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

Abstract

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.

Patients with high-grade alectinib-induced skin rash: How do we desensitize these patients? A case report and review of literature

“…7,11 A literature review identified four cases (Table 2), of which three outlined their desensitization protocol. [7][8][9] In all four, the skin rash occurred 10-14 days of starting alectinib and did not reoccur after the desensitization protocol. There is no universal desensitization protocol.…”

“… 7 , 8 The restarting doses of alectinib in the other three cases were very low (20 mg, 37.5 mg and 40 mg), whereas we started at a higher dose of 150 mg twice daily. 7 – 9 Since alectinib comes in 150 mg capsules, we believe our starting dose was more convenient and feasible. Furthermore, considering that our patient had no prior allergies and experienced no additional complications except for a rash which completely resolved after stopping the medication, we felt it was reasonable to start at 150 mg twice daily with very close monitoring.…”

“…In the other three cases alectinib was titrated to 300 mg twice daily and 200 mg twice daily, 7 – 9 whereas we titrated to 600 mg twice daily. Although providers in the other two cases completed the desensitization protocol in a shorter period of time (8, 9 and 14 days compared to 23 days in our case), 7 – 9 we were able to reach a higher dose than their final dose by Day 3.…”

“…To our knowledge, only three case reports outlined desensitization protocols. 7 – 9 Here, we report a case of Grade 3 skin rash due to alectinib and our desensitization protocol.…”

Severe Skin Toxicity Caused by Sequential Anti-PD-1 Antibody and Alectinib in Non-small-cell Lung Cancer: A Report of Two Cases and a Literature Review

“…Severe skin rashes (Grade 3) because of alectinib treatment are rare events (0%-3%) (3,4). Table summarizes F: female, NSCLC: non-small cell lung cancer, EML4: echinoderm microtubule-associated protein-like4, ALK: anaplastic lymphoma kinase, KIF5: kinesin family member 5B, RET: rearranged during transfection, ICI; immune checkpoint inhibitor, HT1: hydroxytryptamine1, mPSL: methylprednisolone, PSL: prednisolone case reports of severe skin rash caused by alectinib (8)(9)(10)(11)(12). Erythema multiforme caused by alectinib was reported in one case by Kimura et al (8).…”