Annals of Hematology

, Volume 95, Issue 4, pp 563–573 | Cite as

Tumor lysis syndrome in the era of novel and targeted agents in patients with hematologic malignancies: a systematic review

  • Scott C. HowardEmail author
  • Steven Trifilio
  • Tara K. Gregory
  • Nadine Baxter
  • Ali McBride
Original Article


Effective new treatments are now available for patients with hematologic malignancies. However, their propensity to cause tumor lysis syndrome (TLS) has not been systematically examined. A literature search identified published Phase I–III clinical trials of monoclonal antibodies (otlertuzumab, brentuximab, obinutuzumab, ibritumomab, ofatumumab); tyrosine kinase inhibitors (alvocidib [flavopiridol], dinaciclib, ibrutinib, nilotinib, dasatinib, idelalisib, venetoclax [ABT-199]); proteasome inhibitors (oprozomib, carfilzomib); chimeric antigen receptor (CAR) T cells; and the proapoptotic agent lenalidomide. Abstracts from major congresses were also reviewed. Idelalisib and ofatumumab had no reported TLS. TLS incidence was ≤5 % with brentuximab vedotin (for anaplastic large-cell lymphoma), carfilzomib and lenalidomide (for multiple myeloma), dasatinib (for acute lymphoblastic leukemia), and oprozomib (for various hematologic malignancies). TLS incidences were 8.3 and 8.9 % in two trials of venetoclax (for chronic lymphocytic leukemia [CLL]) and 10 % in trials of CAR T cells (for B-cell malignancies) and obinutuzumab (for non-Hodgkin lymphoma). TLS rates of 15 % with dinaciclib and 42 and 53 % with alvocidib (with sequential cytarabine and mitoxantrone) were seen in trials of acute leukemias. TLS mitigation was employed routinely in clinical trials of alvocidib and lenalidomide. However, TLS mitigation strategies were not mentioned or stated only in general terms for many studies of other agents. The risk of TLS persists in the current era of novel and targeted therapy for hematologic malignancies and was seen to some extent with most agents. Our findings underscore the importance of continued awareness, risk assessment, and prevention to reduce this serious potential complication of effective anticancer therapy.


Tumor lysis syndrome Hematologic malignancies Prophylaxis Targeted treatment 



Editorial and medical writing support was provided by Laurie Orloski, PharmD, and Mariana Ovnic, PhD, at Complete Publication Solutions, LLC. This support was provided by Sanofi.


This work was supported by Sanofi.

Compliance with ethical standards

Conflict of Interest

SH has served as a consultant and/or speaker for Sanofi, Jazz Pharmaceuticals, and Sigma Tau and received research funding from Jazz Pharmaceuticals and BTG. ST has served as an advisor to Sanofi. TKG has served as a consultant to Novartis, Celgene, and Sanofi. NB has served as an advisor and speaker for Sanofi. AM has served as an advisor for Sanofi.

Supplementary material

277_2015_2585_MOESM1_ESM.docx (42 kb)
ESM 1 (DOCX 42 kb)


  1. 1.
    Bose P, Qubaiah O (2011) A review of tumour lysis syndrome with targeted therapies and the role of rasburicase. J Clin Pharm Ther 36(3):299–329. doi: 10.1111/j.1365-2710.2011.01260.x CrossRefPubMedGoogle Scholar
  2. 2.
    Howard SC, Jones DP, Pui CH (2011) The tumor lysis syndrome. N Engl J Med 364(19):1844–1854. doi: 10.1056/NEJMra0904569 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Wilson FP, Berns JS (2014) Tumor lysis syndrome: new challenges and recent advances. Adv Chronic Kidney Dis 21(1):18–26. doi: 10.1053/j.ackd.2013.07.001 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Cairo MS, Coiffier B, Reiter A, Younes A, TLS Expert Panel (2010) Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol 149(4):578–586. doi: 10.1111/j.1365-2141.2010.08143.x CrossRefPubMedGoogle Scholar
  5. 5.
    Mughal TI, Ejaz AA, Foringer JR, Coiffier B (2010) An integrated clinical approach for the identification, prevention, and treatment of tumor lysis syndrome. Cancer Treat Rev 36(2):164–176. doi: 10.1016/j.ctrv.2009.11.001 CrossRefPubMedGoogle Scholar
  6. 6.
    Karp JE, Blackford A, Smith BD, Alino K, Seung AH, Bolanos-Meade J, Greer JM, Carraway HE, Gore SD, Jones RJ, Levis MJ, McDevitt MA, Doyle LA, Wright JJ (2010) Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia. Leuk Res 34(7):877–882. doi: 10.1016/j.leukres.2009.11.007 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Seymour JF, Davids MS, Pagel JM, Kahl BS, Wierda WG, Miller TP, Gerecitano JF, Kipps TJ, Anderson MA, Huang DCS, Darden DE, Gressick LA, Nolan CE, Yang J, Busman TA, Graham AM, Cerri E, Enschede SH, Humerickhouse RA, Roberts AW (2013) Updated results of a phase I first-in-human study of the BCL-2 inhibitor ABT-199 (GDC-0199) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) [abstract]. J Clin Oncol 31(15):7018Google Scholar
  8. 8.
    Seymour JF, Davids MS, Pagel JM, Kahl BS, Wierda WG, Puvvada S, Gerecitano JF, Kipps TJ, Anderson MA, Huang DCS, Rudersdorf N, Gressick LA, Montalvo NP, Yang J, Zhu M, Dunbar M, Cerri E, Enschede SH, Humerickhouse R, Roberts AW (2014) ABT-199 (GDC-0199) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL): High complete-response rate and durable disease control. J Clin Oncol 32(15)Google Scholar
  9. 9.
    Ma S, Seymour JF, Lanasa MC, Kipps TJ, Barrientos JC, Davids MS, Mason-Bright T, Rudersdorf N, Yang J, Munasinghe W, Zhu M, Cerri E, Enschede SH, Humerickhouse R, Roberts AW (2014) ABT-199 (GDC-0199) combined with rituximab (R) in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): interim results of a phase 1b study [abstract]. J Clin Oncol 32(15):7013Google Scholar
  10. 10.
    Lin TS, Blum KA, Fischer DB, Mitchell SM, Ruppert AS, Porcu P, Kraut EH, Baiocchi RA, Moran ME, Johnson AJ, Schaaf LJ, Grever MR, Byrd JC (2010) Flavopiridol, fludarabine, and rituximab in mantle cell lymphoma and indolent B-cell lymphoproliferative disorders. J Clin Oncol 28(3):418–423. doi: 10.1200/JCO.2009.24.1570 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Blum W, Phelps MA, Klisovic RB, Rozewski DM, Ni W, Albanese KA, Rovin B, Kefauver C, Devine SM, Lucas DM, Johnson A, Schaaf LJ, Byrd JC, Marcucci G, Grever MR (2010) Phase I clinical and pharmacokinetic study of a novel schedule of flavopiridol in relapsed or refractory acute leukemias. Haematologica 95(7):1098–1105. doi: 10.3324/haematol.2009.017103 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Stephens DM, Ruppert AS, Maddocks K, Andritsos L, Baiocchi R, Jones J, Johnson AJ, Smith LL, Zhao Y, Ling Y, Li J, Phelps MA, Grever MR, Byrd JC, Flynn JM (2013) Cyclophosphamide, alvocidib (flavopiridol), and rituximab, a novel feasible chemoimmunotherapy regimen for patients with high-risk chronic lymphocytic leukemia. Leuk Res 37(10):1195–1199. doi: 10.1016/j.leukres.2013.06.006 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Holkova B, Perkins EB, Ramakrishnan V, Tombes MB, Shrader E, Talreja N, Wellons MD, Hogan KT, Roodman GD, Coppola D, Kang L, Dawson J, Stuart RK, Peer C, Figg WD Sr, Kolla S, Doyle A, Wright J, Sullivan DM, Roberts JD, Grant S (2011) Phase I trial of bortezomib (PS-341; NSC 681239) and alvocidib (flavopiridol; NSC 649890) in patients with recurrent or refractory B-cell neoplasms. Clin Cancer Res 17(10):3388–3397. doi: 10.1158/1078-0432.CCR-10-2876 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Holkova B, Supko JG, Ames MM, Reid JM, Shapiro GI, Perkins EB, Ramakrishnan V, Tombes MB, Honeycutt C, McGovern RM, Kmieciak M, Shrader E, Wellons MD, Sankala H, Doyle A, Wright J, Roberts JD, Grant S (2013) A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Clin Cancer Res 19(7):1873–1883. doi: 10.1158/1078-0432.CCR-12-2926 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Karp JE, Smith BD, Levis MJ, Gore SD, Greer J, Hattenburg C, Briel J, Jones RJ, Wright JJ, Colevas AD (2007) Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemia. Clin Cancer Res 13(15 Pt 1):4467–4473. doi: 10.1158/1078-0432.CCR-07-0381 CrossRefPubMedGoogle Scholar
  16. 16.
    Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, Yang Y, Sievers EL, Kennedy DA, Shustov A (2012) Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol 30(18):2190–2196. doi: 10.1200/JCO.2011.38.0402 CrossRefPubMedGoogle Scholar
  17. 17.
    Kochenderfer JN, Dudley ME, Carpenter RO, Kassim SH, Rose JJ, Telford WG, Hakim FT, Halverson DC, Fowler DH, Hardy NM, Mato AR, Hickstein DD, Gea-Banacloche JC, Pavletic SZ, Sportes C, Maric I, Feldman SA, Hansen BG, Wilder JS, Blacklock-Schuver B, Jena B, Bishop MR, Gress RE, Rosenberg SA (2013) Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood 122(25):4129–4139. doi: 10.1182/blood-2013-08-519413 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Jagannath S, Vij R, Stewart AK, Trudel S, Jakubowiak AJ, Reiman T, Somlo G, Bahlis N, Lonial S, Kunkel LA, Wong A, Orlowski RZ, Siegel DS (2012) An open-label single-arm pilot phase II study (PX-171-003-A0) of low-dose, single-agent carfilzomib in patients with relapsed and refractory multiple myeloma. Clin Lymphoma Myeloma Leuk 12(5):310–318. doi: 10.1016/j.clml.2012.08.003 CrossRefPubMedGoogle Scholar
  19. 19.
    Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S, Trudel S, Kukreti V, Bahlis N, Alsina M, Chanan-Khan A, Buadi F, Reu FJ, Somlo G, Zonder J, Song K, Stewart AK, Stadtmauer E, Kunkel L, Wear S, Wong AF, Orlowski RZ, Jagannath S (2012) A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood 120(14):2817–2825. doi: 10.1182/blood-2012-05-425934 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Siegel D, Martin T, Nooka A, Harvey RD, Vij R, Niesvizky R, Badros AZ, Jagannath S, McCulloch L, Rajangam K, Lonial S (2013) Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies. Haematologica 98(11):1753–1761. doi: 10.3324/haematol.2013.089334 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Berenson JR, Hilger JD, Yellin O, Dichmann R, Patel-Donnelly D, Boccia RV, Bessudo A, Stampleman L, Gravenor D, Eshaghian S, Nassir Y, Swift RA, Vescio RA (2014) Replacement of bortezomib with carfilzomib for multiple myeloma patients progressing from bortezomib combination therapy. Leukemia 28(7):1529–1536. doi: 10.1038/leu.2014.27 CrossRefPubMedGoogle Scholar
  22. 22.
    Guilhot F, Kantarjian H, Shah NP, Hochhaus A, Brigid Bradley-Garelik M, Dejardin D, Cortes JE (2010) Dasatinib (versus imatinib) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): analysis of safety and efficacy by use of baseline medications in the DASISION trial [abstract]. Blood 116(21):2295Google Scholar
  23. 23.
    Rousselot P, Cayuela JM, Hayette S, Recher C, Leguay T, Salanoubat C, Witz F, Alexis M, Hunault M, Janvier M, Agape P, Berthou C, Jourdan E, Fernandes J, Sutton L, Banos A, Reman O, Lioure B, Thomas X, Ifrah N, Gokbuget N, Hoelzer D, Delannoy A, Bassan R, Ribera JM, Giebel S, Dombret H, Ottmann OG (2010) Dasatinib (Sprycel) and low intensity chemotherapy for first-line treatment in elderly patients with de novo Philadelphia positive ALL (EWALL-PH-01): kinetic of response, resistance and prognostic significance [abstract]. Blood 116(21):172Google Scholar
  24. 24.
    Gojo I, Sadowska M, Walker A, Feldman EJ, Iyer SP, Baer MR, Sausville EA, Lapidus RG, Zhang D, Zhu Y, Jou YM, Poon J, Small K, Bannerji R (2013) Clinical and laboratory studies of the novel cyclin-dependent kinase inhibitor dinaciclib (SCH 727965) in acute leukemias. Cancer Chemother Pharmacol 72(4):897–908. doi: 10.1007/s00280-013-2249-z CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Flynn JM, Jones JA, Andritsos L, Blum KA, Johnson AJ, Hessler J, Wiley E, Poon J, Small K, Statkevich P, Grever MR, Bannerji R, Byrd JC (2010) Update on the phase I study of the cyclin dependent kinase inhibitor dinaciclib (SCH 727965) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL): confirmation of clinical activity and feasibility of long-term administration [abstract]. Blood 116(21):1396Google Scholar
  26. 26.
    Farooqui M, Aue G, Valdez J, Saba N, Herman SEM, Lipsky A, Bojanowski L, Wells A, Soto S, Liu D, Wiestner A (2012) Rapid decrease in overall tumor burden on ibrutinib (PCI-32765) in CLL despite transient increase in ALC indicates a significant degree of treatment induced cell death [abstract]. Blood 120(21):2899Google Scholar
  27. 27.
    O’Brien SM, Barrientos JC, Flinn IW, Barr PM, Burger JA, Navarro T, James DF, Hedrick E, Friedberg JW, Brown JR (2012) Combination of the Bruton’s tyrosine kinase (BTK) inhibitor PCI-32765 with bendamustine (B)/rituximab (R) (BR) in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): interim results of a phase Ib/II study [abstract]. J Clin Oncol 30(15):6515Google Scholar
  28. 28.
    Kahl BS, Spurgeon SE, Furman RR, Flinn IW, Coutre SE, Brown JR, Benson DM, Byrd JC, Peterman S, Cho Y, Yu A, Godfrey WR, Wagner-Johnston ND (2014) A phase 1 study of the PI3Kdelta inhibitor idelalisib in patients with relapsed/refractory mantle cell lymphoma (MCL). Blood 123(22):3398–3405. doi: 10.1182/blood-2013-11-537555 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Flinn IW, Kahl BS, Leonard JP, Furman RR, Brown JR, Byrd JC, Wagner-Johnston ND, Coutre SE, Benson DM, Peterman S, Cho Y, Webb HK, Johnson DM, Yu AS, Ulrich RG, Godfrey WR, Miller LL, Spurgeon SE (2014) Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-delta, as therapy for previously treated indolent non-Hodgkin lymphoma. Blood 123(22):3406–3413. doi: 10.1182/blood-2013-11-538546 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Brown JR, Byrd JC, Coutre SE, Benson DM, Flinn IW, Wagner-Johnston ND, Spurgeon SE, Kahl BS, Bello C, Webb HK, Johnson DM, Peterman S, Li D, Jahn TM, Lannutti BJ, Ulrich RG, Yu AS, Miller LL, Furman RR (2014) Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110delta, for relapsed/refractory chronic lymphocytic leukemia. Blood 123(22):3390–3397. doi: 10.1182/blood-2013-11-535047 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Witzig TE, Wiernik PH, Moore T, Reeder C, Cole C, Justice G, Kaplan H, Voralia M, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Vose JM (2009) Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin’s Lymphoma. J Clin Oncol 27(32):5404–5409. doi: 10.1200/JCO.2008.21.1169 CrossRefPubMedGoogle Scholar
  32. 32.
    Fehniger TA, Larson S, Trinkaus K, Siegel MJ, Cashen AF, Blum KA, Fenske TS, Hurd DD, Goy A, Schneider SE, Keppel CR, Wagner-Johnston ND, Carson KR, Bartlett NL (2011) A phase 2 multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma. Blood 118(19):5119–5125. doi: 10.1182/blood-2011-07-362475 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Chen CI, Bergsagel PL, Paul H, Xu W, Lau A, Dave N, Kukreti V, Wei E, Leung-Hagesteijn C, Li ZH, Brandwein J, Pantoja M, Johnston J, Gibson S, Hernandez T, Spaner D, Trudel S (2011) Single-agent lenalidomide in the treatment of previously untreated chronic lymphocytic leukemia. J Clin Oncol 29(9):1175–1181. doi: 10.1200/JCO.2010.29.8133 CrossRefPubMedGoogle Scholar
  34. 34.
    Badoux XC, Keating MJ, Wen S, Lee BN, Sivina M, Reuben J, Wierda WG, O’Brien SM, Faderl S, Kornblau SM, Burger JA, Ferrajoli A (2011) Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia. Blood 118(13):3489–3498. doi: 10.1182/blood-2011-03-339077 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Wendtner CM, Hillmen P, Mahadevan D, Buhler A, Uharek L, Coutre S, Frankfurt O, Bloor A, Bosch F, Furman RR, Kimby E, Gribben JG, Gobbi M, Dreisbach L, Hurd DD, Sekeres MA, Ferrajoli A, Shah S, Zhang J, Moutouh-de Parseval L, Hallek M, Heerema NA, Stilgenbauer S, Chanan-Khan AA (2012) Final results of a multicenter phase 1 study of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia. Leuk Lymphoma 53(3):417–423. doi: 10.3109/10428194.2011.618232 CrossRefPubMedGoogle Scholar
  36. 36.
    Badoux XC, Keating MJ, Wen S, Wierda WG, O’Brien SM, Faderl S, Sargent R, Burger JA, Ferrajoli A (2013) Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol 31(5):584–591. doi: 10.1200/JCO.2012.42.8623 CrossRefPubMedGoogle Scholar
  37. 37.
    Goy A, Sinha R, Williams ME, Kalayoglu Besisik S, Drach J, Ramchandren R, Zhang L, Cicero S, Fu T, Witzig TE (2013) Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. J Clin Oncol 31(29):3688–3695. doi: 10.1200/JCO.2013.49.2835 CrossRefPubMedGoogle Scholar
  38. 38.
    Morschhauser F, Fitoussi O, Haioun C, Thieblemont C, Quach H, Delarue R, Glaisner S, Gabarre J, Bosly A, Lister J, Li J, Coiffier B (2013) A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: the EXPECT trial. Eur J Cancer 49(13):2869–2876. doi: 10.1016/j.ejca.2013.04.029 CrossRefPubMedGoogle Scholar
  39. 39.
    Morschhauser F, Cartron G, Thieblemont C, Solal-Celigny P, Haioun C, Bouabdallah R, Lamy T, Milpied N, Gouill SL, Feugier P, Wenger MK, Wassner-Fritsch E, Asikanius E, Salles GA (2011) Encouraging activity of obinutuzumab (GA101) monotherapy in relapsed/refractory aggressive non-Hodgkin’s lymphoma: results from a phase II study (BO20999) [abstract]. Blood 118(21):3655Google Scholar
  40. 40.
    Brown JR, O’Brien S, Kingsley CD, Eradat H, Pagel JM, Lymp J, Hirata J, Kipps TJ (2013) Safety and efficacy of obinutuzumab (GA101) with fludarabine/cyclophosphamide (G-FC) or bendamustine (G-B) in the initial therapy of patients with chronic lymphocytic leukemia (CLL): results from the phase Ib GALTON trial (GAO4779g) [abstract]. Blood 122(21):523Google Scholar
  41. 41.
    Sehn LH, Assouline SE, Stewart DA, Mangel J, Gascoyne RD, Fine G, Frances-Lasserre S, Carlile DJ, Crump M (2012) A phase 1 study of obinutuzumab induction followed by 2 years of maintenance in patients with relapsed CD20-positive B-cell malignancies. Blood 119(22):5118–5125. doi: 10.1182/blood-2012-02-408773 CrossRefPubMedGoogle Scholar
  42. 42.
    Salles G, Morschhauser F, Lamy T, Milpied N, Thieblemont C, Tilly H, Bieska G, Asikanius E, Carlile D, Birkett J, Pisa P, Cartron G (2012) Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood 119(22):5126–5132. doi: 10.1182/blood-2012-01-404368 CrossRefPubMedGoogle Scholar
  43. 43.
    Cartron G, de Guibert S, Dilhuydy MS, Morschhauser F, Leblond V, Dupuis J, Mahe B, Bouabdallah R, Lei G, Wenger M, Wassner-Fritsch E, Hallek M (2014) Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood 124(14):2196–2202. doi: 10.1182/blood-2014-07-586610 CrossRefPubMedGoogle Scholar
  44. 44.
    Morschhauser FA, Cartron G, Thieblemont C, Solal-Celigny P, Haioun C, Bouabdallah R, Feugier P, Bouabdallah K, Asikanius E, Lei G, Wenger M, Wassner-Fritsch E, Salles GA (2013) Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large b-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol 31(23):2912–2919. doi: 10.1200/JCO.2012.46.9585 CrossRefPubMedGoogle Scholar
  45. 45.
    Coiffier B, Radford J, Bosly A, Martinelli G, Verhoef G, Barca G, Davies A, Decaudin D, Gallop-Evans E, Padmanabhan-Iyer S, Van Eygen K, Wu KL, Gupta IV, Lin TS, Goldstein N, Jewell RC, Winter P, Lisby S, Study i (2013) A multicentre, phase II trial of ofatumumab monotherapy in relapsed/progressive diffuse large B-cell lymphoma. Br J Haematol 163(3):334–342. doi: 10.1111/bjh.12537 CrossRefPubMedGoogle Scholar
  46. 46.
    Ferrajoli A, Falchi L, O’Brien S, Wierda W, Faderl S, Smith SC, Ayala AB, Kantarjian HM, Keating MJ (2012) Combination of ofatumumab and lenalidomide in patients with relapsed chronic lymphocytic leukemia (CLL): results of a phase II trial [abstract]. Blood 120(21):720Google Scholar
  47. 47.
    Ghobrial IM, Kaufman JL, Siegel DS, Vij R, Badros A, Neuman L, Wong H, Anderl J, Savona M (2013) Clinical profile of single-agent modified-release oprozomib tablets in patients (PTS) with hematologic malignancies: updated results from a multicenter, open-label, dose escalation phase 1B/2 study [abstract]. Blood 122(21):3184Google Scholar
  48. 48.
    Davids MS, Roberts AW, Anderson MA, Pagel JM, Kahl BS, Gerecitano JF, Darden DE, Nolan CE, Gressick LA, Yang J, Chyla BJ, Busman TA, Graham AM, Cerri E, Enschede SH, Humerickhouse RA, Seymour JF (2012) The BCL-2-specific BH3-mimetic ABT-199 (GDC-0199) is active and well-tolerated in patients with relapsed non-Hodgkin lymphoma: interim results of a phase I study [abstract]. Blood 120(21):304Google Scholar
  49. 49.
    Davids MS, Seymour JF, Gerecitano JF, Kahl BS, Pagel JM, Wierda WG, Anderson MA, Darden DE, Nolan CE, Gressick LA, Yang J, Chyla BJ, Busman TA, Graham AM, Cerri E, Enschede SH, Humerickhouse RA, Roberts AW (2013) Updated results of a phase I first-in-human study of the BCL-2 inhibitor ABT-199 (GDC-0199) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) [abstract]. J Clin Oncol 31(15):8520Google Scholar
  50. 50.
    Davids MS, Seymour JF, Gerecitano JF, Kahl BS, Pagel JM, Wierda WG, Anderson MA, Rudersdorf N, Gressick LA, Montalvo NP, Yang J, Zhu M, Dunbar M, Cerri E, Enschede SH, Humerickhouse R, Roberts AW (2014) Phase I study of ABT-199 (GDC-0199) in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL): responses observed in diffuse large B-cell (DLBCL) and follicular lymphoma (FL) at higher cohort doses [abstract]. J Clin Oncol 32(15):8522Google Scholar
  51. 51.
    Seymour JF, Davids MS, Pagel JM, Kahl BS, Wierda WG, Puvvada S, Gerecitano JF, Kipps TJ, Anderson MA, Huang DCS, Rudersdorf N, Gressick LA, Montalvo NP, Yang J, Zhu M, Dunbar M, Cerri E, Enschede SH, Humerickhouse R, Roberts AW (2014) ABT-199 (GDC-0199) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL): high complete-response rate and durable disease control [abstract]. J Clin Oncol 32(15):7015Google Scholar
  52. 52.
    Cortez M (2013) AbbVie suspends five clinical trials of leukemia therapy. Bloomberg Business. Accessed April 29 2015
  53. 53.
    Moutouh-de Parseval LA, Weiss L, DeLap RJ, Knight RD, Zeldis JB (2007) Tumor lysis syndrome/tumor flare reaction in lenalidomide-treated chronic lymphocytic leukemia. J Clin Oncol 25(31):5047. doi: 10.1200/JCO.2007.14.2141 CrossRefPubMedGoogle Scholar
  54. 54.
    National Comprehensive Cancer Network NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin’s Lymphomas. Version 5.2014. Accessed November 1 2014
  55. 55.
    Fallon MJ, Heck JN (2014) Fatal Stevens-Johnson syndrome/toxic epidermal necrolysis induced by allopurinol-rituximab-bendamustine therapy J Oncol Pharm Pract:[Epub ahead of print]. doi:  10.1177/1078155214533368
  56. 56.
    TREANDA (bendamustine hydrochloride). Full Prescribing Information, Teva Pharmaceuticals USA, Inc., North Wales, PA, 2015Google Scholar
  57. 57.
    Ji J, Mould DR, Blum KA, Ruppert AS, Poi M, Zhao Y, Johnson AJ, Byrd JC, Grever MR, Phelps MA (2013) A pharmacokinetic/pharmacodynamic model of tumor lysis syndrome in chronic lymphocytic leukemia patients treated with flavopiridol. Clin Cancer Res 19(5):1269–1280. doi: 10.1158/1078-0432.CCR-12-1092 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Scott C. Howard
    • 1
    Email author
  • Steven Trifilio
    • 2
  • Tara K. Gregory
    • 3
  • Nadine Baxter
    • 4
  • Ali McBride
    • 5
  1. 1.University of Memphis, School of Health StudiesMemphisUSA
  2. 2.Northwestern Memorial HospitalChicagoUSA
  3. 3.Colorado Blood Cancer Institute at Presbyterian St. Luke’s Medical CenterDenverUSA
  4. 4.University of Arkansas for Medical Sciences, Myeloma InstituteLittle RockUSA
  5. 5.The University of Arizona Cancer CenterTucsonUSA

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