Hypersensitivity in ALK-positive lung cancers exposed to ALK inhibitors: a case of successful switch to an alternative ALK inhibitor and systematic review of the literature

Deng, Lei; Sharma, Janaki; Ravera, Elizabeth; Halmos, Balázs; Cheng, Haiying

doi:10.2147/lctt.s173948

Cited by 3 publications

(3 citation statements)

References 15 publications

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“…ALK inhibitors are associated with immediate and delayed‐type hypersensitivity reactions 9 . Various cutaneous adverse reactions can occur, including urticaria, morbilliform, and acneiform eruptions, photosensitivity reactions, erythema multiforme, and toxic epidermal necrolysis 10‐14 . However, a sarcoidal drug reaction involving the skin, to our knowledge, has not been previously reported.…”

Section: Discussionmentioning

confidence: 97%

Cutaneous sarcoid‐like drug reaction caused by an anaplastic lymphoma kinase inhibitor

et al. 2020

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Anaplastic lymphoma kinase (ALK) rearranged lung cancers represent 4% to 6% of all pulmonary adenocarcinomas, and echinoderm microtubule associated protein like 4 (EML4)‐ALK fusions are the most common subgroup. Herein, we report a case of two successive drug reactions due to ALK inhibitors. A 69‐year‐old female with stage IVB EML4‐ALK fused lung adenocarcinoma developed a generalized morbilliform eruption 10 days after starting alectinib. Skin biopsy findings were consistent with a drug reaction. Her findings resolved after alectinib was discontinued. Another ALK inhibitor, lorlatinib was started and she developed multiple asymptomatic cutaneous and oral nodules 4 months later. Biopsies from these nodules showed sarcoidal granulomas without evidence of metastases or infection. ALK inhibitors are associated with numerous adverse events, including various cutaneous eruptions. However, a sarcoidal drug reaction involving the skin has not been reported. Identification of drug reactions to targeted therapy can avoid long‐term sequelae and misinterpretation of the clinical findings as disease progression or infection.

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Section: Discussionmentioning

confidence: 97%

Cutaneous sarcoid‐like drug reaction caused by an anaplastic lymphoma kinase inhibitor

et al. 2020

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“…As aforementioned, Brigatinib was then chosen due to its differing chemical structure. To corroborate likely success of switch there are at least two other cases of successful changes from Alectinib to Brigatinib due to serious dermatological reactions [ 19 , 20 ]. Unfortunately, understanding that relation will never be accomplished as a result of loss of contact with the patient following her move out of the country.…”

Section: Discussionmentioning

confidence: 99%

Alectinib-induced rash unresponsive to desensitization: a case report and literature review

Rodriguez,

Dindak,

Kline

et al. 2023

BMC Pulm Med

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Background Since the inception of targeted therapies in treating lung cancer, providers have had to be aware of a new host of side effects when selecting management options for patients. Although targeted therapies are creating increased hope for patients with non-small cell lung cancers (NSCLC), understanding their side effects presents a challenge for providers. Alectinib, a second-generation tyrosine kinase inhibitor, is a targeted therapy used in patients with non-small cell lung cancer found to have anaplastic lymphoma kinase (ALK) mutations. Alectinib is the focus of this case report and literature review as we seek to understand side effects providers may encounter when prescribing these therapies. Case presentation We begin our report with the case of a 63-year-old Hispanic female with stage IIIA non-small cell lung cancer found to have the ALK genomic alteration. She was started on Alectinib, and on Day 11, she developed a severe maculopapular rash requiring hospitalization. After complete resolution, desensitization with Alectinib was attempted but unsuccessful. Conclusions Despite the unsuccessful desensitization of this patient, it is important to report this rare side effect in order to better understand how providers can pursue management. Case reports such as this can aid providers in potentially preventing, treating, and rechallenging patients on targeted therapies in the future.

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“…Although the utility and risk/benefit ratio of desensitization are unclear, cross-reactive hypersensitivity reactions and adverse events of the other ALK TKIs also need to be taken into account when considering treatment options after the development of a grade 3 toxicity. 4 Alectinib specifically is preferred as first-line therapy in advanced ALK-positive NSCLC. After discussion with the patient and oncologist, the decision was made to pursue desensitization rather than switch to an alternative, second-line treatment.…”

Section: Discussionmentioning

confidence: 99%

Successful alectinib desensitization in a patient with anaplastic lymphoma kinase-positive adenocarcinoma of the lung and alectinib-induced drug rash

Anderson

Luczak

Ries

et al. 2020

J Oncol Pharm Pract

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Introduction Alectinib is an oral tyrosine kinase inhibitor currently recommended by the National Comprehensive Cancer Network (NCCN) as the preferred first-line treatment option for the treatment of metastatic anaplastic lymphoma kinase (ALK) gene rearrangement-positive non-small cell lung cancer (NSCLC). Skin toxicity is a known adverse effect of this medication, yet current recommendations are unclear regarding how to best manage patients who develop severe skin toxicity while taking alectinib. Case report Here, we describe a case of successful rechallenge with alectinib by utilizing a desensitization procedure in a patient who had developed severe alectinib-induced skin toxicity about two weeks into treatment. Management and outcome: Upon resolution of the initial skin toxicity symptoms, the patient was rechallenged with alectinib using a modified version of a previously published desensitization procedure. The patient tolerated the rechallenge with no recurrence of skin toxicity or other adverse effects and was able to continue treatment with alectinib. Discussion Alectinib is currently recommended as the preferred first-line treatment option for the treatment of metastatic anaplastic lymphoma kinase gene rearrangement-positive NSCLC due to improved progression-free survival when compared to crizotinib. The development of skin toxicity can lead to early discontinuation of alectinib treatment, forcing providers and patients to select alternative, potentially less effective options. This case report provides evidence that patients who have experienced severe skin toxicity due to alectinib may be able to continue this first-line treatment option by rechallenging them using a desensitization procedure.

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Hypersensitivity in ALK-positive lung cancers exposed to ALK inhibitors: a case of successful switch to an alternative ALK inhibitor and systematic review of the literature

Cited by 3 publications

References 15 publications

Cutaneous sarcoid‐like drug reaction caused by an anaplastic lymphoma kinase inhibitor

Cutaneous sarcoid‐like drug reaction caused by an anaplastic lymphoma kinase inhibitor

Alectinib-induced rash unresponsive to desensitization: a case report and literature review

Successful alectinib desensitization in a patient with anaplastic lymphoma kinase-positive adenocarcinoma of the lung and alectinib-induced drug rash

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