ALBERT

Description: Introduction: Asciminib, unlike all approved TKIs that bind to the ATP site of the BCR-ABL1 oncoprotein, is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor with a new mechanism of action. BOS, an ATP-competitive TKI, has shown clinical efficacy in pts who received ≥2 TKIs and in newly diagnosed CML, in prospective clinical trials. We asked if asciminib could provide superior efficacy to BOS beyond 2nd line, based on the clinical activity of asciminib monotherapy in heavily pretreated pts with CML in a phase 1 study. Methods: Adults with CML-CP previously treated with ≥2 TKIs were randomized 2:1 to asciminib 40 mg twice daily (BID) or BOS 500 mg once daily (QD). Randomization was stratified by major cytogenetic response (MCyR; Ph+ metaphases ≤35%) status at baseline. Pts intolerant of their most recent TKI were eligible if they had BCR-ABL1IS 〉0.1% at screening (19 pts with BCR-ABL1IS 10% or Ph+ 〉65% after 6 months of therapy (asciminib 10.8%, BOS 25.0%). Among the 24 pts who discontinued BOS due to lack of efficacy, 22 switched to asciminib. At baseline, ≥1 BCR-ABL1 mutation was present in 12.7% pts on asciminib (most common: F359C/V) and 17.1% on BOS (most common: M244V, F317L). Median duration of follow-up was 14.9 months from randomization to cutoff. Median duration of exposure was 43.4 wks (range, 0.1-129.9) for asciminib and 29.2 wks (range, 1.0-117.0) for BOS; median relative dose intensity was 99.7% (87-100) and 95.4% (74-100). MMR rate at 24 wks was 25.5% with asciminib and 13.2% with BOS, meeting the primary objective. The between-arm common treatment difference for MMR at 24 wks, after adjustment for MCyR status at baseline, was 12.2% (95% CI, 2.19-22.3: 2-sided P=.029). Among those pts who achieved MMR, median time to MMR was 12.7 wks and 14.3 wks with asciminib and BOS, respectively. At 24 wks, more pts on asciminib (17 [10.8%] and 14 [8.9%]) than on BOS (4 [5.3%] and 1 [1.3%]) achieved deep molecular response (MR4 and MR4.5, respectively). CCyR rate at 24 wks was 40.8% with asciminib vs 24.2% with BOS. Preplanned subgroup analysis showed that the MMR rate at 24 wks was superior with asciminib than BOS across most major demographic and prognostic subgroups, including in pts who received ≥3 prior TKIs, in those who discontinued the prior TKI due to treatment failure, and regardless of baseline cytogenetic response (Figure). Grade ≥3 adverse events (AEs) occurred in 50.6% and 60.5% of pts receiving asciminib and BOS, respectively. The proportion of pts who discontinued treatment due to AEs was lower with asciminib (5.8%) than BOS (21.1%). Grade ≥3 AEs and AEs requiring dose interruption and/or adjustments were reported less frequently with asciminib than BOS (Table 2). Most frequent grade ≥3 AEs (occurring in 〉10% of pts in any treatment arm) with asciminib vs BOS were thrombocytopenia (17.3%; 6.6%), neutropenia (14.7%; 11.8%), diarrhea (0%, 10.5%), and increased alanine aminotransferase (0.6%, 14.5%). On-treatment deaths occurred in 2 pts (1.3%) on asciminib (ischemic stroke and arterial embolism, 1 pt each) and 1 pt (1.3%) on BOS (septic shock). Conclusions: In this first controlled study comparing treatments for resistant/intolerant (R/I) pts with CML, asciminib, a first-in-class STAMP inhibitor, demonstrated statistically significant and clinically meaningful superiority in efficacy compared with BOS (primary objective), deeper MR rates, and a favorable safety profile. These results support the use of asciminib as a new treatment option in CML, particularly in R/I pts who received ≥2 prior TKIs. Disclosures Hochhaus: Novartis: Research Funding; Incyte: Research Funding; Pfizer: Research Funding; Bristol Myers Squibb: Research Funding. Boquimpani:Novartis: Speakers Bureau. Rea:BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: 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. Minami:Pfizer Japan Inc.: Honoraria; Takeda: Honoraria; Bristol-Myers Squibb Company: Honoraria; Novartis Pharma KK: Honoraria. Lomaia:Bristol Myers Squibb: Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Voloshin:Novartis: Honoraria, Speakers Bureau. Turkina:Pfizer: Honoraria; Novartis Pharma: Honoraria; BMS: Honoraria. Kim:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; ILYANG: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Sun Pharma.: Research Funding. Apperley:Bristol Myers Squibb: Honoraria, Speakers Bureau; Incyte: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau. Cortes:Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BioPath Holdings: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Telios: Research Funding; Astellas: Research Funding; Amphivena Therapeutics: Research Funding; Arog: Research Funding; BiolineRx: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Immunogen: Research Funding; Merus: Research Funding; Sun Pharma: Research Funding. Abdo:Novartis: Honoraria; Takeda: Honoraria. Kim:Paladin: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Research Funding. le Coutre:Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Saussele:Novartis: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria. Hughes:BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chee:Novartis: Other: Travel support for attendance at investigator meeting. García Gutiérrez:Novartis Pharma AG: Consultancy, Honoraria, Other: travel/accommodations/expenses, Research Funding; Pfizer: Honoraria, Other: travel/accommodations/expenses, Research Funding; Incyte: Consultancy, Honoraria, Other: travel/accommodations/expenses, Research Funding. Sasaki:Pfizer Japan: Consultancy; Otsuka: Honoraria; Novartis: Consultancy, Research Funding; Daiichi Sankyo: Consultancy. Aimone:Novartis: Current Employment. Allepuz:Novartis: Current Employment. Quenet:Novartis: Current Employment. Bédoucha:Novartis: Current Employment. Mauro:Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding; Novartis: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding; Pfizer: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding; Sun Pharma/SPARC: Research Funding.

Description: 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

Description: 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

Description: Introduction: No standard of care exists for patients (pts) with relapsed or refractory primary mediastinal B-cell lymphoma (rrPMBCL). As such, pts typically receive therapies recommended for diffuse large B-cell lymphoma, with poor prognosis. Similar to classical Hodgkin lymphoma, rrPMBCL tumors often overexpress the programmed death 1 (PD-1) ligands, PD-L1 and PD-L2. Data from the first full analysis of the phase 2 KEYNOTE (KN)-170 (NCT02576990) study showed that pembrolizumab provided effective and durable antitumor activity with a manageable safety profile in patients with rrPMBCL. These data led to the FDA approval of pembrolizumab for pts with rrPMBCL after ≥2 prior therapies. In this aggressive malignancy with few salvage options, duration of remission with PD-1 blockade remains a critical question. Here we present data from KN170 with an additional 24 months of follow-up in patients with rrPMBCL. Methods: Pts with rrPMBCL who had relapsed after or were ineligible for autologous stem cell transplant with ≥2 lines of prior therapy were enrolled in KN170 to receive 200 mg pembrolizumab IV Q3W until disease progression or toxicity, for up to 2 years. Tumor response was assessed Q12W with PET/CT scans by IWG 2007 criteria. The primary endpoint was objective response rate (ORR) by blinded independent central review (BICR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory endpoints included response by Lugano 2014 criteria. The data cutoff date for this analysis was May 7, 2020. Results: At the data cutoff date, among all treated pts (N=53), 13 had completed 2 years of treatment and 40 had discontinued largely due to progression (n=30). The ORR was 45% (24/53; 95% CI 32-60) with a CR rate of 19% (10/53; 13/53 [25%] by Lugano criteria). No patient who achieved CR by BICR had received consolidation therapy or had progressed at data cutoff. After a median study follow-up of 43.1 months (range, 35.6-50.7) the median DOR was not reached (range, 1.1+ to 46.9+ mo); 76% of pts had a response duration ≥36 mo. Median PFS was 5.5 mo (95% CI, 2.7-15.1), with 36-mo PFS rate of 34%. The median OS was 22.3 mo (95% CI, 7.3 to not reached) with 36-mo OS rate of 45%. At data cutoff, 50 (94%) pts had at least one adverse event (AE), with 30 (57%) having a treatment-related AE. The most common treatment-related AEs were neutropenia (19%), asthenia (9%), hypothyroidism (8%), fatigue (6%), and pyrexia (6%). Grade ≥3 treatment-related AEs occurred in 12 (23%) pts. Six (11%) pts had an immune-mediated AE. There were no treatment-related grade 5 events. Conclusion: Results from the longer-term follow-up of KN170, the largest prospective clinical trial in rrPMBCL, shows that pembrolizumab provides robust and durable antitumor activity with a manageable safety profile in patients with rrPMBCL. Disclosures Zinzani: 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; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, 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; Kyowa Kirin: Consultancy, Speakers Bureau; Immune Design: 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; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Celgene: 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; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sandoz: 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; 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; Incyte: 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; AbbVie: 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; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bouabdallah:Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria. Walewski:Roche: Consultancy, Honoraria, Other: travel expenses, Research Funding; GSK/Novartis: Research Funding; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy. Caballero:Gilead: Other: travel; Roche: Other: travel; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: travel; Kite: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: travel; BMS: Other: travel. Christian:Acerta: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Merck: Research Funding; Millenium: Research Funding; MorphoSys: Research Funding; F Hoffman-La Roche: Research Funding; Triphase: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; AstraZenica: Membership on an entity's Board of Directors or advisory committees. Özcan:Takeda: Honoraria, Other: travel, Research Funding; Roche: Other: travel, Research Funding; Bayer: Research Funding; Abbvie: Other: travel, Research Funding; Archigen: Research Funding; Celgene: Research Funding; MSD: Research Funding; Novartis: Research Funding; Amgen: Honoraria, Other: travel; BMS: Other; Jazz: Other; Sanofi: Other; Abdi Ibrahim: Other; Janssen: Other: travel, Research Funding. Salles:Bristol Myers Squibb: Consultancy, Other; Takeda: Consultancy, Honoraria, Other; Gilead: Consultancy, Honoraria, Other: Participation in educational events; Debiopharm: Consultancy; Kite: Consultancy, Honoraria, Other; MorphoSys: Consultancy, Honoraria, Other; Janssen: Consultancy, Honoraria, Other: Participation in educational events; Novartis: Consultancy, Honoraria, Other; F. Hoffman-La Roche Ltd: Consultancy, Honoraria, Other; Celgene: Consultancy, Honoraria, Other: Participation in educational events; Epizyme: Consultancy; Karyopharm: Consultancy; Autolus: Consultancy; Amgen: Honoraria, Other: Participation in educational events; Abbvie: Consultancy, Honoraria, Other: Participation in educational events; Genmab: Consultancy. Shipp:Celgene: Honoraria; Ono Pharmaceutical: Honoraria; Bayer: Honoraria; Bristol Myers Squibb: Consultancy, Research Funding; Merck: Research Funding. Thompson:Merck Sharp & Dohme Corp.: Current Employment. Orlowski:Merck Sharp & Dohme Corp.: Current Employment. Marinello:Merck & Co., Inc., Kenilworth, NJ, USA: Other: Stock ownership; Merck & Co., Inc.: Other: Travel, accommodations, expenses; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA: Current Employment. Armand:Pfizer: Consultancy; Merck & Co., Inc.: Consultancy, Honoraria, Research Funding; Adaptive: Consultancy, Research Funding; Affimed: Consultancy, Research Funding; Sigma Tau: Research Funding; Celgene: Consultancy; IGM: Research Funding; Otsuka: Research Funding; Tensha: Research Funding; Genentech: Research Funding; Infinity: Consultancy; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Roche: Research Funding.

Description: Introduction: Chronic lymphocytic leukemia (CLL) typically occurs in elderly patients and has a highly variable clinical course. It is important to understand the aspects that affect the outcomes of CLL in a real-world setting. Besides biological factors, other socioeconomic and health system factors may influence the clinical course of CLL. Hence, data from the Brazilian Registry of CLL was analyzed to compare clinical and treatment-related characteristics in patients with CLL treated in public or in private institutions in Brazil. Objective: To describe the outcomes of a series of CLL patients followed in public or in private hospitals in Brazil. Methods: The Brazilian Registry of CLL was started in 2004 as a prospective non-interventional data collection tool. Inclusion criteria for enrollment followed the IWCLL guidelines. For this analysis, we included all patients with minimum available data for analysis of patient and disease characteristics and survival. Results/discussion: From January 2004 to July 2020, 2927 patients from 37 centers met eligibility criteria for this analysis: 2324 (79%) were followed at public hospitals and 603 (21%) at private hospitals. The majority were male (57%), with median age of 65 years (ranging from 23 to 106). Binet stage was A in 1618 (58%) patients, B in 628 (23%) and C in 525 (19%). FISH for del(17p) was performed in only 479 patients (16%), while FISH for the most common aberrations [del(13q), +12, del(11q), and del(17p)] was performed in only 445 patients (15%). IGVH mutational status was performed in only 211 patients (7%), and karyotype in only 140 patients (5%). Comparing public and private hospitals, we observed that patients in public hospital are slightly older (median age 66 years vs. 64 years for private hospitals, P=0.04), had more advanced diseases at diagnosis (frequency of Binet B or C was 44% in public vs. 32% in private hospital, P