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    Cutaneous adverse reactions in B-RAF positive metastatic melanoma following sequential treatment with B-RAF/MEK inhibitors and immune checkpoint blockade or vice versa. A single-institutional case-series

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    Author
    Naqash, Abdul Rafeh; File, Danielle M.; Ziemer, Carolyn M.; Whang, Young E.; Landman, Paula; Googe, Paul B.; Collichio, Frances A.
    Abstract
    Background With the advent of immune-checkpoint inhibitors and targeted treatments (TT), there have been unprecedented response rates and survival in advanced melanoma, but the optimal sequencing of these two treatments modalities is unknown. Combining or sequencing these agents could potentially result in unique toxicities. Cutaneous adverse events (CAE) after sequential exposure to these agents represents one toxicity that needs further description. Methods After retrospectively reviewing charts of patients from 2015 to 2018, we identified six patients who experienced CAEs after recent exposure to sequential immunotherapy and TT or vice versa for the treatment for metastatic melanoma at the University of North Carolina, Chapel Hill. Skin biopsies were available in five patients. Results Five patients received TT after immunotherapy, and one patient received immunotherapy after TT. TT consisted of vemurafenib/cobimetinib (V/C) in five patients with four patients starting V/C immediately before manifesting with a CAE. In patients receiving V/C after immunotherapy, the median time from beginning V/C to development of CAE was 14.5 days. The clinical presentation of diffuse morbilliform rash, fevers, hypotension, and end-organ damage raised concern for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome. Histopathological features of lympho-eosinophilic infiltrate were supportive of a drug eruption. Immunotherapy or TT were re-initiated in five patients within 1–8 weeks after resolution of the index CAE. This resulted in two patients re-experiencing the CAE. Both of these patients were off prednisone at the time of therapy re-initiation, whereas none of the patients who were restarted on targeted therapy with a steroid overlap had a rash recurrence. Conclusions Sequential treatment using immunotherapy and TT, especially the sequence of V/C after immunotherapy appears to be the most common trigger for CAE with a median time to onset of approximately 2 weeks. Although the clinical presentation of these CAEs can be dramatic, they respond well to prednisone therapy. This unique presentation suggests that it may be reasonably safe to re-challenge certain patients with a steroid overlap after rash resolution.
    URI
    http://hdl.handle.net/10342/8067
    Subject
    Cutaneous adverse events, Metastatic melanoma, B-RAF inhibitors, Immune checkpoint blockade, Vemurafenib/cobimetinib, DRESS syndrome
    Date
    2018-12-16
    Citation:
    APA:
    Naqash, Abdul Rafeh, & File, Danielle M., & Ziemer, Carolyn M., & Whang, Young E., & Landman, Paula, & Googe, Paul B., & Collichio, Frances A.. (December 2018). Cutaneous adverse reactions in B-RAF positive metastatic melanoma following sequential treatment with B-RAF/MEK inhibitors and immune checkpoint blockade or vice versa. A single-institutional case-series. Journal for Immunotherapy of Cancer, (7:4), p.. Retrieved from http://hdl.handle.net/10342/8067

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    MLA:
    Naqash, Abdul Rafeh, and File, Danielle M., and Ziemer, Carolyn M., and Whang, Young E., and Landman, Paula, and Googe, Paul B., and Collichio, Frances A.. "Cutaneous adverse reactions in B-RAF positive metastatic melanoma following sequential treatment with B-RAF/MEK inhibitors and immune checkpoint blockade or vice versa. A single-institutional case-series". Journal for Immunotherapy of Cancer. 7:4. (.), December 2018. April 20, 2021. http://hdl.handle.net/10342/8067.
    Chicago:
    Naqash, Abdul Rafeh and File, Danielle M. and Ziemer, Carolyn M. and Whang, Young E. and Landman, Paula and Googe, Paul B. and Collichio, Frances A., "Cutaneous adverse reactions in B-RAF positive metastatic melanoma following sequential treatment with B-RAF/MEK inhibitors and immune checkpoint blockade or vice versa. A single-institutional case-series," Journal for Immunotherapy of Cancer 7, no. 4 (December 2018), http://hdl.handle.net/10342/8067 (accessed April 20, 2021).
    AMA:
    Naqash, Abdul Rafeh, File, Danielle M., Ziemer, Carolyn M., Whang, Young E., Landman, Paula, Googe, Paul B., Collichio, Frances A.. Cutaneous adverse reactions in B-RAF positive metastatic melanoma following sequential treatment with B-RAF/MEK inhibitors and immune checkpoint blockade or vice versa. A single-institutional case-series. Journal for Immunotherapy of Cancer. December 2018; 7(4) . http://hdl.handle.net/10342/8067. Accessed April 20, 2021.
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