Results

Conclusion

Disclosures

LimitationsMethods

Purpose

Background

Etanercept for the treatment of pulmonary complications after hematopoietic stem cell transplantation

Jeremy R. DeGrado PharmD BCPS1, Kelly Babcock PharmD Candidate2, Kevin E. Anger PharmD BCPS1, Paul M. Szumita PharmD BCPS1

1Department of Pharmacy Brigham and Women’s Hospital, Boston, MA2Northeastern University, Boston, MA

Hematopoietic stem cell transplantation (HSCT) is an important therapy in the treatment of both malignant and non-malignant disorders

Pulmonary complications following HSCT include various noninfectious conditions, such as idiopathic pneumonia syndrome (IPS), diffuse alveolar hemorrhage (DAH), and cryptogenic organizing pneumonia (COP)

The exact pathogenesis of many of these pulmonary complications is unknown, but may involve immunologic factors and cytokines, such as tumor necrosis factor-α1

Pulmonary dysfunction occurs in up to 55% of transplant recipients and mortality remains high, ranging between 50 to 90%1,2

Treatment often involves mechanical ventilation and high dose corticosteroids, although their efficacy has not been established3

The use of etanercept in addition to corticosteroids has been encouraging in some smaller studies, but prospective studies are lacking2,4

To evaluate the safety of etanercept in patients with pulmonary complications following HSCT

The authors of this presentation have no disclosures concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation

References

Both hospital and long-term mortality were high and consistent with previous studies

The incidence and severity of suspected adverse drug events following the initiation of etanercept is noteworthy

Prospective, randomized data are needed to weigh the risks of etanercept against the possible benefits in patients with pulmonary complications following HSCT

Single center, retrospective analysis

Incomplete data to determine effects on pulmonary parameters

Small sample size

1. Yen KT, Lee KS, Krowka MJ, Burger CD. Pulmonary complications in bone marrow transplantation: a practical approach to diagnosis and treatment. Clin Chest Med. 2004;25:189-201

2. Yanik GA, Ho VT, Levine JE, et al. The impact of soluble tumor necrosis factor receptor etanercept on the treatment of idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation. Blood. 2008;112:3073-3081

3. Lara AR, Schwarz MI. Diffuse alveolar hemorrhage. Chest. 2010;137:1164-71

4. Yanik G, Hellerstedt B, Custer J, et al. Etanercept (Enbrel) administration for idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2002;8:395-400

Single center, retrospective cohort analysis at a tertiary academic medical center

Approval obtained from institutional review board

A hospital database was used to identify all adult patients who received etanercept from 2005 to 2010

Patient Enrollment

353

HARVARD MEDICAL SCHOOL TEACHING AFFILIATE

83 patients ordered for etanercept

17 patients included

66 cases excluded

• 62 had other indication

• 3 never received

• 1 enrolled in other etanercept study

Outcomes assessed included baseline demographics, number of infections, type of infections, adverse drug events, ICU and hospital lengths of stay, and survival

Diagnosis of “infection” required both documentation of proven or suspected infection as well as a positive culture, viral load, or fungal marker

Inclusion criteria: Age ≥ 18

Suspected pulmonary complication s/p HSCT

Included IPS, DAH, or COP

Exclusion criteria:

Etanercept for any other indication

Patient involvement in any other study

Baseline Characteristics

VariablePatients(n = 17)

Age, years* 42.9 ± 12.2

Male‡ 13 (76)

Height, inches* 68.4 ± 4.4

Actual Body Weight, kg* 81.9 ± 18.6

Ideal Body Weight, kg* 67.8 ± 11.7

BMI, kg/m2* 27.1 ± 5.1

APACHE II*α 22.3 ± 8.9

Serum creatinine, mg/dL* 1.2 ± 0.9

WBC, 103/µL* 8.7 ± 6.2

Platelets, 103/µL* 95.5 ± 82.6

Tbili, mg/dL* 1.8 ± 2.5

PaO2/FiO2* 96.7 ± 39.8

Mechanical ventilation‡ 14 (82.3)

Pulmonary complication‡

IPS 10 (58.9)

DAH 5 (29.4)

COP 2 (11.7)

Hematologic diagnosis‡

AML 7 (53.8)

MDS 3 (17.6)

ALL 2 (11.8)

Hodgkins lymphoma 2 (11.8)

Otherβ 3 (17.6)

Donor type‡

URD 11 (64.7)

MRD 5 (29.4)

Autologous 1 (5.9)

Medications‡

Tacrolimus 11 (64.7)

Sirolimus 7 (53.8)

Mycophenolate 10 (58.9)

Cyclosporine 2 (11.8)

Steroids 16 (94.1)

Vasoactive agents 10 (58.9)* Mean ± SD; ‡ n (%); α n=13 patients; β progressive multifocal leukencephelopathy (n=1), common variable immunodeficiency (n=1), polycythemia vera (n=1)IPS = idiopathic pneumonia syndrome; DAH = diffuse alveolar hemorrhage; COP = cryptogenic organizing pneumonia; AML = acute myeloid leukemia; MDS = myelodysplastic syndrome; ALL = acute lymphoblastic leukemia; URD = unrelated donor; MRD = matched related donor

Drug Treatment Characteristics

Patients(n = 17)

Initiated etanercept in ICU‡ 13 (76.4)

Time from HSCT to etanercept, days* 249 ± 196

Number of doses* 3.4 ± 2.4* Mean ± SD; ‡ n (%)

Results

Suspected Adverse Drug Events

Patients(n = 17)

Patients with documented infection‡ 4 (23.6)

Total number of infections 5

Pathogen isolated

Fungal 2

Bacterial 2

Viral 1

Time from etanercept initiation to infection, days* 23.8 ± 13.3

Patients with skin reaction‡ 2 (11.7)

TEN 1 Rash 1Mean ± SD; ‡ n (%)TEN = Toxic Epidermal Necrosis

Patient Outcomes

Patients(n = 17)

ICU length of stay, days* 21 ± 20

Hospital length of stay, days* 37 ± 24

ICU survival‡ 4 (23.5)

Hospital survival‡ 4 (23.5)

Survival at 100 days‡ 3 (17.6)

Survival at 1 year‡ 3 (17.6)* Mean ± SD; ‡ n (%)