LOS ANGELES Two rare types of non-Hodgkin's lymphomas responded to treatment with intratumoral injections of an investigational immunomodulator plus radiotherapy in a pilot study of seven patients, Dr. Anjali V. Morales reported at the annual meeting of the Society for Investigative Dermatology.
Six patients with mycosis fungoides and one patient with primary cutaneous B-cell lymphoma (CBCL) underwent low-dose radiotherapy to a single tumor site on day 1 and 2 plus injections of CpG 7909 to the same tumor within 24 hours before and after the radiotherapy. This treatment regimen was repeated weekly for a total of nine sessions. Noninjected tumors were monitored to assess systemic effects of the treatment.
CpG 7909 is an agonist to the protein TLR 9 (toll-like receptor 9) and belongs to a new class of immunomodulators that activate B cells and plasmacytoid dendritic cells. It showed promise as monotherapy for cutaneous T-cell lymphoma in a previous trial, said Dr. Morales of Stanford (Calif.) University.
In the current study, the combination of CpG 7909 and low-dose radiotherapy produced partial responses in two patients with mycosis fungoides and the one patient with CBCL. Another patient with mycosis fungoides showed a minor response, and the other three patients had stable disease, she reported.
A partial response was defined as greater than a 50% reduction in tumor volume or severity-weighted assessment tool (SWAT) score, compared with baseline. A minor response was defined as a 25%-50% reduction in tumor volume or SWAT score, compared with baseline.
The responses appeared after 6-9 weeks in patients with mycosis fungoides and after 4 weeks in the patient with CBCL. "We did note that responses were short-lived," so the protocol has been amended to enhance the systemic antitumor response, Dr. Morales said.
The investigators are enrolling patients now in a study that will administer low-dose radiotherapy and CpG 7909 injections to one tumor site on day 1 and 2, followed by two weekly CpG 7909 injections. At week 4, a second tumor site will be treated with radiotherapy and injections, followed by four weekly injections of CpG 7909. Nontreated lesions will be assessed for response.
The treatment appeared to be well tolerated, with grade 1-2 adverse events in all patients, she said. These included erythema, pain, and induration at the injection sites plus fever and fatigue in all patients. Six patients reported myalgia and arthralgia, three complained of headache, and one had nausea.
Researchers have theorized that intratumoral injection of CpG 7909 activates dendritic cells, which migrate to lymph nodes and promote a systemic antitumor immune response.
The study was initiated by Stanford faculty and funded by the National Institutes of Health, Dr. Morales said.