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There were about 450-500 in attendance. In her welcome address, Susie Novis, President, noted this was one of the largest seminars to date. Dr. Brian Durie was introduced; he in turn introduced Dr. Robert Kyle, the first speaker.
Robert Kyle, M.D., The Mayo Clinic: Dr. Kyle gave a fine presentation on MM diagnosis and monitoring. (Most of which we on this list are familiar with). He reviewed MGUS, Smoldering MM, various indicators, and the spectrum of tests and scans to employ. He noted that he does not feel the need to repeat BMB's unless there are other changes in indicators. B.J. Proteins should be checked every 6-12 wks and may be stretched as time goes on. A audience. MRI's were touched upon; Kyle hinted that he felt they are cost prohibitive. Dr. Durie interjected that he feels they are good as a comparitive baseline as X-rays "vastly underestimate the potentials of the disease."
Brian Durie, M.D., Cedars-Sinai, Los Angeles, Ca: The most interesting information was Durie's insistance that there are a variety of viral and bacterial cofactors or antecedent infections in MM that are worth treating with antivirals and antibiotics. He presented some anectodal evidence that Biaxin at 500 mg twice a day (one week on, one week off) can drive spikes down. He's detected evidence of Helicobacteria in blood of MM patients (the bacteria that are implicated in peptic ulcer disease), and this prompted him to try Biaxin. (Some folks on the MM list are already doing this). He also suggested that it might be worth trying the antivirals that are used against the herpesvirus family (like gancyclovir) in smoldering MM and possibly in MGUS
Other interesting new approaches mentioned by Dr. Durie: MMPI (metalloprotease inhibitors not the Minnesota Multiphasic Personality Inventory) to reduce or prevent destruction of bone matrix (In trial in France). (Blood Vol 90, No 4, Aug 15, 97 PP 1649- 1655)
MMP - Metalloproteinases - enzymes which destroy bone. There are new drugs to possibly block MMP, e.g. Batimastat which maybe can be combined with Aredia.
Idarubicin instead of vincristine (given by mouth instead of by infusion), and given with dex.
Etopiside instead of vincristine.
Vitamin D3 inhibitor (EB1089) (in
trials in Europe) in combination with dex. Blood Vol 88 No 12 (December 15),
1996: Pp 4659-4666
Development of monoclonal antibodies to MM cells for vaccine trials.
PSC833 for multidrug resistant MM (new drug from Sandoz/Novartis).
Other RNA inhibitors worth looking at: tamoxifen and trans-retinoic acid. Donor lymphcyte infusions to get a limited graft vs myeloma effect.
There are currently 48 drugs being developed for use in breast cancer. Multiple Myeloma? five drugs.
Everyone should drink a lot of water! Flush those kidneys! MM patients who drink a lot of water live longer (Dr. Bergsagle). People with lots of infections should consider some gamma globulin shots.
Greg Mundy, M.D., University of Texas Health Science Center, San Antonio: Dr. Mundy spoke on Bone Disease. With his accent (Australian ?) and skeletal slides, it was an interesting talk. " If we can manage the bone-disease aspect, we can make Myeloma a much more benign disease." MM cells activate osteoclasts which resorb bone -- so on and so forth... He did note he feels the best treatment aim is to cytotoxically kill the myeloma cells. But in the face of our current limitations (most notably we can't kill them all) the drugs which inhibit the resorbtion process are the best second line therapy. He recognized but added that it's not proven whether bisphosphonates limit MM growth. He pointed out some new, more powerful bisph's on the horizon: Risedronate and Ibandronate still a few years away. He gave a history of the biphosphonates...and he said we don't have definitive answers on how much, how long, or which ones - though he favors pamidronate. Drugs beyond bisphosphonates? Yes. Better drugs to inhibit osteoclasts are probably (unfortunately) about a clear decade away. Lastly, AVOID FRACTURES. He made a plug for the RDA of Calcium and Vit D. We should expect more trials on the newer bisphos's. (Dr. Durie suggested that good old Fosamax might be worth a try for those not ready for Aredia). Above all, try and stay active.
Mohammad Hussein, M.D., The Cleveland Clinic:
Dr. Hussein talked on standard therapy since Ken Anderson. M.D. (Dana Farber) was unable to attend. Much of Hussein's presentation focused on modifying standard approaches; he indicated that the Cleveland Clinic was now concentrating on extending the plateau phase as opposed to working on a cure. They are doing considerable concentration on the (somewhat controversal) stimulation of plasma cells with IL-6 and subsequent timing of chemo for maximum MM cell kill-off. He also noted that attention is being given to IL-2 as a role in maintenance. "80% of patients with high serum levels of IL-2 are alive and well by 5 years from diagnosis and only 13% with low levels." In the questions segment, there was a question on alternative therapy. All the Dr.s agreed that alternate therapy should not replace medical treatment, rather should compliment it. And check with your MD. Dr. Durie stated that he felt alternative measures were indeed an important personal choice of the patient. Kyle made mention that patients should strive to enter prospective & randomized studies and trials of MM treatment for the benefit of increased knowledge and treatment progress. He stated Dex was 80% of the effect from VAD; and that Dex alone is good for those with low WBC's and Platelets.
Joseph Michaeli, M.D., Sloan-Kettering, NYC:
Dr. Michaeli spoke on High dose therapy with transplant or stem cell rescue as he more accurately likes to put it. Combo chemos show no survival benefits over basic MP. High dose, in his opinion, is best used refractory, relapsed, and salvage therapies. The French study indicates superior 5 yr survival of HDT and rescue over "conventional chemo." Best thing would be to determine which sub-groups would be most lkely to benefit from rescue/transplant. Favorable factors include: <1yr dx'd, remission, single type prior chemo, 6 or less cycles of prior chemo.
BM purging and purification is still controversal.The value of TBI is uncertain...there is no evidence that it adds benefit. Dr. Durie noted an Italian study that indicates those with high B2m and labeling index may have been helped more by BMT over those with low B2m and labeling index who may not have received a similar return on investment. Both doctors seemed to agree that one might want to hold off on the double transplant and save the second one for a "rainy day."</P.The question of transplant or not to transplant is still open: good prognosis patients are just coming to the end of their expected survivial times, and we'll have to wait to see if transplanted good patients do as well as nontransplanted good patients. Harvest those stem cells when in remission and hold on to them for a rainy day. This is especially important in newly diagnosed patients with advanced symptomatic disease. The stem cells are good for years. On a transplant question, Kyle also noted that the French study released this year showed no difference was found between early transplants and those patients who delayed until relapse occured.
Finally, pick a transplant center with great care. Ask questions. How many have they done? What are the outcomes? What will be the flexibility on protocol? And of course location is a consideration one must be comfortable with. It helps greatly if you know if you are heading down the BMT road someday as treatment selections today will depend on your plans.
William Freidenberg, M.D.,
Dr. Freidenberg spoke on Multi Drug Resistance. Much of the discussion centered around a substance called P-glycoprotein or P-GP 170 which acts like a pump to pump chemo out of the myeloma cell thereby preventing cell death. Almost all VAD patients develop a resistance to chemo. Drugs used to inhibit this pump, known as MDR modulators include Verapamil, Cyclosporin A, and most recently PSC-833. At effective levels, Verapamil is too toxic. Cyclosporin A in the same regard can cause severe kidney damage, and has a high risk of infection as it is a powerful immunosuppressant. Thus PSC-833. Still in study phases. Phase II now in progress but closed. New study by SWOG to begin Sept 15. Phase III studies are imminent. One effect of PSC-833 is its cerebrum dysfunctions - that is, the possible loss of balance. There are protocols for multidrug resistant MM going on - look on the web.
Next, recipients of the 1996 Brian D Novis Research Grant & Chiron Therapeutics Research Grant reported, Doctors Rena Feinman & P. Lief Bergsagle respectively. Leif Bergsagel was articulate in his discussion of the transformation of cells from normal to malignant MM cells. "technical content of research omitted." Bergsagel reiterated the importance of drinking 3 liters of fluid a day!
A new event this year was a Patient Panel with Dr. Durie as the moderator. Four patients sat in the front and described their MM histories and took questions. The panel included Pat Lehmeier dx'd 1988 with a 15,000 Igg level. MP and Interferon. Don Springer, who also organizes a Spring golf tournament to raise funds for the IMF- (contact the IMF for info) - dx'd '91, 3 rounds of MP, interferon, and extensive doctor-controlled vitamin/nutrient treatment. Bill Solomon dx'd '86, and I believe only 1 round of MP back in '89-'90. And Rudy Martina dx'd '93, M2 protocol, relapse in '95, 2 rounds of VAD, PBSCT. It was an interesting feature of the seminar.
Congratulations to Jan Jukes, IMF special events coordinator and Myeloma Today editor. All volunteer. Jan is the recipient of the Francesca Thompson Outstanding Service Award in recognition of her efforts, the award presented by Mike Katz.
The "Break-out Sessions" were held in smaller rooms; each had a different doctor and topic; you could roam from one to another at will. Each room hosted a topic which had been discussed earlier, but now there was a chance to review, learn more, or ask additional and/or personalized questions.
Break-Out Session - Headed by Dr. Joseph Michaeli, Sloan-Kettering: The impression was that he has been treating MM patients for some time. He made the provocative statement that some patients are truly cured of myeloma. He was questioned as to why he felt this way & he said that he has seen enough cases where this seems to have been the case. He further stated that many of these cases seem to be with patients who were treated with Gallium Nitratein a trial they did some years ago. 17% of the patients who received this treatment 9 years ago are "cured". At the same time, he cautioned not to make to much of this; they are looking into doing some further studies. What I find interesting is that this was originally given to increase bone density. Is the the reason Gallium Nitrate may be effective similar to the reason bisphosphanates may be effective?
He also said that patients shouldn't have TBI. It does more harm than good. "ed. note: when I saw Dr. M in early 1994, they were still using TBI". With allogenic transplants milder chemo is more effetive since it is safer & you still get the graft vs myeloma effect. Instead of VAD they are testing EAD where E is Etopside. After 3 rounds of EAD, patients get high doses of cytoxin & their stem cells are harvested & stored. Some patients are to have additional treatment with melphalan & another harvest made. After high dose melphalan their immune system will be restored with the cells harvested after the earlier melphalan treatment, but if that didn't work they would use the cells from the first harvest. This study is intended to see if treating a patient with melphalan before harvest leads to better results. Dr. Michaeli said they should have the answer in about 8 years.
Opinions/comments from those attending: Durie's implied treatment goal is to contain disease, not look for a definitive cure. He wants to turn MM into something chronic and manageable, and is willing to be creative in approaching this goal, especially if the patient is also willing to try stuff and understands the underlying logic.
Other docs have more radical and/or more rigid approaches to the disease, or are likely to stick to the tried and true. Other types of patients might be very uncomfortable with therapeutic approaches which seem improvisatory and/or untested, or want to go-for-broke up front.
Vicvfl@aol.com (Mike V.),
ZMontana@aol.com (Chuck Newman)
Edited and recompiled by: Cathy L. firstname.lastname@example.org
More IMF Seminar Notes: http://www2.gasou.edu/facstaff/jariail/myeloma