Treatment of a Delayed Hypersensitivity-like Reaction after Second-line Therapy with Dabrafenib-Trametinib: A Case Report

Rama Koneru^1, , Jahnavi Mundluru² and Abdul Subhan³

¹RS McLaughlin Durham Regional Cancer Center, Lakeridge Health, Oshawa, Canada

²Jagiellonian University Medical College, Krakow, Poland

³Poznan University of Medical Sciences, Poznan, Poland

Cite this paper:
Rama Koneru, Jahnavi Mundluru and Abdul Subhan. Treatment of a Delayed Hypersensitivity-like Reaction after Second-line Therapy with Dabrafenib-Trametinib: A Case Report. American Journal of Medical Case Reports. 2022; 10(5):140-145. doi: 10.12691/ajmcr-10-5-6

Abstract

Melanoma is the third most prevalent skin cancer with the highest mortality rate amongst skin cancers. Recent therapeutic developments have improved its treatment options, however significant toxicity can be a limiting factor. In this report, we describe a case of a rare, delayed hypersensitivity-like reaction after treatment with dabrafenib-trametinib as a second line therapy in a metastatic melanoma patient treated with pembrolizumab initially. A 62-year-old Caucasian male presented with a left axillary mass, which was found to be BRAF V600E positive malignant melanoma upon biopsy. He proceeded to have full axillary node dissection and was scheduled to receive adjuvant immunotherapy with pembrolizumab. However, the treatment was delayed by 3 weeks due to COVID-19. The patient developed subcutaneous metastases within that time. Although he was started on pembrolizumab, the metastases continued to progress. The patient then opted to begin dabrafenib-trametinib and was started on full dose therapy. After two weeks, there was significant reduction of metastases clinically. Two days after the follow-up, he presented to the emergency room with diffuse non-pruritic hives all over the body without any symptoms of angioedema. In addition, there was a sudden increase in size of the subcutaneous metastases. He was treated with 50 mg Benadryl and 50 mg prednisone with almost immediate resolution and discharged on prednisone. Dabrafenib-trametinib was temporarily discontinued. Due to the limited treatment options, the patient was carefully restarted on his dabrafenib-trametinib regimen with slow prednisone tapering. Patient has had an excellent response with complete resolution of his disease with no measurable lesions found on the latest CT scan. After a thorough literature search of OVID Medline + EMBASE, it was concluded that this is a rare presentation and only a few similar cases have been reported. Therefore, health care provider education and strategies for reintroduction of immunotherapy, as presented through a prednisone regimen in this case, is imperative for proper management of adverse events.

Keywords:
melanoma adverse events immunotherapy strategies PD-1 inhibitor BRAF/MEK inhibitor case report

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Miller AJ, Mihm MC. Melanoma. N Engl J Med. Massachusetts Medical Society; 2006; 355: 51-65.
[2]	Liu Y, Sheikh MS. Melanoma: Molecular Pathogenesis and Therapeutic Management. Mol Cell Pharmacol. 2014; 6: 228.
[3]	Cole BF, Gelber RD, Kirkwood JM, Goldhirsch A, Barylak E, Borden E. Quality-of-life-adjusted survival analysis of interferon alfa-2b adjuvant treatment of high-risk resected cutaneous melanoma: an Eastern Cooperative Oncology Group study. J Clin Oncol Off J Am Soc Clin Oncol. 1996; 14: 2666-73.
[4]	Sosman, Jeffrey A. Adjuvant and neoadjuvant therapy for cutaneous melanoma. UpToDate; 2021 [cited 2021 Jun 27]. Available from: http://n8t.cn/GbgEO.
[5]	Larkin J, Chiarion-Sileni V, Gonzalez R, Grob J-J, Rutkowski P, Lao CD, et al. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. Massachusetts Medical Society; 2019; 381: 1535-46.
[6]	Sosman, Jeffrey A. Overview of the management of advanced cutaneous melanoma. UpToDate [Internet]. 2021; Available from: http://n8t.cn/KqYQY.
[7]	Hauschild A, Dummer R, Schadendorf D, Santinami M, Atkinson V, Mandalà M, et al. Longer Follow-Up Confirms Relapse-Free Survival Benefit With Adjuvant Dabrafenib Plus Trametinib in Patients With Resected BRAF V600-Mutant Stage III Melanoma. J Clin Oncol Off J Am Soc Clin Oncol. 2018; 36: 3441-9.
[8]	Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, et al. Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med. Massachusetts Medical Society; 2018; 378: 1789-801.
[9]	Tarhini AA, Lee SJ, Hodi FS, Rao UNM, Cohen GI, Hamid O, et al. Phase III Study of Adjuvant Ipilimumab (3 or 10 mg/kg) Versus High-Dose Interferon Alfa-2b for Resected High-Risk Melanoma: North American Intergroup E1609. J Clin Oncol Off J Am Soc Clin Oncol. 2020; 38: 567-75.
[10]	Bar-Sela G, Abu-Amna M, Hadad S, Haim N, Shahar E. Successful desensitization protocol for hypersensitivity reaction probably caused by dabrafenib in a patient with metastatic melanoma. Jpn J Clin Oncol. 2015; 45: 881-3.
[11]	Tammaro A, Abruzzese C, Narcisi A, Cortesi G, Persechino F, Parisella FR, et al. Magnesium stearate: an underestimated allergen. J Biol Regul Homeost Agents. 2012; 26: 783-4.
[12]	Erfan G, Puig S, Carrera C, Arance A, Gaba L, Victoria I, et al. Development of Cutaneous Toxicities During Selective Anti-BRAF Therapies: Preventive Role of Combination with MEK Inhibitors. Acta Derm Venereol. 2017; 97: 258-60.
[13]	Pulluri B, Kumar A, Shaheen M, Jeter J, Sundararajan S. Tumor microenvironment changes leading to resistance of immune checkpoint inhibitors in metastatic melanoma and strategies to overcome resistance. Pharmacol Res. 2017; 123: 95-102.
[14]	Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer. 2012; 12: 237-51.
[15]	Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, et al. Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. Clin Cancer Res Off J Am Assoc Cancer Res. 2015; 21: 4286-93.
[16]	Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol Off J Am Soc Clin Oncol. 2010; 28: 3167-75.
[17]	Grogan N, Swami U, Bossler AD, Zakharia Y, Milhem M. Toxicities with targeted therapies after immunotherapy in metastatic melanoma. Melanoma Res. 2018; 28: 600-4.
[18]	Fujimura T, Kambayashi Y, Hidaka T, Tamabuchi E, Otake E, Tono H, et al. Severe erythema exudative multiforme developing from advanced melanoma treated with dabrafenib and trametinib followed by nivolumab. J Dermatol. 2018; 45: e35-6.
[19]	Shiohara T, Ushigome Y, Kano Y, Takahashi R. Crucial Role of Viral Reactivation in the Development of Severe Drug Eruptions: a Comprehensive Review. Clin Rev Allergy Immunol. 2015; 49: 192-202.