INFECTIOUS RISKS AND COMPLICATIONS IN ADULT LEUKEMIC PATIENTS RECEIVING BLINATUMOMAB

Main Article Content

Wonhee So *
Shuchi Pandya
Rod Quilitz
John Greene
(*) Corresponding Author:
Wonhee So | wonhee.so@moffitt.org

Abstract

Background: Blinatumomab is an anti-CD19 immunotherapy approved for relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) with significantly increased survival rate. While blinatumomab showed lower rates of infection, neutropenia and mucosal barrier injury versus chemotherapy, its infection risks are not well described.

Methods: All patients who received blinatumomab for ≥ 7 days at an academic cancer center from May 2015 to April 2017 were included. Patient characteristics pertinent to infectious risks and complications were examined.

Results: Twenty patients with refractory (25%), relapsed (70%), or remitted (5%) B-ALL who received a total of 35 cycles were included. Ten of the 35 cycles were interrupted, none of which were due to infections. Twenty six infections (n) were observed with lower respiratory (9), gastrointestinal (6) and bacteremia (5) being most common. Compared to patients without nodular, possible mold pneumonia (n=16), patients with nodular pneumonia (n=4) had significantly lower baseline absolute neutrophil count (ANC) (2319 v. 208/µL, p=0.011). There were no differences in baseline characteristics including ANC between bacteremic and non-bacteremic patients. One patient was discharged with no antibacterial prophylaxis since ANC recovered to >500cells/µL, but developed Pseudomonal bacteremia within a week with ANC ~100cells/µL.

Conclusion: Despite blinatumomab’s relatively modest myelosuppression and the lack of mucotoxicity, host factors (e.g., duration and degree of neutropenia/lymphopenia) play a key role and should be considered when choosing anti-microbial prophylaxis. In relapsed/refractory disease, the ANC should be monitored closely post blinatumomab since neutropenia can unexpectedly develop after treatment which may be compounded by the underlying disease and recent chemotherapy effects.


Downloads month by month

Downloads

Download data is not yet available.

Article Details

References

1. Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foa R, Bassan R, Arslan O, Sanz MA, BergeronJ, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Bruggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 2017;376:836-47.

2. Topp MS, Gokbuget N, Stein AS, Zugmaier G, O’Brien S, Bargou RC, Dombret H, Fielding AK, Heffner L, Larson RA, Neumann S, Foa R, Litzow M, Ribera JM, Rambaldi A, Schiller g, Bruggermann M, Horst HA, Holland C, Jia C, Maniar T, Huber B, NagorsenD, Forman SJ, Kantarjian HM. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicenter, single-arm, phase 2 study. Lancet Oncol 2015;16:57-66.

3. Supplement to: Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foa R, Bassan R, Arslan O, Sanz MA, BergeronJ, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Bruggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus chemotherapy for advanced acute
lymphoblastic leukemia. N Engl J Med 2017;376:836-47

4. Protocol Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foa R, Bassan R, Arslan O, Sanz MA, BergeronJ, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Bruggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 2017;376:836-47.

5. National Comprehensive Cancer Network. Prevention and treatment of cancer-related infections. https://www.nccn.org/professionals/physician_gls/pdf/infections.pdf. Accessed Nov 2, 2017.

6. Greene R. The radiological spectrum of pulmonary aspergillosis. Med Mycol 2005;43 Suppl 1:S147-54.

7. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Muñoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46:1813-21.

8. Bitar D, Lortholary O, Le Strat Y, Nicolau J, Coignard B, Tattevin P, Che D, Dromer F. Population-based analysis of invasive fungal infections. France, 2001-2010. Emerg Infect Dis 2014;20:1149-55.

9. Azie N, Neofytos D, Pfaller M, Meier-Kriesche HU, Quan SP, Horn D. The PATH (Prospective antifungal therapy) Alliance® registry and invasive fungal infections: update 2012. Diagn Microbiol Infect Dis 2012;73:293-300.

10. Gerson SL, Talbot GH, Hurwitz S, Strom BL, Lusk EJ, Cassileth PA. Prolonged granulycytopenia: the major risk factor for invasive pulmonary aspergillosis in patients with acute leukemia. Ann Intern med 1984:100:345-51.

11. Lass-Florl C, Roilides E, Loffler J, Wilflingseder D, Romani L. Minireview: host defense in invasive aspergillosis. Mycoses 2013;56:403-13.

12. Kurosawa M, Yonezumi M, Hashino S, Tanaka J, Nishio M, Kaneda M, Ota S, Koda K, Suzuki N, Yoshida M, Hirayama Y, Takimoto R, Torimoto Y, Mori A, Takahashi T, Iizuka S, Ishida T, Kobayashi R, Oda T, Sakai H, Yamamoto S, Takahashi F, Fukuhara T. Epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies. Int J Hematol 2012;96:748-57.

13. Sun Y, Huang H, Chen J, Li J, Ma J, Li J, Liang Y,
Wang J, Li Y, Yu K, Hu J, Jin J, Wang C, Wu D, Xiao Y, Huang X. Invasive fungal infection in patients receiving chemotherapy for hematological malignancy: a multicenter, prospective, observational study in China. Tumour Biol 2015;36:757-67.

14. Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, Martino B, Pastore D, Picardi M, Bonini A, Chierichini A, Fanci R, Caramatti C, Invernizzi R, Mattei D, Mitra ME, Melillo L, Aversa F, Van Lint MT, Falcucci P, Valentini CG, Girmenia C, Nosari A. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica 2006;91:1068-75.

15. Auberger J, Lass-Florl C, Ulmer H, Nogler-Semenitz E, Clausen J, Gunsilius E, Einsele H, Gastl G, Nachbaur D. Significant alterations in the epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies. Int J Hematol 2008;88:508-15.

16. Van der Velden WJ, Herbers AH, Netea MG, Blijlevens NM. Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis. Br J Haematol 2014;167:441-52.

17. Lewis V, Yanofsky R, Mitchell D, Dix D, Ethier MC, Gillmeister B, Johnston D, Michon B, Stobart K, Portwine C, Silva M, Cellot S, Price V, Bowes L, Zelcer S, Brossard J, Beyene J, Sung L. Predictors and outcomes of viridans group streptococcal infections in pediatric acute myeloid leukemia: from the Canadian infections in AML research group. Pediatr Infect Dis J. 2014;33:126-9.

18. Girmenia C, Bertaina A, Piciocchi A, Perruccio K, Algarotti A, Busca A, Cattaneo C, Raiola AM, Guidi S, Iori AP, Candoni A, Irrera G, Milone G, Marcacci G, Scimè R, Musso M, Cudillo L, Sica S, Castagna L, Corradini P, Marchesi F, Pastore D21, Alessandrino EP, Annaloro C, Ciceri F, Santarone S, Nassi L, Farina C, Viscoli C, Rossolini GM, Bonifazi F, Rambaldi A; Gruppo Italiano Trapianto di Midollo Osseo (GITMO) and Associazione Microbiologi Clinici Italiani (AMCLI). Incidence, risk factors and outcome of pre-engraftment Gram-negative bacteremia after allogeneic and autologous hematopoietic stem cell transplantation: an Italian prospective multicenter survey. Clin Infect Dis 2017; 65:1884-96. doi: 10.1093/cid/cix690.

19. De Rosa FG, Motta I, Audisio E, Frairia C, Busca A, Di Perri G, Marmont F. Epidemiology of bloodstream infections in patients with acute myeloid leukemia undergoing levofloxacin prophylaxis. BMC Infect Dis 2013;13:563-7.

20. Patterson TF, Thompson III GR, Denning DW, Fishman JA, Hadley S, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Nguyen MH, Segal BH, Steinbach WJ, Stevens DA, Walsh TJ, Wingard JR, Young JA, Bennett JE. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the infectious diseases society of America. Clin Infect Dis 2016;63:433-42.

21. Maertens JA, Blennow O, Duarte RF, Muñoz P. The current management landscape: aspergillosis. J Antimicrob Chemother 2016;71 (suppl2):ii23-ii29.