Some Complete Molecular Responses Seen With CML Vaccine

ATLANTA—Analysis of an early trial of a peptide vaccine, CMLVAX100, provides evidence of disease responses, including some complete molecular responses in patients with previously treated chronic myelogenous leukemia (CML), according to Monica Bocchia, MD, Department of Hematology, University of Siena, Italy. "Despite high rates of clinical and cytogenetic remission achieved by imatinib [Gleevec], most patients still have some degree of molecular residual disease," Dr. Bocchia said at the 47th Annual Meeting of the American College of Hematology (abstract 167). Furthermore, she noted that discontinuation of imatinib (Gleevec) usually results in recurrence of leukemia.

A vaccine specific for Bcr-Abl protein, such as CMLVAX100, might be an alternative way to specifically target CML cells, and could help toward controlling or even eradicating minimal residual disease, she said. A further rationale for CMLVAX100 is that it is potentially immunogenic and is a tumor-specific antigen.

Dr. Bocchia's phase II trial included 31 CML patients who had had a stable minor, major, or complete cytogenetic response to conventional treatment with either imatinib (n = 23) or interferon (n = 8). After GM-CSF (granulocyte macrophage-colony stimulating factor) support, they received vaccinations at six 2-week intervals, plus further boosts 4 to 6 months later in some cases. Before receiving the vaccine, none of the patients were positive for the DTH peptide-specific skin test or for in vitro CD4+ proliferation.

At ASH, Dr. Bocchia reported DTH and CD4 responses on 29 evaluable patients who had received all six vaccinations. For the 21 patients with prior imatinib treatment, 16 were DTH+ and 19 had a CD4+ response. For the 8 with prior interferon treatment, 5 were DTH+ and 5 had a CD4+ response.

Reporting further results only on the 21 imatinib-treated patients, Dr. Bocchia said that among 10 patients who had a major or minor cytogenetic response at enrollment, at 3 months after the six vaccinations, 6 improved to a complete cytogenetic response (with 4 PCR negative); 2 more were improved, and 2 others remained with stable disease.

Among 8 patients who had a complete cytogenetic response at enrollment, 5 had greater than 1 log improvements (with 2 PCR negative), and 3 remained with stable disease. There were no responses among patients who had 100% Philadelphia chromosome positivity at enrollment.

Eight of the 21 imatinib-treated patients went on to receive three additional CMLVAX100 boosts over a period of more than 18 months. Among 7 patients who had been in the group of 10 with major/minor cytogenetic responses at enrollment, all had a complete cytogenetic response with 2 remaining PCR negative. The other patient in this group that received the vaccine boosts had had a complete cytogenetic response at enrollment and improved to PCR negativity.

Dr. Bocchia concluded that the vaccine induced CML-specific immune responses mediated mainly by peptide-specific CD4+ T cells. Analysis showed evidence of reduced minimal residual disease in most patients, with some complete molecular responses. She commented further that the 6-month interval of the vaccine "boosts" may have been insufficient and that intervals at a maximum of 3 months seem necessary to maintain the response. Upcoming trials will further evaluate CMLVAX100 and other peptide vaccines.