diffuse large B-cell lymphoma
Credit: Leszek Woźniak
& Krzysztof W. Zieliński
An immunotherapeutic agent can confer clinical benefit in patients with relapsed cutaneous B-cell lymphoma (CBCL), results of a small phase 2 study suggest.
The therapy, TG1042, is human adenovirus type 5 engineered to express interferon-gamma.
Repeat injections of TG1042 elicited responses in 11 of 12 evaluable patients, with complete responses in 7.
All 13 of the patients enrolled on the study experienced an adverse event that may have been related to TG1042, but most were grade 1 or 2 in severity.
“Intralesional TG1042 therapy is well-tolerated and results in lasting tumor regressions,” said study author Reinhard Dummer, MD, of the University of Zurich in Switzerland.
He and his colleagues reported these results in PLOS ONE. The study was sponsored by Transgene SA, makers of TG1042.
The trial consisted of 13 patients with primary CBCL, including primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle center B-cell lymphoma, primary cutaneous diffuse large B-cell lymphoma other than leg type, and T-cell/histiocyte-rich B-cell lymphoma.
Patients were required to have either relapsed or active disease after at least 1 first-line treatment.
The patients received intralesional injections of TG1042 at 5 x 1010 viral particles per lesion. They could receive injections in up to 6 lesions, which were treated simultaneously on days 1, 8, and 15 of a 4-week cycle.
Patients did not receive treatment during the fourth week. At the end of the cycle, the researchers evaluated tumors for response.
If patients’ disease did not progress, they could receive an additional cycle, up to a maximum of 4. If patients responded to treatment and their lesions disappeared, they were eligible to receive a second series of injections in untreated lesions.
Of the 13 patients treated, 12 were evaluable for response. Eleven of the patients (85%) achieved an objective response—7 complete responses and 4 partial responses. One patient had stable disease.
All reviewed skin biopsies showed that lesions improved after treatment, with a decrease of the lymphoid infiltrate.
The median time to first objective response was 3.2 months (rage, 1-17.5 months). Among complete responders, the median time to response was 4.3 months (range, 1.4-17.5 months).
The median time to progression was 23.5 months (range, 6.5-26.4+ months).
All 13 patients were included in the safety evaluation, and all experienced 1 or more adverse events that were considered possibly or probably related to the treatment.
One patient discontinued treatment due to influenza-like illness, pyrexia, headache, and skin blisters that were possibly related to TG1042.
Another patient had grade 3 increased lipase, but this was thought to be unrelated to TG1042. And it resolved without treatment.
All other adverse events were grade 1 or 2 in nature. They included fatigue, headache, pyrexia, chills, influenza-like illness, injection site irritation, injection site erythema, and injection site pain.
All of these reactions resolved after treatment discontinuation.
