Beta-alethine: TNF alpha, Antitumor Effects and Delayed Type Hypersensitivy in Follicular B-Cell Lymphoma.
W. H. Miller, Jr.1, S. Caplan1, C., Shustik2, A. McQuillan1*, F. Sicilia1*, S. Mayerson3* and F. Taub4*.1 Jewish General Hospital, McGill University; 2Royal Victoria Hospital, McGill University; 3Dovetail Technologies, Inc., 4LifeTime Pharmaceuticals, Inc.
Objectives: Beta-alethine (BT, Betathine™, or Beta LT™) increased delayed type hypersensitivity (DTH), vaccine response, and survival, or reduced tumors in murine models. A Phase I/II trial was initiated in patients (pts) in order to assess safety and to obtain preliminary evidence supportive of an immune mechanism of action and antitumor activity.
Design & Methods: Pts with histologically confirmed, measurable, low grade B cell lymphoma after maximal response to previous treatment (6 pts) or with indolent disease not yet requiring therapy (2 pts) were treated with 2ug/pt every 14 days for 6 doses (85 days unless extended).
Safety Results: To date 8 lymphoma pts and, in a sister protocol, 6 myeloma pts (5 post stem cell transplant) have received BT for periods up to one year. No pt has BT attributable side effects.
Immune Results: Previously BT has been reported to increase tumor necrosis factor alpha (TNFa) expression on human T cells and monocytes in culture. Compared to pre-study, the majority of pts on BT show increased TNF expression on the surface of lymphocytes. Half were <4% (mean=17%) on day 1 and all were >25% at end of study (mean=44%); paired t-test p=0.026.
Tumor results: Eight pts were evaluated. Maximal response in total bi-dimensional tumor measurements include one pt with 53% decrease, 1 with 25-50% decrease, 1 with 0-25% decrease and 5 with increasing disease (7-156%). Data to date show an association between pre-study DTH and subsequent tumor reduction. Three of 4 DTH+ pts had >10% decreases in tumor while 3 of 4 DTH- pts had >10% increases in disease (Fisher’s Exact test at D85 p=0.05, one-tailed). (One pt in each group was stable [+ 10%]).
Conclusion: Data to date indicate BT at this dose is non-toxic, increases surface TNF, and can have anti-lymphoma effects.
Oral presentation at the ISH 2000 (28th International Congress)
Toronto, Ontario, August 2000