=0.02). B3a2 frequency was 51.5% vs. 37.7% in Glivec and Generic group, respectively, and b2a2 41.4% vs. 53.8% (P=0.017). There was no significant difference in gender, Hasford, EUTOS scores and ECOG. The median follow-up was 25 months (0-71) and 11 months (0-31) for Glivec and Generic groups, respectively (P Conclusion: The group treated with generic imatinib presented higher rate of failure at 3 months and lower OS, PFS and EFS at 24 months. Differences between the groups included a longer time to initiate treatment in the Generic group, a higher proportion of patients with b2a2 transcripts, which were related to an inferior rate of molecular responses and survival in other studies. There was no difference in the safety profile. The long-term impact in prognosis will be evaluated after a longer follow-up. Disclosures Pagnano: Shire: Other: Lecture; Abbvie: Consultancy; EMS: Other: Financial support for participation in congress; Novartis: Consultancy. Magalhaes:Novartis: Consultancy, Other: Lecture. Clementino:EMS: Other: Financial support for congress. Gaidano:AbbVie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Morphosys: Honoraria; Amgen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Centrone:EMS: Other: Financial support for congress, Speakers Bureau; Bristol Meiers-Squibb: Other: Financial support for congress, Speakers Bureau; Novartis: Other: Financial support for congress, Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Other: Financial support for congress, Speakers Bureau. Fogliatto:Novartis: Consultancy; Roche: Consultancy, Speakers Bureau; Janssen: Honoraria, Research Funding. Giai:Pfizer: Consultancy; Novartis: Consultancy. Bortolheiro:Abbvie: Consultancy, Speakers Bureau; Sanoffi: Speakers Bureau; Novartis: Consultancy, Speakers Bureau.

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.

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.

Variant Philadelphia (Ph) chromosome can be observed in 5-10 % of chronic myelogenous leukemia (CML) patients. However, there are only a few studies which have analyzed the prognostic implications of these complex translocations in CML patients after the advent of imatinib mesylate and the results found are conflicting. We investigated the clinical features and cytogenetic response of Brazilian chronic phase (CP) CML patients with variant Ph treated with imatinib mesylate. Among 93 CP CML patients, eight (8.6 %) exhibited complex translocations, involving one (n = 6), two (n = 1), or three (n = 1) additional chromosomes. At 6, 12, and 18 months, a complete cytogenetic response was observed in 100 % of variant Ph patients, respectively. No significant difference was found between variant Ph and standard translocation patients regarding the response to IM treatment at 6, 12, and 18 months. Likewise, there was no statistically significant difference between the two groups concerning the overall survival, failure-free survival, progression-free survival, and event-free survival. The results obtained in our study, despite our sample size, suggest, in agreement to other data found in the literature, that the presence of variant Philadelphia chromosome does not bestow a prognostic disadvantage when compared to the group with classic Ph. This observation does not suggest the need to adjust the treatment protocol due to the presence of variant Ph. However, further studies with larger sample sizes and evaluating both the cytogenetic and molecular response to IM treatment should be conducted to confirm our findings.

Treatment of chronic myeloid leukemia with BCR-ABL tyrosine kinase inhibitors requires full adherence in order to maximize the likelihood of achieving optimal responses, and to minimize healthcare costs. In this article, we review some of the methods available for assessing compliance, the main consequences of nonadherence on treatment outcomes, major factors commonly associated with poor compliance, a few successful measures for improving adherence and the most accepted recommendations for proactively managing adverse events.© 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

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.

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.

The aim of the present study was to assess the influence of socioeconomic status (SeS) on the outcome of allo-SCT at a Brazilian SCT center. In total, 201 patients receiving HLA-identical related allo-SCTs were studied. The median age was 30 years. Overall, 163 patients had malignancies (CML 68, ALL/AML 63, myelodysplastic syndrome 12 and others 20). SeS was defined according to the Brazilian Association of Market Research Agencies classification, where people are clustered in groups A-E (richest to poorest). In total, 146 patients (72%) were classified as richest (A+B+C) and 55 (28%) as poorest (D+E). The D+E SeS group was associated with a higher incidence of chronic GVHD and acute GVHD (hazard ratio (HR)=2.61; P=0.001 and HR=2.62; P=0.001, respectively), better platelet and neutrophil engraftment (HR=1.94; P=

Imatinib mesylate (IM) is now first-line treatment for CML. To study the results of treatment with IM after IFN failure/intolerance versus allogeneic BMT (allo-BMT), we retrospectively analyzed 264 patients treated for CML in first chronic phase in three different institutions. Over a 6-year period (2001–2006), 174 patients received IM after failure of or intolerance to IFN. During the same period of time, 90 patients received an allo-BMT from an HLA-matched sibling (n=83) or an unrelated donor (n=7). The IM group was older (41 versus 33 years, P

Background Monitoring response to TKI therapy is one of the key management strategies of chronic myeloid leukemia (CML). Early molecular response to first-line TKI therapy is emerging as an effective prognostic factor indicator of long-term durable response and survival. Objectives We conducted a study to evaluate the importance of the early molecular response (EMR) at 3, 6 and 12 months (mo), and 3-year event free survival (EFS). Methods This is a retrospective study in a cohort of pts with chronic myeloid leukemia chronic phase (CP) enrolled in 14 Hematology centers in South Brazil. All pts received imatinib 400mg as first or second-line therapy. Patient evaluation and response criteria followed the ELN recommendations. EFS was measured from the start of imatinib to the date of any of the following events while on therapy: death from any cause, loss of complete hematologic response, loss of complete cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, or progression to accelerated phase or blastic phase. Results We analyzed data from 517 pts with CML-CP diagnosed since 1990. After a median observation time of 46 months, 5-year overall survival (OS) was 86% and 5-year event-free-survival was 53%. At 3 mo, EFS was 72,5% for 46 pts with BCR-ABLIS ≤10% compared to 58% for 14 pts with BCR-ABLIS >10% (p1% (p0,1% (p Conclusions A significant proportion of pts achieve ERM after 3,6 and 12 mo of imatinib therapy with better 3-year EFS. ERM may could identify those pts more likely to have a favorable outcome. Disclosures No relevant conflicts of interest to declare.

Sustained deep molecular response (MR4.5) after imatinib treatment defines a subgroup of patients with chronic myeloid leukemia (CML) with better outcome and that probably would be able to stop treatment in the future, according to results of clinical TKI discontinuation trials. Most of these trials showed that patients with a long-term imatinib treatment and low Sokal risk have a higher probability of maintain a deep molecular remission after stopping treatment. OBJECTIVES The main objective is to review the molecular responses, overall survival and event free survival of CP CML patients that have been treated with imatinib in 14 hematology centers in South Brazil. Using our data basis we also would like to see how many of them present long-term imatinib treatment, sustained deep molecular remission and correlate these findings with the Sokal risk groups. These data would allow us to predict patient profile that could be able to discontinue the treatment in the future in a prospective clinical trial. PATIENTS AND METHODS This is a retrospective study in a cohort of pts with chronic myeloid leukemia chronic phase (CP) that have been treated in 14 hematology centers in South Brazil. All pts received imatinib 400mg as first or second-line therapy. Patient evaluation and response criteria followed the ELN recommendations. MR(4.5) was defined as ≥ 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction. All tests were performed at a central standardized according to ELN. Event-free-survival (EFS) was measured from the start of imatinib to the date of any of the following events while on therapy: death from any cause, loss of complete hematologic response, loss of complete cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, or progression to accelerated phase or blastic phase. Overall survival (OS) was measured from the start of imatinib until death of any cause or to the date patient was last known to be alive. RESULTS Data from 474 patients was analyzed. After a median observation time of 46 months, 5-year overall survival (OS) was 86%, 5-year event-free-survival was 53%. Of the 474 patients, 258 had adequate PCR evaluations during treatment. 118 of 258 (45,7%) patients achieved MR(4.5) and 69 of 258 (27%) had sustained response for at least two years after a minimum time of treatment of 3 years. The cumulative incidence of MR(4.5) after 9 years was 76% (median, 3 years). In the group that achieved MR(4.5), there was only 1 (0,8%) death and 1 (1,1%) progression compared to 8 deaths (5,7%) and 8 progressions (7,5%) in the group without MR(4.5); these differences were significant with p=0,03 and 0,02 respectively. In the subgroup of 69 patients that had had been treated with imatinib for 3 year or more and sustained deep response (RM4,5) for at least two years, 21 pts had low Sokal risk, 7 pts intermediate Sokal risk and only 4 pts a high Sokal risk. Unfortunately, in 37 pts the Sokal risk could not be accessed due to missing information. CONCLUSION In our series MR(4.5) is reached in the majority of patients with long-term imatinib treatment. MR(4.5) is a predictor of outcome with only one disease progression and one death due to CML in this group of patients. Unfortunatly PCR are not available for all patients in our clinical practice, but this situation are improving. Regarding the 69 patients with TKI discontinuation trial criteria, we find out that 21 patients fulfill such criteria. In the future, according to the results of current stop trials it could be possible include this selected group of CP CML patients in a prospective clinical trial. Disclosures No relevant conflicts of interest to declare.

Background Polycythemia vera (PV) is a subgroup of myeloproliferative neoplasm (MPN) BCL-ABL1 negative. The current therapy of PV should be aimed at preventing vascular complications and avoid increasing the risk of leukemic transformation. The therapy response monitoring is based in the European LeukemiaNet (ELN) unified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera consensus process, published by Barbui T et al in Br J Haematol 2010;148(6):961-963. Objectives We conducted a study to assess in our clinical practice the aplicability of the standard criteria for resistance and intolerance proposed by ELN in patients (pts) with PV that have been treated with hydroxycarbamida (HU). Methods This is a retrospective study in a cohort of pts with PV enrolled in a single Hematology University center in South Brazil. All pts were treated according to PV guidelines, and the response monitoring was based on clinical practice. All database was compared to standard criteria proposed by ELN. Intolerance /resistance was defined by: a) need for phlebotomy to keep hematocrit < 45% after 3 months of at least 2 g/d of HU or b) uncontrolled myeloproliferation (ie, platelet count > 400 x109/L and white blood count (WBC) > 10 x109/L) after 3 months of at least 2g/d of HU or c) failure to reduce massive splenomegaly by 50% as measured by palpation or failure to completely relieve symptoms related to splenomegaly after 3 months of at least 2 g/d of HU or d) absolute neutrophil count < 1.0 x109/L or platelet count < 100 x109/L or hemoglobin < 10 g/dL at the lowest dose of HU required to achieve a complete or partial clinicohematologic response or e) presence of leg ulcers or other unacceptable HU related nonhematologic toxicities, such as mucocutaneous manifestations, GI symptoms, pneumonitis or fever at any dose of HU. Results We analyzed data from 33 patients with PV assisted in the last five years in our outpatient clinical data. The ELN criteria for resistance and intolerance were accessed in these patients. At diagnosis, 42,4% of pts were younger than 61yo, and 54,5 were male. Arterial hypertension, diabetes mellitus and dyslipidemia were identified on 21, 2 and 7 pts, respectively. Only one patient was tobacco smoker at diagnosis. Total of 5 pts showed WBC > 15 x109/L, and 7 pts showed platelets > 450 x109/L. Massive splenomegaly is a rare PV manifestation in our series, occurring in 2 pts. Five patients complained of symptoms related to PV as pruritus and vasomotor phenomena at diagnosis. Less than 5% of patients had been treated with 2 g of HU for more than 3 months. In daily practice, when the patient presented hematologic toxicity, the HU was decreased and, if the hematocrit was over 45%, an occasional phlebotomy was performed. In relation to platelets (less than 400 x 109/L) and leucocyte (less than 10 x109/L) counts, these targets were not used exclusively in the clinical practice to change treatment. The intolerance was easily discriminated in patients with leg ulcers and other non-hematological events. Conclusion These criteria were done based on an expertise consensus for international criteria standardization for clinical studies. Its application in a retrospective study, using clinical daily practice data is not adequate. The reason is that in the last years the main target to treat patients was the hematocrit above 45%, the exact number of platelets and leucocytes is still not a consensus to define resistance, so different counts had been used to guide treatment, we rarely used HU doses above 1500 mg/daily to treat our patients and massive splenomegaly was observed in very few patients. These criteria should be used most for prospective studies. Disclosures No relevant conflicts of interest to declare.

Reports on treatment outcomes in adults with acute lymphoblastic leukemia (ALL) in Brazil are sparse. To evaluate the outcome of patients with ALL managed by the public healthcare system, we studied 42 adults treated from 1990 to 1997 in the Division of Hematology at Hospital de Clínicas, Porto Alegre, Brazil. Of these patients, 14/42 were females and their median age at diagnosis was 26 (17–64) years. The diagnosis of ALL was based on cytological examination of marrow smears, and immunophenotypic and cytogenetic studies, when available. Fifty percent of the patients expressed CD10, 30% were CD10 negative and CD19 positive and 20% expressed T markers. Philadelphia chromosome was found in 4 (7.14%). The chemotherapy protocol was adapted from the German Multicenter ALL (GMALL) 02-84 protocol. The complete remission rate was 93% and the overall survival at 5 years was 41%. No particular risk factor was identified in our series. These results are comparable to the findings of other international studies.

Background Treatment of chronic myeloid leukemia with imatinib leads to disease remission in a majority of patients (pts), but in a subgroup of pts controlling the disease remains a challenge. One of the proposed prognostic factors for identifying this subset of pts is the treatment response in the first months of imatinib therapy. The definitions of response, warning signs and failure to treatment, with the identification of pts at greater risk of progression or failure, were revised and published in 2013 by the European Leukemia Net group. Aims To apply the new recomendations of ELN2013 in order to verify the evolution of the patients according to the response criteria at 12 months (mo) of imatinib therapy. Methods Retrospective study in a cohort of patients with CP-CML from a southern Brazilian database. All patients received imatinib 400mg as first or second-line therapy. Patient evaluation and response criteria followed the ELN2013 criteria and were classified in 3 groups according to the cytogenetic and molecular responses at 12 mo: optimal, warning and failure. An event was defined as any of the following while on therapy: death from any cause, loss of complete hematologic response, loss of complete cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, or progression to accelerated phase or blastic phase. Results Data from 98 pts with a median follow-up (FU) time of 40 mo was analysed. At 12 mo of imatinib therapy, 35 pts (36%) had optimal response according to the ELN2013 criteria. 26 (26,5%) were classified as warning and 37 (37,5%) as failure. Within the pts with optimal response, only 4 (11%) have had any event, with a median time-to-event (TTE) of 36 mo; in the warning group the event rate and TTE were 3 (12%) and 28 mo, respectively. There were no significant differences in the results between these two groups. On the other hand, within the pts with failure, 24 (65%) presented an event during FU with a TTE of 19 mo. This difference was significant compared to the two previous groups. Interestingly, within the warning group, 12 pts (46%) developed major molecular response (MMR) at any point during FU, while only 12 (32%) pts achieved RMM in the failure group. Conclusion In this cohort of CP-CML pts is established the diference in the event rate between the pts who achieve optimal or warning responses at 12 mo of imatinib treatment when compared with those with failure criteria, according to the new ELN2013 recomendations. Despite having some late responders, atention must be paid in pts in the failure group as they are in greater risk of progression or failure. As demonstrated in this analysis, the ELN2013 criteria can be applied in this population in the clinical practice. Disclosures: No relevant conflicts of interest to declare.

Lack of imatinib-induced thyroid dysfunction in a cohort of non-thyroidectomized patients Jose Miguel Dora, Murilo Anderson Leie, Bruno Netto, Laura Maria Fogliatto, Lucia Silla, Felipe Torres and Ana Luiza Maia Endocrine Division, Thyroid Section, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, Hematology Division and Radiology Division, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil

Abstract 4423 Background Treatment of chronic myeloid leukemia with imatinib leads to disease remission in a majority of patient, but in some patients (pts) controlling the disease remains a challenge. One of the proposed prognostic factors for identifying this subset of pts is the treatment response in the first months of therapy. Objectives We conducted a study to evaluate the importance of the early complete cytogenetic response (CCyR) and the factors associated with its achievement. Methods This is a retrospective study in a cohort of pts with chronic-phase chronic myeloid leukemia (CP-CML) enrolled in 14 Hematology centers in South Brazil. All pts received imatinib 400mg as first or second-line therapy. Early-imatinib treatment was considered when imatinib started before 12 months (mo) from diagnosis. Patient evaluation and response criteria followed the ELN recommendations. The ACE-27 (Adult Comorbidity Evaluation-27) is a 27 item comorbidity index for patients with cancer and assign weights from 1 to 3 based on the dysfunction grade of each condition (mild, moderate and severe, respectively). An ACE-27 score was applied to each patient. Imatinib suspensions were considered if superior to 20 days at any point during therapy. EFS was measured from the start of imatinib to the date of any of the following events while on therapy: death from any cause, loss of complete hematologic response, loss of complete cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, or progression to accelerated phase or blastic phase. Results We analyzed data from 450 pts with CP-CML diagnosed since 1990. The median age at diagnosis was 48 yr (4 – 85) and 55% were male. The median time from diagnosis to imatinib was 7 mo (0 – 178) and 71% pts were early-imatinib treated. Prior therapy with interferon was used in 60% pts. The median of follow-up was 47 mo. With 6 months of imatinib therapy, 198 pts (44%) achieved CCyR. In this group, the four year cumulative incidence of events was 33 (17%) and the EFS was 75,5%. 252 (56%) were not in CCyR at 6 months of therapy. In this group, a greater proportion of cumulative of events was observed: 86 (34%), and the EFS was 62,3%. This difference was significant (P=0,03; Figure 1). In this group of pts, 63% achieved CCyR after 6 months any time during follow up and the median time for CCyR in these pts was 17 months. The chance of achieving major molecular response (MMR) during follow up was 79% for the pts with CCyR at 6 months compared to 53% for the group with no CCyR at 6 months (P Conclusions A great proportion of pts achieve CCyR after 6 months of imatinib therapy, nevertheless, the pts who achieve CCyR by 6 months of therapy have greater proportion of major molecular response and event-free survival. Imatinib therapy should be started as soon as possible and additional efforts must be taken to avoid nonadherence. Finally, special attention should be given to pts with comorbidities as their results tend to be worse. Disclosures: No relevant conflicts of interest to declare.

Abstract 4425 Adherence to imatinib therapy has proven to be a major determinant of treatment results, but the degree of impact and the determinants of nonadherence are still contradictory. There is no information regarding adherence to imatinib therapy in the Brazilian public health system. The aims of this study were to identify the characteristics related to treatment interruptions and nonadherence and to examine how these interruptions affect treatment responses and survival. Materials and Methods We conducted a retrospective study in a cohort of patients (pts) with CP-CML enrolled in 14 Hematology centers in South Brazil. All pts received imatinib 400mg as first or second-line therapy. Early-imatinib treatment was considered when imatinib started before 12 months (mo) from diagnosis. Patient evaluation and response criteria followed the ELN recommendations. The ACE-27 (Adult Comorbidity Evaluation-27) is a 27 item comorbidity index for patients with cancer and assign weights from 1 to 3 based on the dysfunction grade of each condition (mild, moderate and severe, respectively). An ACE-27 score was applied to each patient. Imatinib suspensions were considered if superior to 20 days at any point during therapy. Two levels of analysis were performed: all kinds of interruptions (nonadherence and toxicity) and only nonadherence ones. Information for nonadherence was taken from medical and pharmacy registers (pt self-report, missing scheduled appointments and pill counts). Results We analyzed data from 185 pts with CP-CML diagnosed since 1990. The median age at diagnosis was 48 yr (4 – 85) and 55% were male. The median time from diagnosis to imatinib was 7 mo (0 – 178) and 71% pts were early-imatinib treated. Prior therapy with interferon was used in 70% pts. The median of follow-up was 47 mo. Treatment interruption was observed in 63/185 patients (34%) and was related to toxicities in 35/63 pts (55%) and to nonadherence in 28/63 pts (45%). The adherence rate was 85%. In a multivariate analysis, only late-onset imatinib treatment (Odds Ratio [OR]=36,05; p Conclusions In this cohort, a substantial proportion of pts failed to take imatinib properly, decreasing the chances of disease control. The late onset of imatinib therapy correlates with lower adherence, so front-line imatinib therapy should be started as soon as possible. Special attention should be given to pts with severe comorbidities, as they are more prone to suffer side effects or to lack adherence. Finally, pts who interrupted treatment had lower CCyR, MMR and EFS. Clinical and patient characteristics related to nonadherence Disclosures: No relevant conflicts of interest to declare.

Abstract 4487 Background: Imatinib treatment for Chronic Myeloid Leukemia (CML) was first introduced in Brazil in 2001, initially used as second line therapy for patients resistant or intolerant to interferon (IFN). In 2008 imatinib was adopted as front-line therapy for chronic-phase (CP-CML) and clinical experience is improving since then, but little is known about the result of its introduction in our clinical practice. Aims: To evaluate the impact of imatinib treatment in the outcomes of a cohort of CP-CML and the prognostic significance of Sokal and Hasford scores and late-onset treatment. Methods: We conducted a retrospective study in a cohort of patients with CP-CML from a south Brazilian database. All patients received imatinib 400mg as first or second-line therapy. Patient evaluation and response criteria followed the European LeukemiaNet. The outcomes were response to treatment, event-free survival (EFS) and overall survival (OS). Results: We analyzed data from 185 pts with CP-CML diagnosed since 1990. The median age at diagnosis was 48 years (4 – 85). The median time from diagnosis to imatinib was 7 months (0 – 178) and 29% of pts had more than 12 months lapse. Prior therapy with IFN was used in 70% pts. All pts had a minimum follow-up of 12 months. At baseline, 57 pts (31%) were in complete hematological response (CHR) due to the use of previous treatment. Of the 127 pts not in CHR at baseline, 98% achieved CHR early during imatinib treatment. 177 pts had cytogenetic evaluation during treatment and 9 pts were in complete cytogenetic response (CCyR) due to the use of previous IFN. Of the 168 pts not in CCyR at baseline, 86,4% achieved a major cytogenetic response (MCyR) during imatinib treatment (84% had a CCyR and 2,4% had a partial cytogenetic response). The rate of pts achieving MCyR any point during treatment differed significantly in the low, intermediate and high risk Sokal score groups (97%, 81% and 78% respectively, P=0,04), but not in the Hasford score groups (90%, 85% and 72%, P=0,22). Minor cytogenetic response was seen in 3,6% of pts, minimal cytogenetic response in 6% and 9,5% had no cytogenetic response. The median time to a MCyR was 9 months, with 62% of pts achieving MCyR at 12 months. The rate of pts achieving MCyR in 12 months differed significantly between pts who start imatinib before 12 months from diagnosis (68%) and those late treated (47%, P=0,02). Evaluation of minimal residual disease at the molecular level was available for 155 pts: 25,5% of pts had a complete molecular response (CMR), 43% had a major molecular response (MMR) and 2 pts were in MMR at baseline due to previous IFN. The projected EFS and OS rates at 4 years were, respectively, 68% and 92% after a median follow-up time of 4 years. The rate of EFS differed significantly in the low, intermediate and high risk Sokal score groups (80%, 66% and 52% respectively, P=0,04), but not in the Hasford score groups (78%, 62% and 44%, P=0,09). During treatment with imatinib, 120 pts (65%) had a register of any grade hematologic adverse event (21% being grades 3 or 4) and 165 pts (90%) had a register of any grade nonhematologic adverse event (9,3% being grades 3 or 4). Of the 185 pts who received treatment, 134 (72%) continue to receive imatinib and 51 (28%) discontinued treatment. The reasons for discontinuation were: 11 (6%) pts had drug-related adverse events (3 [1,6%] hematologic and 8 [4,3%] nonhematologic), 17 (9,2%) had disease progression (5 [2,7%] loss of CHR, 10 [5,4%] loss of CCyR, 2 [1%] had progression to accelerate or blastic phase), 22 (11,9%) had treatment failure (3 [1,6%] had no CHR, 13 [7%] had no CCyR and 6 [3,2%] had no MMR), 1 pt (0,5%) discontinued due to comorbidity. For the 51 (100%) pts that discontinued imatinib, 31 (61%) switched to dasatinib, 17 (33%) to nilotinib, 1 (2%) to hydroxyurea, 1 (2%) to other treatment and 1 (2%) remained without treatment. Sixteen pts (8,6%) died during imatinib treatment or during long-term follow-up after discontinuation of imatinib. Conclusions: In our population of CP-CML pts treated with imatinib, a majority of patients achieved complete cytogenetic and major molecular responses, with a prolonged of OS and EFS and good safety profile. Sokal score showed better prognosis prediction than Hasford. Early onset of imatinib therapy led to better outcomes and justifies imatinib as front-line treatment of our patients. Disclosures: No relevant conflicts of interest to declare.