Impressive Continuous Complete Response after Mogamulizumab in a Heavily Pretreated Sézary Syndrome Patient
Received: April 29, 2020
Accepted: June 8, 2020
Mediterr J Hematol Infect Dis 2020, 12(1): e2020040 DOI 10.4084/MJHID.2020.040
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Sézary syndrome (SS) is a rare lymphoproliferative neoplasm, almost
incurable outside the setting of allogeneic transplantable patients.
The prognosis for relapsed/refractory patients remains poor, as the
available drugs confer short-lasting remission. In this setting, the
anti-chemokine receptor type 4 (CCR4) monoclonal antibody mogamulizumab
demonstrated efficacy in an international, open-label, randomized
controlled phase 3 trial (MAVORIC) versus vorinostat.
|Figure 1. Patient before starting treatment (A, back; B, legs).|
Our patient obtained an impressively rapid improvement of symptoms already from the third cycle, while a partial response (PR) was achieved after the fifth cycle. A complete response (CR) was documented after the 10th cycle (Figures 2A and 2B). Therapy was well tolerated and went on without complications until the 27th cycle when the patient developed a plaque skin lesion in the zygomatic area (without pruritus). In the suspect of disease relapse, a punch-cutaneous biopsy was performed in September 2017 and then again in October 2017 for the persistence of this lesion. Results of both biopsies were consistent with a drug-related lesion, with no signs of active disease. Our patient received 30 cycles of mogamulizumab overall, then we decided to discontinue her from the treatment protocol in October 2017, due to the persistence of this lesion compatible with persistent grade 2 drug toxicity, histologically documented.
|Figure 2. Patient after achieving a complete response (A, back; B, legs).|
After mogamulizumab discontinuation, this patient was admitted to the follow-up phase. The cutaneous zygomatic lesion quickly disappeared, and no further lesions appeared after that. At the latest available follow-up, 2.5 years after therapy discontinuation, she is still in CR without having undergone further therapy after mogamulizumab.
The patient gave written, informed consent to publish her data and images.
Our patient demonstrates that, in line with the data coming from MAVORIC, mogamulizumab can induce good responses. These responses include few CRs, also if very rare (only 5 out of 186 patients in MAVORIC), and the time to achieve a response is quite short also in heavily pretreated patients. In our case, a clinical response was achieved after the third cycle, and a PR was documented after the fifth one, in line with the median time to mogamulizumab response of 3.3 months. Another observation that our case suggests is that that this drug can induce skin lesions to distinguish from those of the relapsing disease. Unfortunately, we have no more tissue slides to perform the research of T-regs depletion in our patient, nor the CCR4 mutational status. Analysis of T-regs depletion and mutational status could be a very stimulating starting point to perform new studies and to deepen knowledge about the properties of mogamulizumab in patients who are going to receive it in the future. Skin toxicity was durable and led to treatment discontinuation in our patient, but this case report also showed that this adverse event was reversible and did not invalidate the response. To our knowledge, there is not an update about MAVORIC after its publication in 2018; thus, we do not know if our patient is the only one who achieved this extraordinary long-lasting response, or if also other patients did. All the other patients enrolled in the MAVORIC study at our Institution progressed and required subsequent therapy.
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