WAIKOLOA, HAWAII – The topical immunomodulator imiquimod appears to be beneficial therapy in selected patients with lentigo maligna or lentigo maligna melanoma, according to the largest case series to date.
"Based upon our experience, imiquimod 5% cream is a viable option as primary or adjunctive therapy of lentigo maligna and the in situ component of lentigo maligna melanoma in patients where surgery is really not feasible, or you’ve optimized surgical margins without achieving a clear histologic margin. I emphasize this should only be considered for in situ melanoma; we’re not using it to treat invasive melanoma," Dr. Susan M. Swetter said at the Hawaii Dermatology Seminar sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.
Dr. Susan Swetter
A cautionary note: Imiquimod (Aldara) for lentigo maligna (LM) is off-label therapy. It’s crucial to discuss with candidates the limitations of nonsurgical treatment for LM and lentigo maligna melanoma (LMM), which includes increased risk of local recurrence because of the lack of margin control, the possibility of a missed invasive melanoma, and the lack of supporting evidence from randomized trials with long-term follow-up.
"When we’re talking about imiquimod as potential treatment for lentigo maligna – and I can’t emphasize this enough – it requires close clinical follow-up, [carefully] documented discussion with the patient, and strong patient compliance. We have had cases of lentigo maligna melanoma where there have been metastases, not because of the in situ component, but because of the initial invasive tumor. You’ve got to follow these patients long term like a hawk. I follow them with Wood’s lamp and dermoscopy, and I biopsy any pigmentation," said Dr. Swetter, professor of dermatology and director of the pigmented lesion and cutaneous melanoma clinic at Stanford (Calif.) University Medical Center.
That being said, there are many scenarios in which surgical excision – the recommended first-line treatment for LM and LMM – might not be feasible. These include the sizable numbers of patients of advanced age who have limiting comorbid medical conditions or cognitive impairment. Also, LM has a strong predilection for the head and neck, and some affected patients avidly wish to avoid potentially disfiguring surgery.
Dr. Swetter presented a retrospective study of 60 patients with 62 LM or LMM lesions treated with imiquimod 5% cream at Stanford or the Veterans Affairs Palo Alto Health Care System. Most she treated personally. Imiquimod was primary therapy in 20 cases and adjuvant therapy following failed surgical attempts to achieve histologic clearance in the rest.
Pathologically, 45% of the lesions were LM, 29% were atypical intraepidermal melanocytic proliferations or poorly evolving LM, and 26% were LMM with histologic transection of LM and excision of the invasive melanoma component. Three-quarters of treated lesions were on the head or neck.
The lesions had a mean Breslow depth of 1.17 mm. Prior to imiquimod, half of the patients had one excision and another 19% had two or more. The mean duration of imiquimod therapy was 10.9 weeks, with a mean post treatment follow-up of 38 months.
"I typically treat to a 2-cm margin around the lesion," the dermatologist noted.
The overall clinical or histologic clearance rate was 86%. This is strikingly similar to the collective 82% rate in 46 reports involving 264 treated patients described in a published review by dermatologists at the University of Colorado, Denver (Dermatol. Surg. 2012;38:937-46).
An inflammatory response to imiquimod was predictive of favorable treatment outcome, especially in patients using the topical agent as primary therapy. Of the 20 patients who used imiquimod as primary therapy, all 16 who experienced clinical and/or histologic clearance had an initial inflammatory response. In contrast, none of the four clinical nonresponders showed an inflammatory response.
Outcomes weren’t quite as good in patients using imiquimod as adjuvant therapy.
"This is likely related to more challenging cases in the adjuvant setting, where the patients may have failed multiple attempts at wide local excision for histologic clearance," Dr. Swetter surmised.
Although the use of imiquimod as treatment for LM remains off label, it’s worth noting that it receives support in major practice guidelines. National Comprehensive Cancer Network guidelines recommend consideration of topical imiquimod or radiotherapy as adjunctive treatment for LM in selected patients after optimal surgery, with a level 2B recommendation. And the American Academy of Dermatology lists imiquimod as among the adjunctive options (J. Am. Acad. Dermatol. 2009; 61:865-7). What’s really needed now, according to Dr. Swetter, is a randomized controlled trial to firmly demonstrate benefit.
Dr. Allan Halpern
Session chair Dr. Allan C. Halpern said he and his colleagues have also been using topical imiquimod to treat LM with impressive results.