TOXICITIES WITH BRENTUXIMAB VEDOTIN

Toxicities from BV differ from other antibody therapy given the drug conjugation with a cytotoxic agent MMAE. Some of the more common toxicities include neuropathy and neutropenia. Over 50% of patients experience peripheral neuropathy when given as monotherapy and 25% with combination treatment, with most cases being grade one and two.14,52 Most commonly, the median time to onset is around 12 weeks or after four cycles of treatment. The majority of patients improve after dose holding or dose reduction with resolution typically occurring within 12 weeks. Neutropenia occurs in approximately 20% of patients, typically at grade 3 or higher but is often transient.14,52 Dose delays occurred in 15% of patients but no increase in febrile neutropenia was seen. IRRs are seen within the first 1–2 cycles and typically occur in over 50% of patients but are only considered serious in 15% of patients. Rash can be seen in about 10–30% of patients and more serious events such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very rare occurring at a rate less than 0.1%.53 Besides SJS and TEN, other rare but serious adverse events include: progressive multifocal leukoencephalopathy, pancreatitis, pulmonary toxicity, and hepatoxicity. The pulmonary toxicity is significantly more common when used in combination with ABVD and for this reason the use of BV with bleomycin is contraindicated.53

CONCLUSION


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A greater understanding of the pathophysiology of classical Hodgkin lymphoma has enabled researchers to identify and develop effective targeted therapies that have improved outcomes for patients. These novel agents have addressed an unmet need, particularly in the relapsed setting after ASCT. The CD30-directed antibody-drug conjugate, BV, was the first to be approved for these patients with an otherwise dismal prognosis. The addition of BV to established chemotherapy regimens for cHL has shown great promise as a bridge to ASCT and eventually led to its current front-line approval with AVD. Unfortunately, the clinical benefit of AAVD is relatively modest over ABVD, restricted to a select sub-population, and associated with significantly increased toxicity. BV may benefit a broader population by allowing for reduced cycles or even omission of other cytotoxic chemotherapeutics, however, longer follow up of the previously mentioned and ongoing studies is necessary to answer these questions. Additionally, the incorporation of immune checkpoint inhibition provides an opportunity to offer a more targeted approach and potentially eliminate conventional chemotherapy. Next steps in clinical investigation need to more clearly define where BV belongs within the treatment algorithm, recognizing this ought to be tailored to patient-specific features such as age, stage, and prognostic features. Although cHL has traditionally been considered a favorable malignancy, it is imperative to continue research efforts into unique trial designs and strategies to further the field and benefit future patients.

Disclosure

The authors report no conflicts of interest in this work.


Catherine Lai,1 Adrese Michael Kandahari,1 Chaitra Ujjani2

1Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, DC, USA; 2Seattle Cancer Care Alliance, Fred Hutchinson CRC, University of Washington, Seattle, WA, USA

Correspondence: Catherine Lai
Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, DC, USA
Tel +1-202-444-3735
Fax +1-202-444-0939
Email [email protected]


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Source: Blood and Lymphatic Cancer: Targets and Therapy.
Originally published December 9, 2019.

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