This year 5,453 abstracts were submitted to the American Society of Hematology (ASH), of which over 200 dealt exclusively with myeloma plus more including myeloma as part of a larger study. In addition, there was a "Myeloma: Corporate Super Friday" event on Friday, December 7th, as well as a Physician Education Session for myeloma on Saturday, December 8th (full text accessible on IMF website at www.myeloma.org).
The presented abstracts specifically on myeloma included 1 plenary session oral presentation (the "top" submitted abstract as judged by the program committee), 49 oral presentations, as well as 152 poster presentations distributed December 8th -10th. Detailed commentary on the sessions is available via a special ASH edition of the Myeloma Minute on the IMF website. The following is an overview of highlights from the various sessions.
Plenary Oral Presentation
"Combining an Allogeneic Graft-vs-Myeloma Effect with High-Dose Autologous Stem Cell Rescue in the Treatment of Multiple Myeloma" (Abstract #1822) was presented by David G. Maloney, Firoozeh Sahebi, Keith E. Stockerl-Goldstein, et al. This study involved 32 previously treated patients who had relapsed. The "mini-allo" or non-myeloablative allogenic transplant protocol consisted of first a typical auto stem cell transplant using high dose melphalan (200mg/m2) followed by total body irradiation and immunsuppressive therapy, along with the non-myeloablative graft of immune cells from an HLA identical sibling. The excitement is that the added graft-vs-myeloma effect resulted in 53% complete remissions plus 31% partial remissions, giving an 84% overall response rate. The caution is that 6/32 (19%) of patients have died with follow-up of about 1 year, although not all from direct transplant complications. This is less than the 30% or greater mortality possible with a full allogeneic transplant, but still substantial and very high compared to the typical very low risk (1% to 5%) of mortality from standard autotransplant. Nonetheless, this is an important step forward in trying to develop a safer technique to achieve the clearly important graft-vs-myeloma benefit. Further refinements and studies will be required.
Oral Sessions Highlights
The oral sessions on Monday covered numerous "pre-clinical" or laboratory based projects. Time will tell if useful therapies can emerge. A whole session dealt with genetic profiling via gene array technology and/or standard genetics or FISH. Besides chromosome 13, chromosomes 22 and 1 emerged as being prognostically important. It will take some time to assess if the molecular profiles will help in treatment decisions and/or patient outcomes. Expression patterns of genes were correlated with good and poor prognosis. The critical question is if new useful treatment targets can be identified and used to patient advantage.
The greatest excitement concerned the trials with proteasome inhibitor PS-341 (Millennium) and the new thalidomide analog, Revimid® (Celgene). Results from the first 54 patients entered into the phase II PS-341 study for relapsing/refractory myeloma were presented. Half of the patients responded by SWOG criteria with an additional 35% of patients showing evidence of benefit in this multi-institutional study. Patient examples from St. VincentÕs Cancer Center in New York (Dr. Sundar Jagannath, Principal Investigator) were presented to illustrate dramatic benefit in patients who had received multiple prior therapies. One patient responded after 14 prior treatments. Some worsening of pre-existing neuropathy was a toxicity concern. Since the full 200 patients are still under review and follow-up is short, additional details of efficacy and toxicity will be forthcoming in 2002. The correlation between molecular profiles and response will be awaited with particular interest, as will details of remission duration.
The Revimid® (a.k.a., IMid) results were presented from both Dana-Farber and Little Rock. The numbers of patients in these Phase I evaluations were rather small (Boston, 26 patients; Little Rock 15 patients). Although responses occurred in a majority of patients, the impact of therapy was hard to assess from the data presented. Importantly, there was no neuropathy, but unfortunately there was unexpected toxicity most notably neutropenia, which appeared to be cumulative at the 25mg and especially the 50mg/day doses. Further studies are required and planned. The full potential for Revimid® was less clear than for the PS-341. Obviously this was the Phase I stage for Revimid® versus Phase II for PS-341. The availability of an oral agent, such as Revimid®, with the efficacy of thalidomide, but lacking the neurotoxicity is widely anticipated. Details about availability of PS-341 and Revimid® will be posted on the IMF website's Myeloma Minute and the new clinical trials matrix. Currently several corporate and investigator initiated protocols are planned. For 2002, both agents will only be available through Phase II/III clinical trials. As of now, the Revimid® will only be available as part of randomized clinical trials (i.e., less accessible to patients who may specifically need Revimid®). Hopefully, additional studies, for example evaluating the best dose of Revimid®, will make the drug more available for patients.
Besides the very large number of abstracts on molecular and genetic topics, one of the most popular topics was thalidomide. Twelve posters (#681-692) dealt with thalidomide. The Little Rock Group (#681) again emphasized the caution of potential deep vein thrombosis (thrombophlebitis) in patients receiving the combination of thalidomide plus adriamycin. This type of blood clotting was not life threatening and proved treatable and potentially preventable with anticoagulant therapy. The majority of abstracts dealt with issues related to the dose and scheduling in both monotherapy and combination approaches. The consensus from several posters was that a median effective dose in monotherapy was 200 mg/day. Some patients (~30%) require less (e.g., 50mg/day: #688) and most patients cannot tolerate and do not need more (#684). In combination with pulsed dexamethasone, thalidomide is very effective both as frontline therapy and at relapse. Again, 200mg/day or less is the most frequent dosing discussed or presented.
Predictors Related To Transplant
As the role of high dose therapy with stem cell transplant is evaluated in detail, there is increasing interest about prognostic factors in this setting. Abstracts #698 and #700 dealt with outcome and predictors in patients treated with high dose therapy and transplant. Age less than 55 and good pretreatment performance status (#698) predicted good outcome. When outcome was assessed by adding up the total periods of remission achieved by a patient (#700, a new term called period of "discontinuous remission") the best predictors were serum b2 micro globulin level and serum albumin as per a recent SWOG analysis of overall outcome. ASH 2001 was a very productive and informative meeting for those interested in myeloma. 2002 promises to be a banner year for new understanding and therapeutic advances.
Twenty-four participants from around the world attended the IMF Scientific Advisory Board meeting held at ASH 2001.
ASH 2001 IMF Reception & Dinner
The IMF wishes to thank its Directors and Scientific Advisors for their invaluable participation at the ASH 2001 IMF events and their hard work and dedication on behalf of the foundation and the myeloma community year round.
Dr. Raymond Alexanian
Dr. Kenneth Anderson
Dr. Bart Barlogie
Dr. Regis Bataille
Dr. James Berenson
Dr. Daniel Bergsagel
Dr. Willian Bensinger
Dr. Joan Blade
Dr. J.A. Child
Dr. Meletios Dimopoulos
Dr. Brian G.M. Durie
Dr. Vania Hungria
Dr. Robert Kyle
Dr. Jayesh Mehta
Dr. Gareth Morgan
Dr. Angelina Rodriguez-Morales
Dr. Amara Nouel
Dr. Martin Oken
Dr. David Roodman
Dr. Jesus San Miguel
Dr. Seema Singhal
Dr. Brian Van Ness