Wennberg et al

Title: Photodynamic Therapy with Methyl Aminolevulinate for Prevention of New Skin Lesions in Transplant Recipients: a Randomized Study

Author: Wennberg A-M, Stenquist B, Stockfleth E, Keohane S, Lear JT, Jemec G, et al.

Reference: Transplantation 2008;86(3):423-9 (by clicking on this link you will be leaving this site - Galderma is not responsible for the content)

Key statements:

  • Treatment with methyl aminolevulinate photodynamic therapy (MAL-PDT) was effective in preventing new actinic keratosis (AK) lesions in organ transplant recipients under immunosuppressive therapy. At 3 months, there was a reduction of 46% (p=0.006) with MAL-PDT vs. routine treatment (mainly cryotherapy) and a greater reduction in patients having undergone organ transplantation within 10 years (61%). At 27 months the occurrence of new lesions was still visible but no longer significant between the two treatments (p=0.13).
  • AK lesion complete response at 3 months and accumulated recurrence rates at 27 months were similar in both treatments.
  • MAL-PDT gives a favorable cosmetic outcome and causes less scarring and tissue destruction than cryosurgery and surgery. At 27 months, hypopigmentation was reported for 16% vs. 51% of patients and scars for 13% vs. 24% of patients, respectively.
  • Adverse events (AEs) with MAL-PDT were consistent with the tolerability profile of this treatment modality. 75% of patients reported AEs, mainly local and transient (predominantly pain) vs. 51% for the control area.

Objectives: to evaluate the efficacy and tolerability of regularly repeated field Metvix® during 15 months as a preventive treatment for premalignant skin lesions in organ transplant recipients receiving long-term immunosuppressive therapy.

Design: an open, randomized, intrapatient multicenter study was conducted in 11 hospital dermatology outpatient centers in Europe.

Patients were organ transplant recipients who had received immunosuppressive therapy for more than 3 years and had skin lesions (>85% AKs - at least 2 and up to 10 AK lesions, but also basal cell carcinoma [BCC], squamous cell carcinoma [SCC] in situ and/or warts) in each of two symmetrical 50 cm2 contralateral areas on the face, scalp, neck, trunk or extremities; one area was treated with MAL-PDT (77% of per protocol (PP) population received 5 treatments within 15 months) and the other area at the investigator's choice (cryotherapy for 83% of treatments; 5-fluoro and imiquimod were not used).

Evaluation was carried out 3, 9, 15, 21 and 27 months after initial treatment, in terms of:

  • Response to treatment (complete, partial, no response).
  • Cosmetic outcome assessed by the investigator and patient as none, slight or obvious.
  • AEs, rated as mild, moderate or severe.

Cumulative 27 month recurrence rate was also reported.

Key Results: PP - 75 patients with 433 lesions in the treatment area and 377 lesions in the control area.

Efficacy:

  • Occurrence of new lesions:
    At 3 months, there were significantly fewer new AK lesions in the treatment area (43 vs. 80). However, at 27 months there was no statistical difference (253 vs. 312).
  • At 3 months, there was a better response to field Metvix® for patients having undergone organ transplantation within 10 years (61% vs. 42%). This difference was not observed at 27 months (29% vs. 22%).
  • Lesion complete response and recurrence:
    AK lesion complete response at 3 months and recurrence rates during follow-up were similar in both treatment and control areas. Complete response at 3 months was 77% for the treatment area vs. 74% for the control area.
  • Cosmetic outcome:
    At 27 months, hypopigmentation was reported in the treatment area in 16% of patients vs. 51% for the control area, whereas scar formation was observed in 13% vs. 24% of patients, respectively.
  • Adverse events:
    75% of patients reported AEs associated with Metvix®, most of which were transient, vs. 48% in the control area.

Other Key Points:

  • An increased tolerance of pain was observed with repeated Metvix® sessions.
  • Metvix® can be repeated shortly if required and does not complicate surgery in the future, which makes it an attractive modality for the transplant population where continuous care of skin lesions is needed.

Conclusion: regular field therapy with Metvix® PDT has potential for preventing AK lesions in organ transplant recipients. The authors state that their conclusions are preliminary and warrant further investigation.