EVALUATION OF ADVERSE EFFECTS OF IBRUTINIB: EXPERIENCE FROM A NORTHERN HOSPITAL OF SPAIN
Author(s): ,
Laura Escalada González
Affiliations:
Haematology and hemotherapy service,Hospital Universitario Central de Asturias,Oviedo,Spain
,
Paula López de Ugarriza
Affiliations:
Haematology and hemotherapy service,Hospital Universitario Central de Asturias,Oviedo,Spain
,
María Ángeles Fernández Rodríguez
Affiliations:
Haematology and hemotherapy service,Hospital Universitario Central de Asturias,Oviedo,Spain
Ángel Ramírez Páyer
Affiliations:
Haematology and hemotherapy service,Hospital Universitario Central de Asturias,Oviedo,Spain
EHA Library. Escalada González L. 06/09/21; 324186; PB1507
Laura Escalada González
Laura Escalada González
Contributions
Abstract

Abstract: PB1507

Type: Publication Only

Session title: Chronic lymphocytic leukemia and related disorders - Clinical

Background

Ibrutinib has emerged as an effective therapeutic alternative with proven clinical benefit in several lymphoid neoplasms such as Chronic Lymphatic Leukemia (CLL), Mantle Cell Lymphoma (MCL), and Waldenström's Macroglobulinemia (WM). However, it can produce adverse effects that may limit its use.

Aims

To evaluate the clinical impact and adverse effects/toxicity of Ibrutinib in patients diagnosed with CLL, MCL and WM, who were treated with this drug between 2015 and 2020 at our hospital.

Methods

An observational study in which 41 patients diagnosed with CLL, MCL and WM and treated with Ibrutinib, were included.

Results

41 people were enrolled: 36 CLL (88%), 4 MCL (10%) and 1 WM (2%). 63% were men and 49% were patients aged >74 years. From the total number of patients, 8 (20%) have died (5 LLC, 2 LCM and 1 WM).


Comorbidities at diagnosis were: 18 patients (44%) had arterial hypertension, 7 (17%) had diabetes mellitus, and 5 (12%) had dyslipidemia. 6 patients had cardiovascular alterations: 3 (7%) Atrial Fibrillation (AF), 2 (5%) dilated cardiomyopathy and 1 (2%) heart failure; 8 patients (19%) had respiratory disorders and 5 (12%) previous tumors (3 malignant and 2 benign).


In the subgroup of patients with CLL, 25% were Rai-Binet advanced stage and 42% had high-risk cytogenetic alterations (del17p / TP53 / del11q). 36% received Ibrutinib as the first line and 64% had relapsed CLL. The median duration of treatment in these patients was 19.5 months (range from 3 to 36 months). 5 CLL have received post-Ibrutinib treatment because of the progression of the disease.


Patients with MCL were all stage IV: 75% received Ibrutinib in the second line and 25% received it in the third line (25%). The patient with WM received Ibrutinib in the second line.


ADVERSE EFFECTS


17 patients (41%) had infectious complications (mostly relapsing CLL): 10 respiratory (3 of them were severe because of H. influenzae, K. pneumoniae and Varicella-Zoster Virus (VZV). 3 encephalitis (1 tuberculous, 1 viral because of VZV and 1 case in which the implicated microorganism was not identified), 2 urinary (E. coli), 1 digestive (Campylobacter jejuni) and 1 cutaneous (cellulitis due to S. pyogenes). In 4 CLL (24%), these infections led to the temporary suspension of the drug for an average of 13.5 days (range: 10-16 days) and in 2 CLL (12%), the infections caused the definitive suspension by the appearance of CNS involvement.


3 patients have suffered grade IV bleeding complications: 2 CLL required temporary suspension and 1 WM required definitive suspension because of subdural hematomas.


1 CLL and 1 WM developed AF, 1 CLL grade II hyponatremia and 1 CLL and 1 MCL, grade IV hyponatremia (definitive suspension). 1 LLC required a temporary suspension of Ibrutinib due to grade IV pancytopenia and edema. There was 1 CLL that developed a secondary lung neoplasm.


In conclusion, in 7 patients (17%) it was necessary to discontinue the drug (2 of them required a dose adjustment when restarting the drug) and in 5 patients (12%), Ibrutinib was permanently suspended.


8 patients died (all of them were older than 75 years and had comorbidities). 5 died due to adverse effects: 3 infectious complications (2 CLL and 1 MCL), 1 WM with grade IV hemorrhage, and 1 CLL due to secondary carcinoma.

Conclusion

In our experience, infectious complications were the most frequent and caused discontinuations and temporary suspensions of Ibrutinib in most cases. However, there was little impact of bleeding complications, hematological adverse effects and new cases of AF. Generally, Ibrutinib is a well-tolerated and effective drug.

Keyword(s): Adverse reaction, Chronic lymphocytic leukemia, Ibrutinib, Mantle cell lymphoma

Abstract: PB1507

Type: Publication Only

Session title: Chronic lymphocytic leukemia and related disorders - Clinical

Background

Ibrutinib has emerged as an effective therapeutic alternative with proven clinical benefit in several lymphoid neoplasms such as Chronic Lymphatic Leukemia (CLL), Mantle Cell Lymphoma (MCL), and Waldenström's Macroglobulinemia (WM). However, it can produce adverse effects that may limit its use.

Aims

To evaluate the clinical impact and adverse effects/toxicity of Ibrutinib in patients diagnosed with CLL, MCL and WM, who were treated with this drug between 2015 and 2020 at our hospital.

Methods

An observational study in which 41 patients diagnosed with CLL, MCL and WM and treated with Ibrutinib, were included.

Results

41 people were enrolled: 36 CLL (88%), 4 MCL (10%) and 1 WM (2%). 63% were men and 49% were patients aged >74 years. From the total number of patients, 8 (20%) have died (5 LLC, 2 LCM and 1 WM).


Comorbidities at diagnosis were: 18 patients (44%) had arterial hypertension, 7 (17%) had diabetes mellitus, and 5 (12%) had dyslipidemia. 6 patients had cardiovascular alterations: 3 (7%) Atrial Fibrillation (AF), 2 (5%) dilated cardiomyopathy and 1 (2%) heart failure; 8 patients (19%) had respiratory disorders and 5 (12%) previous tumors (3 malignant and 2 benign).


In the subgroup of patients with CLL, 25% were Rai-Binet advanced stage and 42% had high-risk cytogenetic alterations (del17p / TP53 / del11q). 36% received Ibrutinib as the first line and 64% had relapsed CLL. The median duration of treatment in these patients was 19.5 months (range from 3 to 36 months). 5 CLL have received post-Ibrutinib treatment because of the progression of the disease.


Patients with MCL were all stage IV: 75% received Ibrutinib in the second line and 25% received it in the third line (25%). The patient with WM received Ibrutinib in the second line.


ADVERSE EFFECTS


17 patients (41%) had infectious complications (mostly relapsing CLL): 10 respiratory (3 of them were severe because of H. influenzae, K. pneumoniae and Varicella-Zoster Virus (VZV). 3 encephalitis (1 tuberculous, 1 viral because of VZV and 1 case in which the implicated microorganism was not identified), 2 urinary (E. coli), 1 digestive (Campylobacter jejuni) and 1 cutaneous (cellulitis due to S. pyogenes). In 4 CLL (24%), these infections led to the temporary suspension of the drug for an average of 13.5 days (range: 10-16 days) and in 2 CLL (12%), the infections caused the definitive suspension by the appearance of CNS involvement.


3 patients have suffered grade IV bleeding complications: 2 CLL required temporary suspension and 1 WM required definitive suspension because of subdural hematomas.


1 CLL and 1 WM developed AF, 1 CLL grade II hyponatremia and 1 CLL and 1 MCL, grade IV hyponatremia (definitive suspension). 1 LLC required a temporary suspension of Ibrutinib due to grade IV pancytopenia and edema. There was 1 CLL that developed a secondary lung neoplasm.


In conclusion, in 7 patients (17%) it was necessary to discontinue the drug (2 of them required a dose adjustment when restarting the drug) and in 5 patients (12%), Ibrutinib was permanently suspended.


8 patients died (all of them were older than 75 years and had comorbidities). 5 died due to adverse effects: 3 infectious complications (2 CLL and 1 MCL), 1 WM with grade IV hemorrhage, and 1 CLL due to secondary carcinoma.

Conclusion

In our experience, infectious complications were the most frequent and caused discontinuations and temporary suspensions of Ibrutinib in most cases. However, there was little impact of bleeding complications, hematological adverse effects and new cases of AF. Generally, Ibrutinib is a well-tolerated and effective drug.

Keyword(s): Adverse reaction, Chronic lymphocytic leukemia, Ibrutinib, Mantle cell lymphoma

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