Mogamulizumab Demonstrates Antitumor Activity in Adult T-Cell Leukemia/Lymphoma

Nearly two-thirds of patients with adult T-cell leukemia-lymphoma (ATLL) responded to treatment with mogamulizumab as a single agent or as part of a treatment combination, according to results from a multicenter, prospective observational study published in Blood Advances. Patients’ immunologic status before treatment was significantly associated with outcome after mogamulizumab, the authors, led by Kentaro Yonekura, MD, PhD, from Imamura General Hospital in Kagoshima, Japan, noted.

Mogamulizumab is a monoclonal antibody directed against CC chemokine receptor 4 (CCR4), which is overexpressed in malignant T-cells, and is approved in Japan for the treatment of newly diagnosed and relapsed/refractory ATLL.

“[Treatment-related] adverse events (AEs), such as severe skin disorders or viral infection, have been found to be clinically problematic,” the authors explained. But, “quite puzzlingly, moderate skin-related AEs after mogamulizumab were associated with a favorable prognosis.”

A higher percentage of B cells might reflect an overall favorable immune status leading to a good outcome after mogamulizumab treatment.

Although these AEs are considered to be associated with the depletion of CCR4 cells, especially regulatory T cells, data on the detailed immune alterations resulting from mogamulizumab treatment are not yet available, they added. In this study, Dr. Yonekura and investigators evaluated mogamulizumab in 101 patients with ATLL, focusing on patients’ clinical and immunological parameters before mogamulizumab and on their relationships with treatment outcome.

Participants’ median age was 69 years (range = 36-86). Acute ATLL was the most common diagnosis (n=68), followed by lymphoma (n=18), unfavorable chronic (n=10), smoldering (n=3), and favorable chronic subtypes (n=2).

Seventeen patients had previously untreated disease, and the remaining 84 had previously received systemic chemotherapy.

After enrollment, 32 received mogamulizumab monotherapy and 69 received mogamulizumab-containing combination therapies (such as a mogamulizumab plus modified LSG15 regimen of vincristine, cyclophosphamide, doxorubicin, and prednisolone).

Overall, patients received a mean of 6 mogamulizumab infusions (1 mg/kg).

Of the 101 patients treated with mogamulizumab, 66 had a response, for an overall response rate of 65%. This included 44 complete responses, the authors reported. Nonresponders had either stable disease (n=7) or progressive disease (n=28).

Median progression-free survival and overall survival (OS) were 7.4 months and 16.0 months, respectively.

In multivariate analysis, there was no significant influence of patient sex, age, or previous treatment status on OS. However, having an acute or lymphoma disease subtype and higher serum soluble interleukin-2 receptor (sIL-2R) level did influence survival (TABLE). There also was no significant difference in OS between patients treated with mogamulizumab as monotherapy or as part of combination therapy (median OS = 30.9 vs. 12.8 months; p=0.156).

When the investigators looked at patients’ immunological parameters, they found that immunologic status before mogamulizumab treatment, as reflected by the percentage of B cells in peripheral blood mononuclear cells and the magnitude of the human T-cell lymphotropic virus type 1 Tax-specific T-cell immune response, was significantly associated with the outcome of treatment with mogamulizumab.

For example, those with a higher percentage of Tax-specific cytotoxic T lymphocytes (CTLs) within lymphocytes (i.e., >0.002%) had significantly longer OS than those with fewer Tax-specific CTLs (median = 19.6 vs. 11.3 months; p=0.028).

“Now, we can confidently propose that a higher percentage of B cells might reflect an overall favorable immune status leading to a good outcome after mogamulizumab treatment,” the researchers wrote. They added that regulatory T cell phenotype did not significantly affect patients’ prognosis.

“On the basis of the present study focusing on the patients’ immunologic status before mogamulizumab and its influence on outcome, further time series analysis, in addition to comprehensive genomic analyses, is warranted to establish predictive markers for treatment success and to better understand the mechanisms of action of mogamulizumab,” the authors concluded.

However, they noted that the study findings are limited by the inclusion of previously untreated and treated patients, which could affect participants’ immunologic status before mogamulizumab. The variety of treatment regimens that patients received could also affect the clinical and immunologic outcomes observed in this study.

Study authors report relationships with Kyowa Kirin, the manufacturer of mogamulizumab.

Reference

Yonekura K, Kusumoto S, Choi I, et al. Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study. Blood Adv. 2020;4(20):5133-5145.