D3.276 - Acalabrutinib as premedication in platinum agents desensitization protocols: a case series supporting its role in enhancing tolerance with a repeatible efficacity

The mechanisms underlying immediate hypersensitivity to platinum agents involve IgE- and non-IgE mediated responses as well as cytokine release, particularly IL-6 and TNF-alpha. Current desensitization protocols aim to address these mechanisms to achieve temporary tolerance, with success rates ranging from 58% to 100%. To manage breakthrough reactions occurring during desensitization, premedication strategies, including the use of omalizumab, have been documented in case series. A recent case report highlighted a patient successfully receiving oxaliplatin after being premedicated 48 hours prior with acalabrutinib, whose skin tests (STs) to oxaliplatin became negative while under acalabrutinib. Compared to omalizumab which has a half-life of 26 days, acalabrutinib has a much shorter half-life of 0.9 hours, making it convenient and potentially safer to administer shortly before exposure to platinum agents. However, to the author’s knowledge, the use of acalabrutinib in desensitization protocols to platinum agents is mainly based on this single case report.

Retrospective case series involving two patients referred to the Allergy Unit of the University Hospital of Tours for allergy investigations and management between October and December 2024. Both patients had a history of severe anaphylaxis (grade III) that occurred during the second cycle of treatment with a platinum agent.

Both patients underwent a classic desensitization protocol but developed breakthrough reactions (grade III and grade I, respectively). Serum tryptase levels indicated mast cell degranulation during these reactions, increasing from 4.08 to 11.8 mcg/L (for the grade III reaction) and from 3.53 to 7.66 mcg/L (for the grade I reaction). One patient had positive STs to carboplatin performed before acalabrutinib. The other patient underwent STs after the start of acalabrutinib, with a four-week gap since the last exposure. His STs were negative, potentially indicating an impact of acalabrutinib on longer-term immune tolerance. Both patients received acalabrutinib as premedication 48h, 24h before and on the day of desensitization to platinum agents which allowed them to successfully complete subsequent chemotherapy cycles (four for the first and two for the second patient) without adverse events or organ impairment resulting from acalabrutinib.

This case series supports the potential of acalabrutinib as premedication for patients experiencing breakthrough reactions to platinum agents, allowing a sustained and safe continuation of chemotherapy.