Severe infections in patients with lymphoproliferative diseases treated with new targeted drugs: A multicentric real-world study.

Adenine / adverse effects Adolescent Adult Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors Aged Aged, 80 and over Antibodies, Monoclonal, Humanized / adverse effects Antineoplastic Agents, Immunological / adverse effects Benzamides / adverse effects Bridged Bicyclo Compounds, Heterocyclic / adverse effects Female Humans Immunocompromised Host Infections / etiology Lymphopenia / complications Lymphoproliferative Disorders / complications Male Middle Aged Piperidines / adverse effects Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors Purines / adverse effects Pyrazines / adverse effects Quinazolinones / adverse effects Retrospective Studies Risk Factors Sulfonamides / adverse effects Young Adult

infectious diseases infectious risk lymphoproliferative disease prophylaxis targeted drugs

Journal

Cancer medicine

ISSN: 2045-7634

Titre abrégé: Cancer Med

Pays: United States

ID NLM: 101595310

Informations de publication

Date de publication:
11 2021

Historique:

revised: 04 08 2021

received: 07 05 2021

accepted: 26 08 2021

pubmed: 25 9 2021

medline: 18 3 2022

entrez: 24 9 2021

Statut: ppublish

Résumé

Lymphoid neoplasms treatment has recently been renewed to increase antitumor efficacy and conventional chemotherapies toxicities. Limited data have been published about the infection risk associated with these new drugs, therefore this study analyzes the infectious complications in patients with lymphoproliferative diseases (LPD) treated with monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, nivolumab, or pembrolizumab), BTK inhibitors (ibrutinib and acalabrutinib), PI3K inhibitors (idelalisib) and BCL2 inhibitors (venetoclax). Multicenter retrospective study of 458 LPD patients treated with targeted therapies in real-life setting, in 18 Spanish institutions, from the time of their commercial availability to August 2020. Severe infections incidence was 23% during 17-month median follow-up; cumulative incidence was higher in the first 3-6 months of targeted drug treatment and then decreased. The most frequent etiology was bacterial (54%). Nine (6%) Invasive fungal infections (IFI) were observed, in its majority in chronic lymphocytic leukemia (CLL) patients treated predominantly with ibrutinib. Significant risk factors for severe infection were: severe lymphopenia (p = 0.009, OR 4.7, range 1.3-1.7), combined targeted treatment vs single agent treatment (p = 0.014 OR 2.2 range 1.1-4.2) and previous rituximab (p = 0.03 OR 1.8, range 1.05-3.3). Infection-related mortality was 6%. In 22% of patients with severe infections, definitive discontinuation of the targeted drug was observed. A high proportion of patients presented severe infections during follow-up, with non-negligible attributable mortality, but infection incidence is not superior to the one observed during the chemotherapy era. In selected cases with specific risk factors for infection, antimicrobial prophylaxis should be considered.

Sections du résumé

BACKGROUND

METHODS

Multicenter retrospective study of 458 LPD patients treated with targeted therapies in real-life setting, in 18 Spanish institutions, from the time of their commercial availability to August 2020.

RESULTS

Severe infections incidence was 23% during 17-month median follow-up; cumulative incidence was higher in the first 3-6 months of targeted drug treatment and then decreased. The most frequent etiology was bacterial (54%). Nine (6%) Invasive fungal infections (IFI) were observed, in its majority in chronic lymphocytic leukemia (CLL) patients treated predominantly with ibrutinib. Significant risk factors for severe infection were: severe lymphopenia (p = 0.009, OR 4.7, range 1.3-1.7), combined targeted treatment vs single agent treatment (p = 0.014 OR 2.2 range 1.1-4.2) and previous rituximab (p = 0.03 OR 1.8, range 1.05-3.3). Infection-related mortality was 6%. In 22% of patients with severe infections, definitive discontinuation of the targeted drug was observed.

CONCLUSION

A high proportion of patients presented severe infections during follow-up, with non-negligible attributable mortality, but infection incidence is not superior to the one observed during the chemotherapy era. In selected cases with specific risk factors for infection, antimicrobial prophylaxis should be considered.

Identifiants

DOI: 10.1002/cam4.4293 PMID: 34558211 PMC: PMC8559487

pubmed: 34558211

doi: 10.1002/cam4.4293

pmc: PMC8559487

doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0

Antineoplastic Agents, Immunological 0

BCL2 protein, human 0

Benzamides 0

Bridged Bicyclo Compounds, Heterocyclic 0

Piperidines 0

Proto-Oncogene Proteins c-bcl-2 0

Purines 0

Pyrazines 0

Quinazolinones 0

Sulfonamides 0

ibrutinib 1X70OSD4VX

Agammaglobulinaemia Tyrosine Kinase EC 2.7.10.2

BTK protein, human EC 2.7.10.2

acalabrutinib I42748ELQW

Adenine JAC85A2161

venetoclax N54AIC43PW

idelalisib YG57I8T5M0

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

Pagination

7629-7640

Informations de copyright

Références

Cancer. 2013 Nov 1;119(21):3805-11

pubmed: 23943357

Lancet Oncol. 2016 Sep;17(9):1283-94

pubmed: 27451390

Leuk Lymphoma. 2018 Mar;59(3):625-632

pubmed: 28696801

Lancet. 2018 Feb 17;391(10121):659-667

pubmed: 29241979

Haematologica. 2017 Apr;102(4):e156-e159

pubmed: 27979923

Am J Infect Control. 1988 Jun;16(3):128-40

pubmed: 2841893

Am J Hematol. 2018 Jan;93(1):E24-E27

pubmed: 29055105

Curr Hematol Malig Rep. 2019 Jun;14(3):197-205

pubmed: 31028669

Leukemia. 2019 Oct;33(10):2527-2530

pubmed: 31086260

Cancer Cell. 2017 Jun 12;31(6):731-733

pubmed: 28552326

J Hematol Oncol. 2016 Mar 09;9:21

pubmed: 26957112

Hematol Oncol. 2018 Feb;36(1):128-135

pubmed: 28639416

JAMA Oncol. 2020 Feb 1;6(2):248-254

pubmed: 31855259

Blood Rev. 2018 Sep;32(5):387-399

pubmed: 29571669

Med Mal Infect. 2018 Jun;48(4):294-297

pubmed: 29402474

Blood. 2013 Oct 10;122(15):2539-49

pubmed: 23886836

N Engl J Med. 2015 Jan 22;372(4):311-9

pubmed: 25482239

Blood. 2015 Nov 5;126(19):2213-9

pubmed: 26337493

Blood. 2018 Apr 26;131(17):1987-1989

pubmed: 29490923

Br J Clin Pharmacol. 2021 Mar;87(3):895-904

pubmed: 32559327

Leuk Lymphoma. 2020 Oct;61(10):2292-2294

pubmed: 32701043

Leuk Lymphoma. 1994 Apr;13(3-4):203-14

pubmed: 8049645

Cancer Med. 2021 Nov;10(21):7629-7640

pubmed: 34558211

Respir Med Case Rep. 2017 Mar 20;21:27-29

pubmed: 28377877

Med Clin (Barc). 2020 Feb 14;154(3):101-107

pubmed: 31771856

N Engl J Med. 2018 Jan 25;378(4):331-344

pubmed: 29224502

Leuk Lymphoma. 2020 Oct;61(10):2375-2382

pubmed: 32508208

Blood Rev. 2017 Mar;31(2):17-29

pubmed: 27682882

Lancet Oncol. 2016 Jun;17(6):768-778

pubmed: 27178240

Bone Marrow Transplant. 2010 Feb;45(2):339-47

pubmed: 19561648

Clin Microbiol Infect. 2018 Jun;24 Suppl 2:S83-S94

pubmed: 29572070

Leuk Lymphoma. 2020 Dec;61(12):3002-3005

pubmed: 32611212

Leuk Lymphoma. 2017 Dec;58(12):2981-2982

pubmed: 28554246

Ann Hematol. 2015 Aug;94(8):1419-20

pubmed: 25903044

Blood Rev. 2020 Mar;40:100635

pubmed: 31699465

Leuk Lymphoma. 2017 Aug;58(8):1973-1976

pubmed: 27960571

N Engl J Med. 2017 Oct 5;377(14):1331-1344

pubmed: 28976863

Hematol Oncol. 2017 Dec;35(4):925-928

pubmed: 27641225

Lancet. 2019 Jan 19;393(10168):229-240

pubmed: 30522922

Haematologica. 2017 Mar;102(3):e108-e111

pubmed: 27856512

Leuk Lymphoma. 2018 Dec;59(12):2792-2800

pubmed: 29764250

Clin Infect Dis. 2018 Aug 16;67(5):687-692

pubmed: 29509845

Blood. 2014 May 29;123(22):3390-7

pubmed: 24615777

Clin Infect Dis. 2018 Jan 6;66(1):140-148

pubmed: 29029010

Blood. 2010 Sep 23;116(12):2078-88

pubmed: 20522708

Lancet Oncol. 2017 Feb;18(2):230-240

pubmed: 28089635

Leukemia. 2019 Apr;33(4):844-862

pubmed: 30700842

Lancet Oncol. 2016 Jul;17(7):928-942

pubmed: 27216274