Real-world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in he United States

被引：146

作者：

Mato, Anthony R. ^{[1
]}

Thompson, Meghan ^{[2
]}

Allan, John N. ^{[3
]}

Brander, Danielle M. ^{[4
]}

Pagel, John M. ^{[5
]}

Ujjani, Chaitra S. ^{[6
]}

Hill, Brian T. ^{[7
]}

Lamanna, Nicole ^{[8
]}

Lansigan, Frederick ^{[9
]}

Jacobs, Ryan ^{[10
]}

Shadman, Mazyar ^{[11
]}

Skarbnik, Alan P. ^{[12
]}

Pu, Jeffrey J. ^{[13
]}

Barr, Paul M. ^{[14
]}

Sehgal, Alison R. ^{[15
]}

Cheson, Bruce D. ^{[6
]}

Zent, Clive S. ^{[14
]}

Tuncer, Hande H. ^{[16
]}

Schuster, Stephen J. ^{[2
]}

Pickens, Peter V. ^{[17
]}

Shah, Nirav N. ^{[18
]}

Goy, Andre ^{[12
]}

Winter, Allison M. ^{[7
]}

Garcia, Christine ^{[15
]}

Kennard, Kaitlin ^{[2
]}

Isaac, Krista ^{[19
]}

Dorsey, Colleen ^{[2
]}

Gashonia, Lisa M. ^{[2
]}

Singavi, Arun K. ^{[18
]}

Roeker, Lindsey E. ^{[1
]}

Zelenetz, Andrew ^{[1
]}

Williams, Annalynn ^{[14
]}

Howlett, Christina ^{[12
]}

Weissbrot, Hanna ^{[8
]}

Ali, Naveed ^{[17
]}

Khajavian, Sirin ^{[11
]}

Sitlinger, Andrea ^{[4
]}

Tranchito, Eve ^{[7
]}

Rhodes, Joanna ^{[2
]}

Felsenfeld, Joshua ^{[3
]}

Bailey, Neil ^{[5
]}

Patel, Bhavisha ^{[20
]}

Burns, Timothy F. ^{[9
]}

Yacur, Melissa ^{[13
]}

Malhotra, Mansi ^{[16
]}

Svoboda, Jakub ^{[2
]}

Furman, Richard R. ^{[3
]}

Nabhan, Chadi ^{[21
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Internal Med, Div Hematol Oncol, CLL Program,Leukemia Serv, 1275 York Ave, New York, NY 10021 USA

[2] Univ Penn, Div Hematol & Oncol, Ctr CLL, Philadelphia, PA 19104 USA

[3] New York Presbyterian & Weill Cornell, New York, NY USA

[4] Duke Univ, Div Hematol Malignancies & Cellular Therapy, Durham, NC USA

[5] Swedish Canc Inst, Ctr Blood Disorders & Stem Cell Transplantat, Seattle, WA USA

[6] Georgetown Univ Hosp, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA

[7] Cleveland Clin Fdn, Taussig Canc Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA

[8] Columbia Univ, Med Ctr, New York, NY USA

[9] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA

[10] Carolinas Healthcare Syst, Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA

[11] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98195 USA

[12] Hackensack Meridian Hlth, John Theurer Canc Ctr, Hackensack, NJ USA

[13] Penn State Hlth, Hershey, PA USA

[14] Univ Rochester, Med Ctr, Div Hematol Oncol, Wilmot Inst, Rochester, NY 14627 USA

[15] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA

[16] Tufts Med Ctr, Boston, MA USA

[17] Abington Hem Onc Assoc Inc, Willow Grove, PA USA

[18] Med Coll Wisconsin, Div Hematol & Oncol, Brookfield, WI USA

[19] Lankenau Med Ctr, Internal Med, Wynnewood, PA USA

[20] Washington Hosp Ctr, Washington, DC 20010 USA

[21] Cardinal Hlth, Dublin, OH USA

来源：

HAEMATOLOGICA | 2018年 / 103卷 / 09期

关键词：

IBRUTINIB; MULTICENTER; BCL2; CLL;

D O I：

10.3324/haematol.2018.193615

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Venetoclax is a BCL2 inhibitor approved for 17 deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with chronic lymphocytic leukemia treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV, 45% del(17p), and 26.8% complex karyotype (>= 3 abnormalities). Prior to venetoclax initiation, 89% received a B-cell receptor antagonist. For tumor lysis syndrome prophylaxis, 93% received allopurinol, 92% normal saline, and 45% rasburicase. Dose escalation to the maximum recommended dose of 400 mg daily was achieved in 85% of patients. Adverse events of interest included neutropenia in 47.4%, thrombocytopenia in 36%, tumor lysis syndrome in 13.4%, neutropenic fever in 11.6%, and diarrhea in 7.3%. The overall response rate to venetoclax was 72% (19.4% complete remission). With a median follow up of 7 months, median progression free survival and overall survival for the entire cohort have not been reached. To date, 41 venetoclax treated patients have discontinued therapy and 24 have received a subsequent therapy, most commonly ibrutinib. In the largest clinical experience of venetoclax-treated chronic lymphocytic leukemia patients, the majority successfully completed and maintained a maximum recommended dose. Response rates and duration of response appear comparable to clinical trial data. Venetoclax was active in patients with mutations known to confer ibrutinib resistance. Optimal sequencing of newer chronic lymphocytic leukemia therapies requires further study.

引用

页码：1511 / 1517

页数：7

共 20 条

[1] COX REGRESSION-MODEL FOR COUNTING-PROCESSES - A LARGE SAMPLE STUDY [J].

ANDERSEN, PK ;

GILL, RD .

ANNALS OF STATISTICS, 1982, 10 (04) :1100-1120

[2] Clinicopathological features and outcomes of progression of CLL on the BCL2 inhibitor venetoclax [J].

Anderson, Mary Ann ;

Tam, Constantine ;

Lew, Thomas E. ;

Juneja, Surender ;

Juneja, Manu ;

Westerman, David ;

Wall, Meaghan ;

Lade, Stephen ;

Gorelik, Alexandra ;

Huang, David C. S. ;

Seymour, John F. ;

Roberts, Andrew W. .

BLOOD, 2017, 129 (25) :3362-3370

[3]

[Anonymous], HEMATOL ONCOL

[4] Statistics notes - Survival probabilities (the Kaplan-Meier method) [J].

Bland, JM ;

Altman, DG .

BRITISH MEDICAL JOURNAL, 1998, 317 (7172) :1572-1572

[5] The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia [J].

Brown, Jennifer R. ;

Barrientos, Jacqueline C. ;

Barr, Paul M. ;

Flinn, Ian W. ;

Burger, Jan A. ;

Anh Tran ;

Clow, Fong ;

James, Danelle F. ;

Graef, Thorsten ;

Friedberg, Jonathan W. ;

Rai, Kanti ;

O'Brien, Susan .

BLOOD, 2015, 125 (19) :2915-2922

[6] Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy [J].

Coutre, Steven ;

Choi, Michael ;

Furman, Richard R. ;

Eradat, Herbert ;

Heffner, Leonard ;

Jones, Jeffrey A. ;

Chyla, Brenda ;

Zhou, Lang ;

Agarwal, Suresh ;

Waskiewicz, Tina ;

Verdugo, Maria ;

Humerickhouse, Rod A. ;

Potluri, Jalaja ;

Wierda, William G. ;

Davids, Matthew S. .

BLOOD, 2018, 131 (15) :1704-1711

[7]

Davids MS, 2017, BLOOD, V130

[8]

FDA, 2018, HIGHL PRESCR INF VEN

[9]

Hallek M, 2008, GUIDELINES, V111, P5445

[10] The Tumor Lysis Syndrome [J].

Howard, Scott C. ;

Jones, Deborah P. ;

Pui, Ching-Hon .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (19) :1844-1854

← 1 2 →