ONCAlert | 2017 NANETS Symposium

Hypogammaglobulinemia and Abiraterone Therapy for Metastatic Prostate Cancer

Chandra Diwakarla, BSc (Hons), MBBS; Ganesalingam Pranavan, MBBS; and Paul Gatenby, MBBS, PhD
Published Online: Nov 15,2016

Abstract


Patients receiving chemotherapy for various malignancies are at risk of immunosuppression, which can lead to infective complications resulting in delayed therapy and potential progression of disease. Newer agents are now available for the management of castrate-resistant, metastatic prostate cancer, which have shown improved outcomes in progression-free survival and overall survival, and are particularly advantageous in elderly patients who would not otherwise tolerate traditional chemotherapy. These agents work on steroidogenesis pathways and do not affect immune function. We describe 3 cases whereby significant septic complications occurred in the setting of abiraterone use that were associated with hypogammaglobulinemia.
 

Case 1


A 77-year-old gentleman who commenced abiraterone in September 2014 after developing castrate- resistant prostate cancer following prior antiandrogen therapy. He developed sepsis with minimal to no improvement despite empiric intravenous antibiotics. The patient ultimately required immunoglobulin therapy with intravenous Intragam (IVIg). He subsequently opted for palliation and died.
 

Case 2


A 73-year-old gentleman with castrate-resistant prostate cancer following antiandrogen therapy from 2006 to 2014. After beginning abiraterone in December 2014 he developed recurrent fevers requiring repeat admissions and was found to be hypogammaglobulinemic. He was started on IVIg with improvement in symptoms and has been able to continue abiraterone with ongoing IVIg support.
 

Case 3


A 78-year old gentleman with Gleason score 9 prostate cancer who responded well to abiraterone, but later presented with sepsis of unknown source and was subsequently found to be hypogammaglobulianemic.

Prostate cancer can now be treated with a wide range of options that are associated with improved outcomes. To date, there have not been any reported cases of immunodeficiency associated with newer available agents such as abiraterone. The above cases highlight the occurrence of infection secondary to hypogammaglobulinemia in patients being treated with abiraterone and may represent a complication that needs to be considered in an already vulnerable population.
 

Introduction


Prostate cancer is the most common solid organ malignancy in men in Australia.1 Androgens are the predominant growth factor for prostate cancer, and inhibition of androgenic pathways serves as the major focus for treatment of advanced disease. Metastatic prostate cancer progressing after initial hormonal manipulation ie, castrate-resistant disease, was traditionally treated with cytotoxic drugs that were associated with significant treatment-related toxicities. Novel anti-androgen agents such as abiraterone and enzalutamide have been demonstrated to improve survival in both the pre and post-chemotherapy setting2,3 and are considered to have a reasonable toxicity profile.

While traditional anti-androgen approaches have aimed at lowering androgen concentrations they often result in castrate-resistant/refractory disease. Newer agents such as abiraterone act by inhibiting enzymes expressed in testicular, adrenal, and prostatic tumor tissue, which would normally facilitate the conversion of pregnenolone and progesterone to their active derivatives, as well as allow for the formation of dehyroepiandrosterone (DHEA) and androstenedione, which are not only important androgens, but also function as precursors for testosterone. The inhibition of these processes by abiraterone has resulted in dramatic improvements when treating castrate-resistant disease, however, they are associated with cardiac and liver abnormalities. Apart from these side effects, abiraterone has been associated with other toxicities including sepsis, however, not in the context of immunosuppression via hypogammaglobulinemia.

The patient population most often treated with therapies like abiraterone are usually considered unfit to receive chemotherapy or have progressed through multiple previous lines of treatment, and may therefore represent a more vulnerable group in terms of risk of deterioration. Currently, these drugs have been accepted as the more tolerable approach for such patients, however, the cases discussed here describe 3 instances where recurrent infections occurred following commencement of abiraterone in which all patients were found to be hypogammaglobulinaemic.
 

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Hypogammaglobulinemia and Abiraterone Therapy for Metastatic Prostate Cancer
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