Targeted Therapy for Cutaneous Lymphomas
The treatment of cutaneous lymphomas is a rapidly developing field of dermato-oncology. Newer targeted agents continue to be developed, with the future promising better treatments for advanced cutaneous lymphomas and with fewer adverse effects experienced.
By Dr Tee Shang Ian, National Skin Centre, Hon. Treasurer, 25th WCD
Targeted Therapy for Cutaneous Lymphomas Dr Tee Shang Ian, National Skin Centre, Hon. Treasurer, 25th WCD
The treatment of cutaneous lymphomas is a rapidly developing field of dermato-oncology. This is notable in the case of mycosis fungoides (MF) / Sezary syndrome (SS), which comprise the most common cutaneous lymphomas. Therapy for this condition remains stage-based, and skin-directed treatment such as topical steroids or retinoids, phototherapy or localised radiotherapy are recommended. In more advanced stages, systemic options such as bexarotene, interferon, single or multi-agent chemotherapy or haematopoietic stem-cell transplantation play a role. The advent of immunotherapy and targeted therapeutics has led to further advancements in treatment. These work by exploiting key pathways in tumour survival and proliferation. Brentuximab, an anti-CD30 antibody, shows good efficacy against relapsed or refractory CD30+ MF. This was demonstrated in the ALCANZA trial (open label RCT), which showed significant improvement in objective response lasting at least 4 months with brentuximab versus physician’s choice of methotrexate or bexarotene. Sub-group analysis showed improvement was not associated with large-cell transformation status. Mogamulizumab is an anti-CCR4 antibody used in MF/SS with blood involvement. Efficacy was demonstrated in the MAVORIC trial, an international open-label RCT, in which Mogamulizumab showed prolonged progression-free survival compared to vorinostat. Alemtuzumab (anti-CD52) appears effective in erythrodermic MF. A recent systematic review found that this was more effective in treating SS compared to
chemotherapy agents, also better overall response rate than for MF. Pembrolizumab (anti-PD-1) and vorinostat, romidepsin (HDAC inhibitors) have been evaluated in phase II trials, all of which showed promising results for their use.
Of the non-MF/SS cutaneous T-cell lymphomas, brentuximab is unsurprisingly effective in the treatment of CD30+ lymphoproliferative disorders (lymphomatoid papulosis and cutaneous anaplastic large cell lymphoma). Case reports of utility of brentuximab in refractory / relapsed primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma may also be found. Trials of targeted therapies are ongoing in adult T-cell leukemia / lymphoma (mogamulizumab and lenalidomide) and peripheral T-cell lymphoma, NOS and angioimmunoblastic T-cell lymphoma (romidepsin, brentuximab, alemtuzumab). Finally, rituximab has been used in patient with primary cutaneous B-cell lymphoma, especially those with disseminated lesions or lesions in difficult locations. Newer targeted agents continue to be developed, with the future promising better treatments for advanced cutaneous lymphomas and with fewer adverse effects experienced.
The Dermatological Society of Singapore (DSS) held their 33rd Annual Scientific Meeting virtually on 24-25th July 2021. The theme for the meeting was ‘The Era of Targeted Therapy in Dermatology’.
DSS is the host organization of the World Congress Dermatology in Singapore 2023.