Dose‐intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T‐cell leukaemia‐lymphoma: a randomized phase II study

Abstract

SummaryThis multicentre, randomized, phase II study was conducted to examine whether the addition of mogamulizumab, a humanized anti‐CC chemokine receptor 4 antibody, to mLSG15, a dose‐intensified chemotherapy, further increases efficacy without compromising safety of patients with newly diagnosed aggressive adult T‐cell leukaemia‐lymphoma (ATL). Patients were assigned 1:1 to receive mLSG15 plus mogamulizumab or mLSG15 alone. The primary endpoint was the complete response rate (%CR); secondary endpoints included the overall response rate (ORR) and safety. The %CR and ORR in the mLSG15‐plus‐mogamulizumab arm (n = 29) were 52% [95% confidence interval (CI), 33–71%] and 86%, respectively; the corresponding values in the mLSG15 arm (n = 24) were 33% (95% CI, 16–55%) and 75%, respectively. Grade ≥ 3 treatment‐emergent adverse events, including anaemia, thrombocytopenia, lymphopenia, leucopenia and decreased appetite, were observed more frequently (≥10% difference) in the mLSG15‐plus‐mogamulizumab arm. Several adverse events, including skin disorders, cytomegalovirus infection, pyrexia, hyperglycaemia and interstitial lung disease, were observed only in the mLSG15‐plus‐mogamulizumab arm. Although the combination strategy showed a potentially less favourable safety profile, a higher %CR was achieved, providing the basis for further investigation of this novel treatment for newly diagnosed aggressive ATL. This study was registered at ClinicalTrials.gov, identifier: NCT01173887.

Cytomegalovirus Pneumonia after Anti-CC-chemokine Receptor 4 Monoclonal Antibody (Mogamulizumab) Therapy in an Angioimmunoblastic T-cell Lymphoma Patient

“…One patient died because of CMV encephalitis. Furthermore, Ishida et al reported that 4 patients (14%) who received mLSG15 combined with mogamulizumab developed CMV infection, which was not observed in the patients who received mLSG15 therapy alone (12). This report suggested that the addition of mogamulizumab to systemic therapy might further increase the incidence of CMV infection.…”

Cutaneous lymphomas: A review

“…Treatment is based on clinical signs, with skin-directed therapy or interferon associated with zidovudine in indolent cases and with systemic multidrug therapy or bone marrow transplantation in aggressive cases 1,18 . Phase 2 clinical trials with the anti-CCR4 monoclonal antibody mogamulizulab are currently being conducted, and these show promising responses thus far in refractory and aggressive cases ATLL 90 .…”

The Impact of a Humanized CCR4 Antibody (Mogamulizumab) on Patients with Aggressive-Type Adult T-Cell Leukemia-Lymphoma Treated with Allogeneic Hematopoietic Stem Cell Transplantation

“…17 Mogamulizumab, a humanized CCR4 antibody, is a newly developed antibody that is effective for refractory and relapsed ATL, and newly diagnosed ATL. [18][19][20][21] It provided a breakthrough paradigm shift to a molecule-targeted approach for ATL therapy. [18][19][20][21] Mogamulizumab attacks targeted ATL cells via antibody-dependent cellular cytotoxicity and natural killer cells.…”