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In: Blood, American Society of Hematology, Vol. 136, No. 10 ( 2020-09-3), p. 1134-1143

Abstract: Given advanced age, comorbidities, and immune dysfunction, chronic lymphocytic leukemia (CLL) patients may be at particularly high risk of infection and poor outcomes related to coronavirus disease 2019 (COVID-19). Robust analysis of outcomes for CLL patients, particularly examining effects of baseline characteristics and CLL-directed therapy, is critical to optimally manage CLL patients through this evolving pandemic. CLL patients diagnosed with symptomatic COVID-19 across 43 international centers (n = 198) were included. Hospital admission occurred in 90%. Median age at COVID-19 diagnosis was 70.5 years. Median Cumulative Illness Rating Scale score was 8 (range, 4-32). Thirty-nine percent were treatment naive (“watch and wait”), while 61% had received ≥1 CLL-directed therapy (median, 2; range, 1-8). Ninety patients (45%) were receiving active CLL therapy at COVID-19 diagnosis, most commonly Bruton tyrosine kinase inhibitors (BTKi’s; n = 68/90 [76%]). At a median follow-up of 16 days, the overall case fatality rate was 33%, though 25% remain admitted. Watch-and-wait and treated cohorts had similar rates of admission (89% vs 90%), intensive care unit admission (35% vs 36%), intubation (33% vs 25%), and mortality (37% vs 32%). CLL-directed treatment with BTKi’s at COVID-19 diagnosis did not impact survival (case fatality rate, 34% vs 35%), though the BTKi was held during the COVID-19 course for most patients. These data suggest that the subgroup of CLL patients admitted with COVID-19, regardless of disease phase or treatment status, are at high risk of death. Future epidemiologic studies are needed to assess severe acute respiratory syndrome coronavirus 2 infection risk, these data should be validated independently, and randomized studies of BTKi’s in COVID-19 are needed to provide definitive evidence of benefit.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.2020006965

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. 18 ( 2021-11-04), p. 1768-1773

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.2021011841

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4414-4414

Abstract: Introduction: Given the availability of several active treatment (tx) options for CLL, providers frequently make tx recommendations based on their interpretation of objective data from consensus criteria and clinical trials. There are limited data describing patient (pt) experience, values, and insights when encountering multiple tx choices. The CLL Society, a pt-driven, physician-curated nonprofit organization focused on the unmet needs of the CLL community, sought to explore how CLL pts make tx decisions. Methods: A 64 question survey was distributed online and in paper to CLL pts from Oct-Dec 2017. The survey was developed by CLL experts. The research was IRB-approved. Chi square was used for statistical comparison; all other analyses are descriptive in nature. Results: 1147 pts from 48 states completed the survey. Median age was 65 (range 28-86), 46% male, 96% Caucasian. Who Influences Tx: Of the 79% of pts who have seen a CLL expert, defined as a provider focused on CLL at an academic/research center, 95% rated their provider as very/extremely influential. 83% of pts rated their own opinions as influential, and 59% rated the opinion of a general hematologist/oncologist (gen heme/onc), a provider who sees a variety of cancer types, as influential. Only 27% let their provider unilaterally decide on tx. Of these pts, 19% trusted their provider to select the best tx and 5% didn't have enough understanding to be involved in the decision. 64% were influenced by outside sources of information, such as family members, live CLL support groups, or online sources including pt experts and forums. Factors in Deciding Tx: Of the 67% pts surveyed who have been treated, 73% were offered 〉 1 tx choice by their provider. In deciding on a specific tx, 94% of respondents stated that it was very/extremely important to know there were tx options beyond their current regimen. The most important factors in selecting tx were response rate (91%), overall survival (88%), progression-free survival (86%), long-term side effects (82%), ability to achieve undetectable MRD (80%), cost/insurance coverage (66%), and location of tx (50%) with significant differences between subgroups (Table 1). Tx was impacted by cost or insurance issues for 16% (n=104). Of these 104 pts, cost/insurance issues resulted in tx delay for 34 and change in tx plan for 24 pts. 16 pts reported that an appeal led to coverage and 16 pts received financial assistance. Pts' willingness to accept potentially curable but high-risk tx was heavily influenced by availability of alternate options. For example, 18% of pts would be willing to consider cytotoxic chemotherapy if alternate options were available vs. 72% if no options were available. Similar patterns were seen with CAR-T tx (28% vs. 79%) and bone marrow transplantation (BMT) (15% vs. 66%) with significant differences between subgroups (Table 2). 82% were willing to take a life-long tx for long-term control without potential for cure. Willingness to accept long-term tx was significantly higher in treated vs. untreated pts (84% vs. 77%, p=.006) and men vs. women (84% vs. 78%, p=.008). Clinical Trial Education: Of those treated by a gen heme/onc, 31% received no education on clinical trials. Only 15% reported good understanding of trial opportunities vs. 52% treated by a CLL expert (p 〈 .001). 9% of pts treated by gen heme/onc were offered clinical trial participation vs. 47% treated by a CLL expert (p 〈 0.001). Pts who declined or would have declined participation cited reasons including preference for "proven" tx (38%), distance from trial site (29%), fear (20%), frequent imaging (20%), overall lack of understanding about trials (15%), and lack of information (14%). Summary: Most respondents want to be and are involved in tx decisions. While providers are influential in decision making, CLL pts also rely on outside sources. Gender, age, and tx status influence which factors drive decision making. Pts select tx based on response rate, survival, side effects, and ability to achieve deep response and want a plan in place for sequencing tx. The majority are willing to consider long-term tx without cure. Few want chemotherapy, CAR-T, or BMT unless they have no other options. A significant opportunity for improvement in education on clinical trial opportunities was identified. This description of pt experience, values, and preferences enriches the informed consent process and may lead to more tailored and patient-centered care. Disclosures Kennard: AbbVie, Gilead, Verastem: Consultancy. Furman:TG Therapeutics: Consultancy; Loxo Oncology: Consultancy; Sunesis: Consultancy; Verastem: Consultancy; Incyte: Consultancy, Other: DSMB; Genentech: Consultancy; Acerta: Consultancy, Research Funding; Gilead: Consultancy; Janssen: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; AbbVie: Consultancy. Pagel:Pharmacyclics, an AbbVie Company: Consultancy; Gilead: Consultancy. Davids:Sunesis: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; MEI Pharma: Consultancy, Research Funding; Surface Oncology: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Merck: Consultancy; Merck: Consultancy; MEI Pharma: Consultancy, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; MEI Pharma: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Research Funding; Surface Oncology: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Roche: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Verastem: Consultancy, Research Funding; BMS: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Surface Oncology: Research Funding; Verastem: Consultancy, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sunesis: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy; Roche: Consultancy. Nabhan:Cardinal Health: Employment, Equity Ownership. Kay:Acerta: Research Funding; Tolero Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios Pharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Infinity Pharm: Membership on an entity's Board of Directors or advisory committees; Cytomx Therapeutics: Membership on an entity's Board of Directors or advisory committees. Siddiqi:Juno Therapeutics: Other: Steering committee. Brander:Genentech: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Pharmacyclics, an AbbVie Company: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Teva: Consultancy, Honoraria; Novartis: Consultancy, Other: DSMB; TG Therapeutics: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; BeiGene: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Acerta: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; DTRM: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding. Wierda:AbbVie, Inc: Research Funding; Genentech: Research Funding. Hill:Abbvie: 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; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: 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; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cheson:AbbVie, Roche/Genentech, Pharmacyclics, Acerta, TG Therapeutics: Consultancy. Choi:Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Gilead: Speakers Bureau; Rigel: Consultancy; Genentech: Speakers Bureau; AbbVie, Inc: Consultancy, Speakers Bureau. Mato:AstraZeneca: Consultancy; Prime Oncology: Honoraria; Portola: Research Funding; Johnson & Johnson: Consultancy; Medscape: Honoraria; Celgene: Consultancy; TG Therapeutics: Consultancy, Research Funding; Acerta: Research Funding; Pharmacyclics, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Regeneron: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-112971

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4311-4311

Abstract: Introduction: Acalabrutinib (acala) is an irreversible, second generation Bruton tyrosine kinase inhibitor (BTKi) approved by the FDA for the treatment of relapsed/refractory (R/R) mantle cell lymphoma, and is in advanced stages of clinical testing for front line (FL) and R/R CLL (Byrd NEJM, Wang NEJM). Ibrutinib (ibr) is a well-established and potent treatment for CLL; however, discontinuation due to intolerance precludes a significant number of patients (pts) in clinical practice from long-term benefit of this targeted therapy (Mato et al Blood 2016, Follows BJH 2017). Acala inhibits BTK more selectively than ibr, and while demonstrating impressive activity, may result in significantly less off-target adverse events (AEs). Although not yet FDA approved, it is being increasingly used in CLL pts with ibr-intolerance or cardiovascular or hematologic comorbidities (atrial fibrillation (AF), hypercoagulable state on long-term anticoagulation, etc.) to potentially avoid ibr-related toxicities. The increasing use of acala in clinical practice provides an opportunity to address various knowledge gaps. Therefore, we conducted a multi-institutional, retrospective analysis in CLL pts treated with acala in the real-world setting. We aimed to report and analyze the main reasons for starting acala, its safety, efficacy, outcome and sequencing. Patients and Methods: This multi-institutional, retrospective analysis included acala-treated CLL pts at 9 US cancer centers. We analyzed and described prior treatments, dosing of acala, discontinuations, toxicities and outcomes. The primary endpoint was progression-free survival (PFS) as predicted by the Kaplan Meier method. Results: 69 CLL pts treated with acala (off clinical trials) were identified. Baseline characteristics are described in Table 1. Median age was 70 years (range 51-89) and 6 (9%) and 63 (91%) pts received acala in the FL and R/R settings, respectively. Of the R/R pts, 49 (78%) had received a prior BTKi, 11 (17%) a phosphoinositide 3-kinase inhibitor (PI3Ki), 14 (22%) venetoclax, 18 (29%) bendamustine, and 17 (27%) fludarabine. Median time from diagnosis of CLL to starting acala was 79.5 months. Most common reasons for choosing acala were prior intolerance to other agents in 47 (68%), disease progression on the prior line of therapy in 19 (28%) and concern for intolerance to other therapies due to age/comorbidities in 9 (13%). Prior intolerance to ibr was the reason for starting acala in 46 (98%) of the intolerant pts; the most common AEs leading to discontinuation of ibr were rash in 10 (22%), AF/flutter in 8 (17%), arthralgia in 8 (17%), bleeding in 6 (13%), infection in 6 (13%) and fatigue in 6 (13%). Almost all pts (99%) started on acala 100 mg orally twice daily, with dose reductions required in 5 (7%). The most common toxicities on acala were fatigue in 9 (13%), infection in 9 (13%), diarrhea/colitis in 7 (10%), nausea/vomiting in 6 (9%), headache in 5 (7%), rash in 5 (7%), bleeding in 2 (3%) and AF/flutter in 1 (1%). The median time from the start of acala to an infection was 3 months. With a median follow-up of 5 months, the acala discontinuation rate was estimated to be 19% (13 pts) with median time to discontinuation of 1 month. The main reason for discontinuation was AEs in 8 pts (12%) (no consistent pattern of AEs), all in R/R pts with median time to discontinuation of 3.5 months; 2 others proceeded to CAR T-cell therapy or allogeneic transplant; 2 died of unrelated causes, 1 from progressive disease off acala. Overall response rate (ORR) was 62% (9% CR, 53% PR, number reported = 66), 50% PR in FL (3/6) and 63% (CR 5%, PR 58%, number reported = 60) in R/R pts. The differences likely reflected small numbers and short follow-up. Median PFS and overall survival were not reached (Figs 1a,b). Conclusion: In this group of largely ibr-intolerant pts, the overall acala discontinuation rate was lower than prior reports from clinical trials, although with relatively short follow up. However, discontinuation rate due to AEs appears to be similar to clinical trial data in an ibr-intolerant pt population (Awan Blood Adv, Rogers ICML 2019). These data demonstrate the need for the results of randomized studies, in order to compare the efficacy and AE profile of acala relative to ibr and other novel agents and Disclosures Yazdy: Genentech: Research Funding; Bayer: Honoraria, Speakers Bureau; Octapharma: Consultancy; Abbvie: Consultancy. Mato:Genentech: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Celgene: Consultancy; Johnson & Johnson: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB member , Research Funding; Acerta: Consultancy; Janssen: Consultancy; Gilead: Research Funding; DTRM Biopharma: Research Funding; AstraZeneca: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; LOXO: Consultancy, Research Funding. Roeker:AbbVie: Equity Ownership; Abbott Laboratories: Equity Ownership. Ujjani:Gilead: Consultancy; Atara: Consultancy; Genentech: Honoraria; AbbVie: Honoraria, Research Funding; PCYC: Research Funding; Pharmacyclics: Honoraria; PCYC: Research Funding; Pharmacyclics: Honoraria; Astrazeneca: Consultancy. Shadman:TG Therapeutics: Research Funding; Gilead: Research Funding; Merck: Research Funding; Bigene: Research Funding; Celgene: Research Funding; Acerta: Research Funding; Emergent: Research Funding; Sunesis: Research Funding; Mustang Biopharma: Research Funding; Atara: Consultancy; Pharmacyclics: Consultancy, Research Funding; Verastem: Consultancy; AbbVIe: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; AstraZeneca: Consultancy; Sound Biologics: Consultancy; ADC Therapeutics: Consultancy. Skarbnik:Genentech: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Acerta: Research Funding; Novartis: Speakers Bureau; Jazz Pharmaceuticals: Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Verastem Oncology: Honoraria, Research Funding, Speakers Bureau; Kite Pharma: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; CLL Society: Consultancy, Membership on an entity's Board of Directors or advisory committees. Pagel:AstraZeneca: Consultancy; Gilead Sciences: Consultancy; Pharmacyclics: Consultancy. Patel:Sunesis: Consultancy; Pharmacyclics/Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Genentech: Consultancy, Speakers Bureau. Jacobs:AstraZeneca: Speakers Bureau; Gilead: Consultancy; Genentech: Speakers Bureau; JUNO: Consultancy; TG Therapeutics: Honoraria, Research Funding; AbbVie: Consultancy, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Research Funding, Speakers Bureau. Feldman:Portola Pharma: Research Funding; Roche: Research Funding; Corvus: Research Funding; Eisai: Research Funding; Kyowa Hakko Kirin: Research Funding; Roche: Research Funding; Trillium: Research Funding; Viracta: Research Funding; Pfizer: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Amgen: Research Funding; Cell Medica: Research Funding; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau. Goy:University of Nebraska: Research Funding; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants outside of the submitted work, Research Funding; Hakensackumc: Research Funding; Hackensack University Medical Center, RCCA: Employment; Genentech: Other: Grants outside of the submitted work, Research Funding; Pharmacyclics/Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants outside of the submitted work, Research Funding; Takeda: Other: Grants outside of the submitted work; Astrazenca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants outside of the submitted work; COTA: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: leadership role for profit healthcare company; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Coombs:Pharmacyclics: Honoraria; Loxo: Honoraria; H3 Biomedicine: Honoraria; Octopharma: Honoraria; Dedham Group: Consultancy; Cowen & Co.: Consultancy; Medscape: Honoraria; Abbvie: Consultancy; Covance: Consultancy. Lamanna:Celgene: Consultancy; Infinity/ Verastem: Research Funding; Ming: Research Funding; TG Therapeutics: Research Funding; Oncternal: Research Funding. Weiss:TG Therapeutics: Other: family member with employment and equity) . Cheson:AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; Portola: Research Funding; Kite: Research Funding; Gilead: Research Funding; Epizyme: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Symbios: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trillium: Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: Acalabrutinib is an irreversible, second generation Bruton tyrosine kinase inhibitor approved by the FDA for the treatment of relapsed/refractory (R/R) mantle cell lymphoma, and is in advanced stages of clinical development testing for front line (FL) and R/R CLL. Although not yet FDA approved, it is being increasingly used in CLL patients in clinical practice. This highlights the necessity to address various knowledge gaps.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-130062

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2629-2629

Abstract: Background: Non-covalent Bruton's Tyrosine Kinase inhibitors (ncBTKi) are in clinical development for the treatment of chronic lymphocytic leukemia (CLL) and Richter Transformation (RT). These agents (pirtobrutinib, ARQ-531, SNS-062) reversibly bind BTK and overcome acquired resistance to covalent BTKis (cBTKi). In the phase I/II trial of pirtobrutinib, clinical activity was observed in a heavily pre-treated patient (pt) population including CLL pts with acquired mutations in BTK and pts with RT. Given the efficacy of ncBTKis, these agents hold promise to address an unmet need for pts with CLL. As an increasing number of pts are treated with ncBTKis, data on the sequential use of each therapy are critical to guide clinical decision-making following their discontinuation and where ncBTKi may ultimately fit into the CLL sequencing paradigm. Currently, there are no available data on treatment of CLL or RT following discontinuation of ncBTKis. Therefore, we sought to report outcomes for CLL and RT pts following discontinuation of ncBTKis. Methods: We conducted a retrospective, multicenter, international study of pts treated with any ncBTKi for a diagnosis CLL or RT who have discontinued ncBTKi. Data was collected using a standardized data template which included pt and disease characteristics, prior therapies, demographics, response to ncBTKi and subsequent therapies and outcomes. Data on up to two lines of therapies following ncBTKi were collected. The primary study endpoint was investigator-assessed overall response rate (ORR) for therapies following ncBTKi discontinuation. Analyses were descriptive and were performed using STATA 17.0. Results: 42 pts with CLL (n=33) or RT (n=9) were identified who were treated with and subsequently discontinued a ncBTKi. Baseline characteristics at start of ncBTKi are presented in Table 1. Pts were treated with a median of 3.5 (range 1-10) prior therapies including: cBTKi (95%), chemo+/-immunotherapy (CIT, 76%), venetoclax (50%), phosphatidylinositol 3-kinase inhibitors (PI3Ki, 33%) and cellular therapies (14%). Baseline disease characteristics included unmutated IGHV (74%), del17p (49%) and TP53 mutation (45%). Best ORR to ncBTKi was 48.5% in CLL pts and 44.4% in RT pts. Median duration of treatment exposure was 5.5 months (range 1-18). The six most common reasons for discontinuation were progressive CLL 38.1%, progression of existing RT 14.3%, CLL progression to RT 9.5%, allogeneic stem cell transplant (allo SCT) 9.5%, death not secondary to progression or toxicity 7.1%, and adverse events 7.1%. Presently, 32 pts (76.2%) received another line of therapy following discontinuation of ncBTKi. Therapies and ORR following ncBTKi discontinuation are presented in Table 2. The 3 most common treatment strategies included: cellular therapy (11 pts), venetoclax-based therapy (10 pts) and CIT for RT (9 pts). ORR to any first line of therapy post ncBTKi was 46.7% (n=30 pts with response data). ORR to any second line of therapy following ncBTKi was 45.4% (n=11 pts with response data). Focusing on specific treatment strategies, ORR to cellular therapy (allo SCT or chimeric antigen receptor (CAR) T-cell therapy) for RT or CLL was 81.8% (complete response (CR): 6, partial response (PR): 3, stable disease (SD): 1, progression of disease (PD):1, n=11) with an ORR of 80.0% (n=5) after CAR T-cell therapy and an of ORR 75.0% after allo SCT (n=4). ORR to venetoclax-based therapy was 60.0% (CR: 0, PR: 6, SD: 3, PD: 1, n=10, all CLL pts, 9 venetoclax naïve pts). Additionally, two pts received alternative ncBTKis (PR: 1, SD: 1). CIT was ineffective for either RT or CLL (ORR: 12.5% and 33.3%, respectively). At the time of data cut, 15 of 42 (35.7%) pts had died with 9 deaths due to CLL or RT. Conclusion: In this first study to report outcomes of CLL and RT pts who have discontinued a ncBTKi, several important themes have emerged. For venetoclax naive CLL pts, venetoclax appears to be a promising strategy following ncBTKi discontinuation supporting the ability to stay within the BTKi class prior to switching to venetoclax. Cellular therapies including CAR T-cell therapy and allo SCT had a high ORR and warrant further investigation (80% of pts had prior cBTKi, ncBTKi and venetoclax and 100% had prior cBTKi and ncBTKi). CIT was associated with very low response rates and poor outcomes for both RT and CLL. Data to be updated with additional pts and survival outcomes. Figure 1 Figure 1. Disclosures Thompson: MJH Life Sciences: Honoraria; Curio Science: Honoraria; VJHemOnc: Honoraria. Coombs: LOXO: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria; Genentech: Honoraria; MEI Pharma: Honoraria. Roeker: Pfizer: Consultancy, Research Funding; TG Therapeutics: Consultancy; Pharmacyclics: Consultancy; Abbot Laboratories: Current equity holder in publicly-traded company; AbbVie, AstraZeneca, Janssen, LOXO, Pharmacyclics, TG Therapeutics, Vaniam Group, Verastem: Consultancy; Loxo Oncology: Consultancy. Pagel: Gilead: Consultancy; Epizyme: Consultancy; AstraZeneca: Consultancy; Pharmacyclics/AbbVie: Consultancy; MEI Pharma: Consultancy; Kite, a Gilead Company: Consultancy; Actinium Pharmaceuticals: Consultancy; Incyte/MorphoSys: Consultancy; BeiGene: Consultancy. Battiato: Janssen: Honoraria; Abbvie: Honoraria. Rhodes: Conquer Cancer Foundation Young Investigator Award: Other: Grant/Research Support; AbbVie, Genentech, Pharmacyclics, TG Therapeutics: Other: Consultant. Fakhri: Loxo/Lilly: Research Funding. Eyre: Secura Bio: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen: Honoraria; Incyte: Consultancy; AstraZeneca: Honoraria, Research Funding; Loxo Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Other: Travel to conferences; Gilead/KITE: Honoraria, Other: Travel support for conferences, Research Funding, Speakers Bureau. Mato: TG Therapeutics: Consultancy, Other: DSMB, Research Funding; Janssen: Consultancy, Research Funding; Acerta/AstraZeneca: Consultancy, Research Funding; Johnson and Johnson: Consultancy, Research Funding; DTRM BioPharma: Consultancy, Research Funding; Genmab: Research Funding; Nurix: Research Funding; MSKCC: Current Employment; AstraZeneca: Consultancy; Sunesis: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; LOXO: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-148592

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Future Oncology, Future Medicine Ltd, Vol. 18, No. 33 ( 2022-10), p. 3689-3699

Abstract: Tweetable abstract Phase III global multicenter frontline CLL trial now enrolling. MAJIC: acalabrutinib + venetoclax vs venetoclax + obinutuzumab. MRD-guided therapy duration. 600 previously untreated pts.

Type of Medium: Online Resource

ISSN: 1479-6694 , 1744-8301

URL: Article

DOI: 10.2217/fon-2022-0456

Language: English

Publisher: Future Medicine Ltd

Publication Date: 2022

In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. CT138-CT138

Abstract: Background: Covalent Bruton tyrosine kinase inhibitors (BTKi) have transformed the management of chronic lymphocytic leukemia (CLL), but patients (pts) discontinue these agents due to resistance or intolerance. Pirtobrutinib is an oral, highly selective, non-covalent (reversible) BTKi with promising efficacy and safety in heavily pretreated relapsed/refractory (R/R) CLL pts, regardless of BTK C481 mutation status. Recent clinical studies reported on the safety and efficacy of time-limited venetoclax and covalent BTKi combination regimens. We evaluated the safety and efficacy of pirtobrutinib combined with venetoclax ± rituximab in pts with R/R CLL. Methods: BRUIN is a phase 1/2 global, multicenter study (NCT03740529) of pirtobrutinib in pts with advanced B-cell malignancies. The phase 1b portion evaluated the safety of pirtobrutinib at a continuous dose of 200 mg QD from Cycle 1, Day 1 plus venetoclax starting on Cycle 2, Day 1 with a standard 5-week dose ramp to 400 mg QD (PV) and PV plus rituximab at 375 mg/m2 on Cycle 1, Day 1, then 500 mg/m2 on Day 1 of Cycles 2-6 (PVR). Prior BTKi was allowed; prior venetoclax was not permitted. Objectives included safety and overall response rate (ORR) of each combination. Results: As of 27 SEP 2021, 15 pts received PV and 10 pts received PVR. Median age was 66 years (range, 39-78). Median prior lines of therapy was 2 (range, 1-4). The majority of pts in both cohorts had received prior chemotherapy (56%, n=14), CD20 monoclonal antibody (72%, n=18), and/or covalent BTKi (68%, n=17). No dose-limiting toxicities were reported. Safety profiles were generally similar across both cohorts. The most common treatment-emergent adverse events (TEAE) of any grade, regardless of attribution, were neutrophil count decrease (36%), nausea (32%), fatigue (32%), diarrhea (28%), and constipation (24%). The only Grade ≥3 TEAE to occur in more than 2 pts was neutrophil count decrease (36%, n=9). One pt experienced Grade 4 clinical tumor lysis syndrome with resultant acute kidney injury during venetoclax dose escalation, which resolved with supportive measures. No pts discontinued treatment due to AEs. For the 22 pts with efficacy data available as of 03 NOV 2021, median duration of follow-up was 9 months (range, 3.9-15) and the ORR was 95.5% (95% CI, 77-100). All responding pts except 1 remain on therapy (PVR responder discontinued due to death unrelated to study treatment). As all responses were ongoing and early, and MRD analysis was not yet performed. Conclusions: Pirtobrutinib combined with venetoclax ± rituximab was well tolerated and had a safety profile consistent with known drug class findings and no clear additive toxicities in pts with R/R CLL. Early results demonstrate promising efficacy with combination therapy. Citation Format: Lindsey E. Roeker, Anthony R. Mato, Jennifer R. Brown, Catherine C. Coombs, Nirav N. Shah, William G. Wierda, Manish R. Patel, Katharine L. Lewis, Minna Balbas, Junjie Zhao, Nora C. Ku, Jennifer F. Kherani, Donald E. Tsai, Binoj Nair, Chan Y. Cheah. Pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in combination with venetoclax ± rituximab in relapsed/refractory chronic lymphocytic leukemia: Results from the BRUIN phase 1b study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT138.

Type of Medium: Online Resource

ISSN: 1538-7445

URL: Article

DOI: 10.1158/1538-7445.AM2022-CT138

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2022

detail.hit.zdb_id: 2036785-5

detail.hit.zdb_id: 1432-1

detail.hit.zdb_id: 410466-3

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 846-849

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-157058

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2628-2628

Abstract: Background: Targeted therapies including ibrutinib, acalabrutinib and venetoclax (ven) have fundamentally changed the treatment of patients (pts) with chronic lymphocytic leukemia (CLL) leading to improved outcomes and durable remissions for many pts. However, CLL remains an incurable disease and a subset of pts will ultimately have progressive CLL following treatment with a covalent Bruton's Tyrosine Kinase inhibitor (cBTKi, e.g., ibrutinib, acalabrutinib) and ven. Data on efficacy of therapies for "double exposed" pts (i.e., pts exposed to both a cBTKi and ven) are extremely limited. Available approved options include chemoimmunotherapy (CIT) and phosphatidylinositol 3-kinase inhibitors (PI3Ki). However, the landmark clinical trials leading to the approvals of CIT and PI3Kis did not include pts treated with either cBTKi or ven (Furman et al. NEJM 2014, Flinn et al. Blood 2018). Non-covalent BTKis (ncBTKi) and chimeric antigen receptor (CAR) T-cell therapy have demonstrated promising clinical activity in double exposed CLL pts in clinical trials (Mato et al. Lancet 2021, Siddiqi et al. ASH 2020), but have not yet been compared to other novel agents or CIT in clinical trials or real-world analyses. We sought to describe outcomes of therapies for "double exposed" CLL pts. Methods: A retrospective, international, multicenter study was conducted. CLL pts were included if they received a cBTKi and ven and then a subsequent CLL-directed therapy. Therapies for Richter Transformation were excluded. Investigators identified pts at each site and collected data on demographics, disease characteristics, prior therapies, subsequent therapies and response assessments. Information was collected on up to three subsequent lines of therapy (LOT 1-3) per patient. The primary study endpoint was investigator-assessed overall response rate (ORR) per iwCLL 2018 criteria to therapies (LOT 1-3) following both cBTKi and ven. Kaplan-Meier method was used to estimate progression free survival (PFS). All other analyses were descriptive. Analyses were performed using STATA 17.0. Results: We report outcomes on 125 CLL pts who had prior cBTKi and ven and received a subsequent LOT. Baseline characteristics are presented in Table 1. ORR to prior cBTKi was 84.7% and 69.6% to prior ven. The most common reason for discontinuation of prior cBTKi and ven was CLL progression (71.1% cBTKi, 68.8% ven) followed by toxicity (25.6% cBTKi, 16.8% ven). Most common treatment strategies included ncBTKi (n=45), cBTKi (n=43), CIT (n=23), PI3Ki (n=24), alloSCT (n=17), CAR T-cell therapy (n=9), ven re-treatment (n=6), and other (n=44). ORR for selected agents following cBTKi and ven are presented in Table 2. ORR and PFS estimates were as follows: CAR T-cell therapy (85.7%, median PFS 4 months), alloSCT (76.5%, median PFS 11 months), ncBTKi (75.0%, median PFS not reached), PI3Ki (40.9%, median PFS 5 months), CIT (31.8%, median PFS 3 months) and ven re-treatment (ORR 40%, median PFS 14 months). ORR to cBTKi was 53.7%; however, median PFS for pts who discontinued a previous cBTKi for PD was 1 month versus 7 months for pts who discontinued due to AE. Figure 1 shows Kaplan-Meier estimated PFS for ncBTKi, PI3Ki, alloSCT, and CIT. Conclusions: In the largest series of "double exposed" CLL pts, several key findings warrant further investigation and discussion. Practice patterns are variable and no standard of care exists for CLL pts previously treated with a cBTKi and ven. Additionally, approved standard therapies including CIT combinations and PI3Kis yield poor outcomes with responses which are not durable. The low response rates and short PFS for PI3Ki and CIT call into question the use of these therapies as standard comparator arms in planned randomized trials. At this time, ncBTKi has a high ORR with durable responses (median PFS not reached). There appears to be a promising role for alloSCT in select, fit patients (ORR 76.5%, median PFS 11 months), and CAR T-cell therapy should be further explored in this population (ORR 85.7%, median PFS 4 months). Overall, this study highlights a continued unmet need for therapies for "double exposed" CLL pts. Figure 1 Figure 1. Disclosures Thompson: MJH Life Sciences: Honoraria; VJHemOnc: Honoraria; Curio Science: Honoraria. Roeker: Abbot Laboratories: Current equity holder in publicly-traded company; Pharmacyclics: Consultancy; Loxo Oncology: Consultancy; TG Therapeutics: Consultancy; AbbVie, AstraZeneca, Janssen, LOXO, Pharmacyclics, TG Therapeutics, Vaniam Group, Verastem: Consultancy; Pfizer: Consultancy, Research Funding. Coombs: LOXO: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria; Genentech: Honoraria; MEI Pharma: Honoraria. Kamdar: AbbVie: Consultancy; TG Therapeutics: Research Funding; SeaGen: Speakers Bureau; ADC Therapeutics: Consultancy; Adaptive Biotechnologies: Consultancy; AstraZeneca: Consultancy; Celgene: Other; Celgene (BMS): Consultancy; Kite: Consultancy; KaryoPharm: Consultancy; Genentech: Research Funding; Genetech: Other. Pagel: Epizyme: Consultancy; Incyte/MorphoSys: Consultancy; BeiGene: Consultancy; Pharmacyclics/AbbVie: Consultancy; Actinium Pharmaceuticals: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy; Kite, a Gilead Company: Consultancy; MEI Pharma: Consultancy. Jacobs: MEI Pharma: Research Funding; Adaptive Biotechnologies: Consultancy; Genentech: Consultancy; TG Therapeutics: Research Funding, Speakers Bureau; Verastem: Consultancy; AstraZeneca: Consultancy, Speakers Bureau; ADC Therapeutics: Consultancy; TeneoBio: Research Funding; AbbVie: Consultancy, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; Jannsen: Speakers Bureau; SecuraBio: Consultancy, Speakers Bureau. Hill: Gentenech: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Incyte/Morphysis: Consultancy, Honoraria, Research Funding; Celgene (BMS): Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Brander: AbbVie: Consultancy, Other: informCLL registry steering committee, Research Funding; AstraZeneca: Research Funding; BeiGene: Research Funding; ArQule: Research Funding; DTRM: Research Funding; LOXO: Research Funding; Verastem: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Juno Therapeutics/Celgene/Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Ascentage: Research Funding; MEI Pharma: Research Funding; Genentech: Consultancy, Research Funding; NCCN: Other: panel member; Pfizer: Consultancy, Other: Biosimilars outcomes research panel; ArQule/Merck: Consultancy. Shadman: Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding; Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune , Mustang Bio and Atara Biotherapeutics: Consultancy. Ujjani: AbbVie: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Research Funding; Adaptive Biotechnologies: Research Funding; Atara Bio: Consultancy; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; TG Therapeutics: Honoraria; Gilead: Honoraria; ACDT: Honoraria; Kite, a Gilead Company: Honoraria. Battiato: Abbvie: Honoraria; Janssen: Honoraria. Rhodes: AbbVie, Genentech, Pharmacyclics, TG Therapeutics: Other: Consultant; Conquer Cancer Foundation Young Investigator Award: Other: Grant/Research Support. Fakhri: Loxo/Lilly: Research Funding. Barr: Morphosys: Consultancy; Gilead: Consultancy; Seattle Genetics: Consultancy; TG Therapeutics: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy; Beigene: Consultancy; Bristol Meyers Squibb: Consultancy; Abbvie/Pharmacyclics: Consultancy; Genentech: Consultancy. Portell: TG Therapeutics: Honoraria, Research Funding; SeaGen: Research Funding; Kite: Honoraria, Research Funding; Xencor: Research Funding; Abbvie: Research Funding; Pharmacyclics: Honoraria; Merck: Honoraria, Research Funding; BeiGene: Honoraria, Research Funding; Acerta/AstraZeneca: Research Funding; Aptitude Health: Honoraria; Targeted Oncology: Honoraria; Morphosys: Honoraria; Genentech: Research Funding; VelosBio: Research Funding. Lamanna: AbbVie: Consultancy, Research Funding; Verastem Oncology: Research Funding; BeiGene: Consultancy; Pharmacyclics: Consultancy; Celgene Corporation: Consultancy; Oncternal Therapeutics: Research Funding; Janssen Pharmaceuticals, Inc.: Consultancy; Gilead Sciences, Inc.: Consultancy; MingSight Pharmaceuticals, Inc.: Research Funding; Genentech, Inc.: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; TG Therapeutics, Inc: Research Funding; Juno Therapeutics, Inc.: Research Funding. Zelenetz: MorphoSys: Honoraria; Verastem: Honoraria; LFR: Other; Gilead: Honoraria, Research Funding; NCCN: Other; AstraZeneca: Honoraria; MEI Pharma: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Janssen: Honoraria; Gilead: Honoraria; Pharmacyclics: Honoraria; BMS/Celgene/JUNO: Honoraria, Other; Novartis: Honoraria; SecuraBio: Honoraria; Genentech/Roche: Honoraria, Research Funding; MethylGene: Research Funding; Amgen: Honoraria; Beigene: Honoraria, Other, Research Funding. Schuster: Abbvie: Consultancy, Research Funding; Acerta Pharma: Consultancy; AstraZeneca: Consultancy; Adaptive Biotechnologies: Research Funding; BeiGene: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; DTRM: Research Funding; Genetech: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Incyte: Research Funding; Juno Theraputics: Consultancy, Research Funding; Loxo Oncology: Consultancy; Merck: Research Funding; Nordic Nanovector: Consultancy; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; Pharmaclcyclics: Research Funding; Tessa Theraputics: Consultancy; TG Theraputics: Research Funding. Eyre: Secura Bio: Consultancy, Honoraria; Loxo Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Research Funding; Incyte: Consultancy; Beigene: Honoraria, Research Funding; Roche: Consultancy, Honoraria; Gilead/KITE: Honoraria, Other: Travel support for conferences, Research Funding, Speakers Bureau; Janssen: Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel to conferences. Mato: MSKCC: Current Employment; AstraZeneca: Consultancy; Genmab: Research Funding; LOXO: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Johnson and Johnson: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; DTRM BioPharma: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Acerta/AstraZeneca: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Nurix: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-150751

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: The Lancet, Elsevier BV, Vol. 397, No. 10277 ( 2021-03), p. 892-901

Type of Medium: Online Resource

ISSN: 0140-6736

URL: Article

DOI: 10.1016/S0140-6736(21)00224-5

Language: English

Publisher: Elsevier BV

Publication Date: 2021

detail.hit.zdb_id: 2067452-1

detail.hit.zdb_id: 3306-6

detail.hit.zdb_id: 1476593-7

SSG: 5,21