The third day of the American Society of Clinical Oncology (ASCO) 2010 annual meeting in Chicago was tailor-made for morn­ing people interested in mul­ti­ple myeloma.  The key myeloma-related activity on Sunday, June 6 was a morn­ing abstract session start­ing at 9:30 a.m.  Nine abstracts were pre­sented and discussed over the course of three hours.

The first two pre­sen­ta­tions dealt with Velcade (bor­tez­o­mib)-related re­search.

Dr. Antonio Palumbo of the Uni­ver­sity of Turin pre­sented the re­­sults of the first study.  It com­pared two regi­mens for the treat­ment of newly diag­nosed elderly myeloma patients.  The first regi­men in­volved initial treat­ment with four drugs: Velcade, melphalan (Alkeran), prednisone, and thalidomide (Thalomid) (VMPT) followed by main­te­nance ther­apy with Velcade plus thalido­mide (VT).  The other regi­men consisted of initial treat­ment with Velcade plus mel­phalan and pred­ni­sone (VMP) without main­te­nance ther­apy.  The re­­sults favored the VMPT+VT regi­men, and Dr. Palumbo argued that this regi­men should be­come the new standard of care for newly diag­nosed elderly myeloma patients.

Dr. Palumbo also be­lieves the re­­sults of this trial in­di­cate that weekly admin­istra­tion of Velcade is superior to the drug's standard dosing schedule, because weekly dosing seems to reduce the in­ci­dence of periph­eral neu­rop­athy (pain and tingling in the extremities).  This state­ment did not go unchallenged, how­ever, in the dis­cus­sion of the study by Dr. Ruben Niesvizky of Cornell Uni­ver­sity.  He said that Velcade should be admin­istered weekly only in cer­tain spe­cif­ic situations.

The sec­ond pre­sen­ta­tion was by Dr. Philippe Moreau of the Uni­ver­sity Hospital in Nantes, France.  The study com­pared two Velcade-based regimens as initial ther­apy prior to stem cell trans­plant in newly-diagnosed mul­ti­ple myeloma patients.  One regi­men in­cluded low-dose Velcade, low-dose thalido­mide, and dexamethasone (Decadron) (vTD), and the other regi­men in­cluded standard-dose Velcade and dexa­meth­a­sone (VD).  Based on re­sponse rates both before and after stem cell trans­plant, vTD appears to be the superior regi­men.  Patients on the vTD regi­men also ex­peri­enced periph­eral neu­rop­athy less fre­quently than those on the VD regi­men.

The next two pre­sen­ta­tions shed light on a par­tic­u­larly in­ter­est­ing and controversial issue: the role of stem cell trans­plants when treating mul­ti­ple myeloma.

This issue is addressed head-on in the third pre­sen­ta­tion,  also given by Dr. Antonio Palumbo.  The pre­sen­ta­tion reviewed initial results from a clin­i­cal trial with 402 newly diag­nosed myeloma patients.  All of the  patients re­ceived an initial round of treat­ment with Revlimid and low-dose dexa­meth­a­sone.  About half of the patients re­ceived fur­ther treat­ment with Revlimid, mel­phalan, and pred­ni­sone (MPR), while the other half re­ceived high-dose mel­phalan (MEL200) chemo­ther­apy and an au­tol­o­gous stem cell trans­plant.  In the final phase of the trial, which is still on­go­ing, half of the patients will re­ceive main­te­nance with Revlimid and half will not.

After 12 months, over­all sur­vival in the MEL200 and MPR patient groups is high and basically equal (98% and 97%, re­spec­tively).  There is also no statistically sig­nif­i­cant dif­fer­ence in re­sponse rates. However, Dr. Palumbo said there is evi­dence that the MEL200 regi­men seems to be better for high-risk patients, but the MEL200 patients did have a noticeably higher rate of serious side effects.

The fourth pre­sen­ta­tion, by Dr. Paul Richardson of Harvard Uni­ver­sity, reviewed the re­­sults of a study of the Revlimid+Velcade+dexamethasone (RVD) combination ther­apy for newly diag­nosed myeloma patients.  All 66 patients in the trial received 24 weeks of the RVD regimen.  After the initial ther­apy, patients who responded to treat­ment could re­ceive an au­tol­o­gous stem cell trans­plant or main­te­nance ther­apy.

The over­all re­sponse rate to the initial 24 weeks of RVD ther­apy was 100 per­cent.  The 18-month esti­mated over­all sur­vival rate was 97 per­cent across all patients in the study.  Just as im­por­tantly, there does not appear to be any statistical dif­fer­ence in either over­all sur­vival or pro­gres­sion-free sur­vival be­tween patients who re­ceived a stem cell trans­plant and those who did not.

Thus, in these new stud­ies, the data do not in­di­cate whether stem cell ther­apy is superior to ther­apy with a novel myeloma agent such as Revlimid, thalido­mide, or Velcade.

The next two pre­sen­ta­tions,  how­ever, provided im­por­tant evidence that main­te­nance ther­apy with a novel agent im­proves out­comes for myeloma patients who have re­ceived a stem cell trans­plant.

Both of the pre­sen­ta­tions reviewed results from trials where Revlimid was the main­te­nance ther­apy tested.  The first pre­sen­ta­tion, by Dr. Philip L. McCarthy of Roswell Park Cancer In­sti­tute in Buffalo, looked at results from a United States trial with more than 400 patients.  All patients in the trial re­ceived a stem cell trans­plant.  Half then re­ceived Revlimid as main­te­nance ther­apy, while the other half re­ceived only a sugar pill (placebo) as their "maintenance ther­apy."

The patients who re­ceived Revlimid main­te­nance ex­peri­enced more side effects than the patients on placebo.  However, there was an esti­mated 58% lower chance of disease pro­gres­sion in the main­te­nance patients com­pared to the placebo patients.  The over­all sur­vival rate is also higher among the Revlimid patients, but the dif­fer­ence is not statistically sig­nif­i­cant.

One telling statistic: Results were so fa­vor­able in the Revlimid main­te­nance ther­apy arm of the trial that, when given a choice in 2009, a large majority of placebo arm patients chose to switch to Revlimid main­te­nance ther­apy.

The other pre­sen­ta­tion about Revlimid as main­te­nance ther­apy was by Dr. Michel Attal of the Uni­ver­sity Hospital in Toulouse, France.  The study he discussed in­volved over 600 myeloma patients, all of whom re­ceived au­tol­o­gous stem cell trans­plants followed by con­sol­i­da­tion ther­apy with Revlimid.  The design of the French study was roughly similar to the U.S. trial discussed by Dr. McCarthy.  The French study, how­ever, started before the U.S. study, so it has longer-term data.

As in the U.S. study, main­te­nance ther­apy with Revlimid noticeably reduced the rate of dis­ease pro­gres­sion.  Three-year sur­vival was 88 per­cent among the Revlimid main­te­nance patients and 80 per­cent in the placebo patients.  Once again, though, this sur­vival dif­fer­ence is not statistically sig­nif­i­cant.

After Drs. McCarthy and Attal gave their pre­sen­ta­tions, Dr. Sergio Giralt of the MD Anderson Cancer Center in Houston commented on the talks by sharing his thoughts on how to use main­te­nance ther­apy in day-to-day prac­tice.  His first recom­men­da­tion was to use Revlimid main­te­nance ther­apy for high-risk patients or those who do not respond well to their stem cell trans­plant.  As for patients who respond well (have a com­plete re­sponse) fol­low­ing their trans­plant, Dr. Giralt feels the de­ci­sion is more dif­fi­cult, because there is not firm evi­dence that Revlimid main­te­nance extends patients' lives.  He did say that Revlimid appears to work equally well for patients who have had either thalido­mide or Revlimid in their trans­plant induction ther­apy.  At the same time, in re­sponse to questions from meeting attendees, Dr. Giralt said he would not switch patients to Revlimid who are cur­rently on thalido­mide main­te­nance ther­apy and doing well.

The seventh pre­sen­ta­tion of the morn­ing was by Dr. Bart Barlogie of the University of Arkansas for Medical Sciences (UAMS).  During his talk, Dr. Barlogie described how he and his UAMS colleagues are using ge­netic testing -- spe­cif­i­cally "gene ex­pres­sion profiling" -- to better identify spe­cif­ic types of high-risk myeloma patients.  This is im­por­tant, he said, because the new myeloma ther­a­pies introduced in the last 5-10 years have primarily ben­e­fited low-risk myeloma patients.  By better classifying the dif­fer­en­t kinds of high-risk patients, the UAMS re­searchers hope to find better ways to treat those patients.

Dr. Barlogie's pre­sen­ta­tion was followed by a pre­sen­ta­tion by Dr. Sagar Lonial of Emory Uni­ver­sity.  Dr. Lonial discussed the results of a Phase 1/2 clin­i­cal trial investigating elotuzumab as a po­ten­tial myeloma ther­apy.  The trial in­volved 29 patients who had re­lapsed or re­frac­tory myeloma.  They re­ceived elotuzumab as well as Revlimid and dexa­meth­a­sone.  The over­all resopnse rate to the treat­ment was 82 per­cent in all patients, and 95 per­cent in patients who had never been treated with Revlimid.  Median time to pro­gres­sion has not yet been reached after 8 months.

The final pre­sen­ta­tion of the morn­ing com­pared the im­pact on myeloma patients of two different bis­phos­pho­nate drugs: Bonefos (clodronate) and Zometa (zoledronic acid).  Bisphosphonates are often prescribed to myeloma patients to help reduce the risk of bone fractures and bone decay asso­ci­ated with mul­ti­ple myeloma.

In his pre­sen­ta­tion, Dr. Gareth Morgan of the Royal Marsden Hospital in London (United Kingdom) reviewed the re­­sults of a study involving almost 2000 myeloma patients.  The patients were given either Bonefos or Zometa in addi­tion to their anti-myeloma ther­apy.  Zometa proved to be more ef­fec­tive than Bonefos in preventing fractures and other "skeletal-related events," and the patients taking Zometa also had longer over­all sur­vival than those who took Bonefos (50 months vs. 44.5 months).  The in­ci­dence of osteo­necrosis of the jaw (ONJ) was higher, how­ever, in patients who took Zometa than in patients taking Bonefos (3.5% vs. 0.3%).  (Bonefos is not approved for sale in the United States, but it is generally avail­able in Canada, Europe, and Australia.)

Looking ahead to Day Four of the ASCO meeting, there is an educational session devoted ex­clu­sively to com­pli­ca­tions asso­ci­ated with myeloma and myeloma ther­a­pies. There also will be a poster session focusing on on­go­ing mul­ti­ple myeloma re­lated clin­i­cal stud­ies.  Look for the Beacon's summary of the day's events in another ASCO up­date some­time tomorrow.