By Shira Klapper, Senior Writer/Editor

For most patients with peripheral T-cell lymphoma (PTCL), long-term progression-free survival (PFS) is an elusive goal. And for patients with this aggressive form of lymphoma who relapse—or who never respond to standard first-line chemotherapies such as CHOP and EPOCH to begin with—outcomes are usually poor.

	Michinori Ogura, MD, PhD

“Patients are waiting for the development of new effective drugs since there is still an unmet need in the treatment of relapsed or refractory patients with PTCL and cutaneous T-cell lymphoma (CTCL),” said Michinori Ogura, MD, PhD, the first author of a study in the Journal of Clinical Oncology (JCO) online ahead of print (March 10th, 2014) that looked at the effects of the anti-CCR4 antibody, mogamulizumab, on patients with PTCL and CTCL. PTCL and CTCL are two major subtypes of peripheral Natural killer (NK)/T-cell neoplasms. 

The study, “Multicenter Phase II Study of Mogamulizumab (KW-0761), a Defucosylated Anti-CCR4 Antibody, in Patients with Relapsed Peripheral T-Cell Lymphoma and Cutaneous T-cell Lymphoma,” was carried out across multiple sites in Japan.

Mogamulizumab is a monoclonal antibody that targets the CC chemokine 4 receptor (CCR4), a protein that is associated with tumor growth and metastasis. The term, “defucosylated,” refers to the fact that fucose sugars have been detached from the antibody, a process which enhances the antibody-dependent cellular cytotoxicity (ADCC) of therapeutic antibodies. Mogamulizumab is approved in Japan as a treatment for relapsed or refractory adult T-cell leukemia-lymphoma, a subtype of PTCL that is retrovirus-associated.

This current study comes on the heels of a previous 2010 mogamulizumab study from Japan, a country in which peripheral NK/T-cell neoplasms account for 25% of all non-Hodgkin lymphomas (NHLs); in Western countries, by comparison, peripheral NK/T-cell neoplasms account for 10% of all NHL’s. In the previous phase I study, one out of the three patients with relapsed PTCL/CTCL who underwent treatment with mogamulizumab had a partial response (PR). In addition, a 2011 phase II study in the U.S. found that patients with relapsed or refractory CTCL treated with the antibody had an overall response rate (ORR) of 37% and a median PFS of 341 days.

For the current JCO study, the research team recruited 37 patients with PTCL or CTCL who were CCR4 positive. Mogamulizumab was administered once per week for eight weeks in order to assess the following endpoints: ORR, safety, PFS, and overall survival (OS).

The findings? While nine patients (24%) discontinued treatment due to progressive disease (PD) and three patients (8%) discontinued due to serious adverse events (SAEs), the ORR for the patients was 35%, with 14% achieving complete response (CR). The median PFS was 3.0 months; the median OS was not calculated. When the data were separated out according to lymphoma subtype, differences emerged: for those with PTCL, ORR was 34%, for those with CTCL, ORR was 38%.  By comparison, among the FDA-approved chemotherapy treatments for relapsed or refractory PTCL/CTCL, ORRs range from 25% to 34%.

On the safety front, many patients did experience grade 3 or 4 hematologic and dermatologic adverse events while undergoing treatment with mogamulizumab, but importantly, none of the toxicities led to death and all showed improvement over time.

“The toxicity profile of mogamulizumab is acceptable for patient populations because most of the drug-related adverse events were manageable and reversible,” said Dr. Ogura.

Dr. Ogura noted that while further studies are needed to assess mogamulizumab—both in the lab and in clinical settings—the results of the study are promising.

“Mogamulizumab would be expected to provide a novel treatment option in patients with CCR4-positive relapsed PTCL/CTCL.”

Michinori Ogura, MD, PhD, is a Visiting Professor in the Department of Medicine at the Fujita Health University, Toyoake, and an Advisor in the Clinical Trial Center, Nagoya Daini Red Cross Hospital, Nagoya, Japan. He is a core member of the Lymphoma Study Group of Japan Clinical Oncology Group and a Chairman of the Hematological Malignancy Study Group in Japan. Dr. Ogura has been as ASCO member since 2012.

Source

Click here to read the abstract.
 

Click here to view a PDF of the full article.

Ogura, M, Ishida, T, Hatake, K, et al. Multicenter phase II study of mogamulizumab (kw-0761), a defucosylated anti-ccr4 antibody, in patients with relapsed peripheral t-cell lymphoma and cutaneous t-cell lymphoma. J Clin Oncol. 2014; Published online ahead of print 3.10.2014.

The Exclusive Coverage series on ASCO.org highlights selected research from JCO with additional perspective provided by the lead or corresponding author.

@ 2014 American Society of Clinical Oncology