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Biotech / Medical : CLTR COULTER PHARMACEUTICAL -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (431)	12/5/1999 12:32:00 PM
From: Biomaven	Read Replies (2) \| Respond to of 666

Rick, This Rituxan ASH abstract may shed a little light on the issue of ongoing response: [390] RESPONDERS TO RITUXIMAB SHOW CONTINUED TUMOR REGRESSION OVER TIME AND A PROGRESSION-FREE SURVIVAL THAT CORRELATES WITH RESPONSE CLASSIFICATION. A. J. Grillo-Lopez, P. McLaughlin, M. Czuczman, D. Maloney, S. Liu, B. Alkuzweny, C. White. IDEC Pharmaceuticals Corp., San Diego, CA; MD Anderson Cancer Center, Houston, TX; Roswell Park Cancer Center, Buffalo, NY; Fred Hutchinson Cancer Center, Seattle, WA. Rituximab has mechanisms of anti-lymphoma action that differ significantly from those of chemotherapeutic agents: direct - induction of apoptosis and chemosensitization, and indirect - CDC and ADCC. Some of these result in an immediate effect on the lymphoma cells as evidenced by the profound and selective B-cell depletion occurring immediately after the first infusion and tumor regression seen within the first 7 days of treatment. Others may result in a more prolonged and sustained effect depending at least partially on the quality and availability of effector cells (and complement) and the levels of circulating antibody achieved and sustained over time (reflecting saturation of antigenic sites). Pharmacokinetic studies in Rituximab monotherapy trials have revealed the presence of circulating antibody as far out as 6 mos. from first infusion. Correspondingly, peripheral blood B-cell depletion lasts up to 6 mo. with recovery between 9 and 12 mos. Pts with relapsed or refractory, low grade or follicular NHL received Rituximab at 375 mg/m2 by IV infusion q wk for 4 doses. There were 76 responses in 150 evaluable pts and PFS was 13.2 mos. (median). Responders showed a rapid decline in the mean of the sum of the products of the perpendicular diameters of all measurable lesions (SPD) with a slower decline continuing for 10 or more mos. Kaplan Meier PFS curves for CR vs PR pts show a significant difference favoring CR. Similarly, in a trial of Rituxan combined with CHOP with 38 responses in 38 evaluable pts and median PFS not reached after 41.1+ mo., responders showed a rapid decline in the mean SPD with a slower decline continuing for 10 or more mos. Additionally, Kaplan-Meier PFS curves for CR vs PR pts show a significant difference favoring CR. The tumor regression seen with Rituximab appears to continue for months after completion of therapy. Although the median time to response is 50 days, some pts with stable disease will later achieve a PR. Also, some pts initially with a PR will later achieve a CR. Thus, pts with stable disease should be observed with no further therapy if they are showing continued regression as they may become responders. Poster Session: Indolent Lymphoid Malignancies and Additional Therapeutic Approaches (9:45 AM-7:30 PM) Presentation Date: Saturday, December 4, 1999, Time: 9:45AM, Room: Hall B, Poster Board Number: 390 It's after presentation date, so I guess it's OK to post ASH abstracts in full now. Peter

To: scaram(o)uche who wrote (431)	12/6/1999 6:26:00 PM
From: Gordon James	Read Replies (1) \| Respond to of 666

Rick, I'm adding to the chorus of "thank yous"... The thank-yous are going to turn into hisses soon if I don't sit down and get more of my observations posted! Unfortunately haven't had time yet, got back home yesterday evening and now leaving for a 3-day business trip this afternoon. But I'm going to try and dribble out some more over the next few days, and I'm looking forward to getting feedback from yourself and the other knowledgeable folks here to help sort out some of these observations. Especially on what you tipped me off to, right now I'm blown away with it so far, and trying to finish getting up to speed so I don't sound stupid talking about what I heard... why were 24 patients non-evaluable? Good question. Here's perhaps part of the answer for that - from my printed copy of the poster, the last sentence reads: All patients treated and evaluated exhibited a response during the study. Additional patients have been treated in the study and will be assessed. It will certainly be important to see the results from the other 24 patients. Hopefully there aren't a lot of them that were treated during the same time frame as the 14 treated above, but not evaluable due to dropping out, death on study, etc. Ideally the other 24 were treated too recently to have completed assessment and reporting, and are all among the "additional patients who have been treated and will be assessed", but hard to say for sure from the info at hand. Another question I wish I'd asked! But I did pose my question at the CLTR booth about whether PCR was done to detect molecular remissions (as requested by V1), and they are supposed to be having someone get back to me, hopefully Dr. Leonard. I'll ask a little more about this at that point, or perhaps just try and email him directly. Cheers, Gordon