June 4, 2009 (Orlando, Florida) — It has been nearly 10 years in coming, but at last there is a positive result with a vaccine approach to follicular lymphoma. Two other phase 3 clinical trials have failed, but the one that succeeded was reported during a plenary session here at the American Society of Clinical Oncology (ASCO) 45th Annual Meeting.
The results come from a study funded by the National Cancer Institute that involved 177 patients with follicular lymphoma who had achieved and maintained a complete response for 6 months after induction chemotherapy. From this group, the patients who were randomized to receive the vaccine showed a significantly improved median disease-free survival, compared with those who received a control vaccine — the improvement was 47% from 30 months to 47 months (hazard ratio, 1.6; P = 045).
The vaccine, known as BiovaxID (under development by BioVest International), is personalized for each patient to include a tumor-derived idiotype protein. It has been granted fast-track status by the US Food and Drug Administration and orphan-drug status by the European regulatory authority.
"We now have a new therapeutic agent with clinical activity that may be applicable to our patients," said lead author Stephen Schuster, MD, director of the Lymphoma Program at the University of Pennsylvania School of Medicine in Philadelphia. The vaccine induces cellular immunity, and so has a different mechanism of action from existing immunotherapies. Logically, it could be added on to both chemotherapy and other immunotherapy, although to "ascertain clinical benefit would require another clinical trial," he told Medscape Oncology.
This question of where the new vaccine fits alongside existing therapy is the main issue with these new data, said Ron Levy, MD, chief of oncology at Stanford University in California, and a pioneer in the field of idiopathic vaccine development.
In a discussion of the paper also held during the plenary session, Dr. Levy concluded that the question of whether the vaccine was effective would get a "qualified yes," in that the data were "positive in those patients in whom it was tested." But the answer to whether there is a role for this vaccine in today's treatment of follicular lymphoma is more of a "maybe," he said, adding that "there may be a role for this vaccine, but further evidence will be needed."
Chemotherapy Used Is Now Out of Date
One of the issues with the trial was that the chemotherapy regimen used to induce remission in these patients, which was popular at the time the trial started 8 years ago, has now been superseded. The trialists used PACE (prednisone, doxorubicin, cyclophosphamide, and etoposide), which was standard in 1990s, Dr. Schuster noted.
However, in more recent years, immunotherapy with rituximab (Rituxan) has become the standard of care for use in induction schedules. It has had a huge impact on the treatment of follicular lymphoma, as previously reported by Medscape Oncology.
Dr. Schuster wondered how the vaccine will fit into therapy in the postrituximab era, and whether there will be a role for it. He said that another trial is now planned in patients who will be treated with rituximab and chemotherapy. He made the point that "the vaccine uniquely recruits the patient's immune system to seek and destroy only tumor B cells," and also noted that the vaccine was very well tolerated. In contrast, rituximab depletes the body of all B cells — healthy B cells in addition to the tumor B cells — which can result in toxicity.
Another issue with the trial was that of patient selection. Dr. Levy pointed out that 234 patients were originally enrolled, but the randomized trial was conducted in the 177 patients who responded to induction chemotherapy with a complete remission and who managed to sustain that complete remission for at least 6 months before receiving the vaccine (some maintained it for up to a year). So the patients who made it into the trial were "the best of the best," he said.
Dr. Levy pointed out that the positive result came from a modified intent-to-treat analysis of the 177 patients who received the vaccine, and not of the original 234 patients enrolled in the study. But he added that this "seems like a logical thing to do, to consider only the patients who received the treatment."
Despite the reservations, Dr. Levy highlighted the fact that this vaccine trial was positive, whereas 2 others in follicular lymphoma have both been negative.
Dr. Schuster speculated that the reason his group succeeded is that they used the vaccine in patients who were in complete remission and who remained in remission for at least 6 months. In these patients, it appears that the vaccine managed to hold the residual disease in check. In contrast, previous trials used vaccine in patients who had achieved partial or complete responses, but not necessarily remission.
The end of the beginning.
The positive results from this trial — and for another vaccine in melanoma patients — that were presented at this ASCO meeting spell "the end of the beginning" for cancer vaccine therapies, Dr. Schuster told Medscape Oncology. He predicted that vaccine approaches will now be tested with more enthusiasm, and that the newer techniques of immunomodulation now available will enhance the results that have been seen so far.
Dr. Schuster reported receiving research funding from BioVest International. Dr. Levy has disclosed no relevant financial relationships..
American Society of Clinical Oncology (ASCO) 45th Annual Meeting: Abstract 2. Presented May 31, 2009.
Medscape Medical News © 2009 Medscape, LLC
Send press releases and comments to firstname.lastname@example.org.
Cite this: ASCO 2009: Vaccine in Follicular Lymphoma Produces Significant Effect - Medscape - Jun 04, 2009.