Yesterday -- Saturday, June 5 -- was the sec­ond day of the American Society of Clinical Oncology (ASCO) 2010 annual meeting in Chicago.  It was a busy day in terms of re­search posters and pre­sen­ta­tions re­lated to mul­ti­ple myeloma.  As a re­­sult, there is a lot of ground to cover in this up­date.

Almost 40 myeloma-related posters were up for meeting attendees to view during the daytime poster session on "lymphoma and plasma cell disorders."  Among those 40-or-so posters, six con­cerned re­search done by the myeloma team at the Uni­ver­sity of Arkansas for Medical Sciences (UAMS), and two of those six stood out in par­tic­u­lar.  Both of those stud­ies con­cern the Total Therapy pro­gram that is being continually up­dated and in­ves­ti­gated at UAMS.

In the first ^[1] of the two UAMS posters, researchers followed 231 patients who had undergone tandem stem cell trans­plants. The key re­­sult: 45 patients are still alive after 17 years. Those re­­sults sig­nif­i­cantly exceed cur­rent national averages in the 10 per­cent range for 10-year sur­vival.

The sec­ond key UAMS poster ^[2] examined the sec­ond and third iterations of the Total Therapy regi­men (TT2 and TT3), comparing those who con­tinued on the rec­om­mended post-transplant main­te­nance protocol of Velcade ^[3] (bor­tez­o­mib), thalidomide ^[4] (Thalomid), and dexamethasone ^[5] (Decadron) to those who ended maintenance ther­apy early. The study re­­sults in­di­cate that patients who dropped ther­apy earlier had a shorter time to their next re­quired treat­ment.  Or, to put it another way, patients who stayed on main­te­nance ther­apy longer delayed the return of their myeloma.

Among the rest of the posters at the session, one ^[6] from the Euro­pean Cancer Network deserves mention.  The study analyzed results from six pre­vi­ously con­ducted clin­i­cal trials.  It confirmed that adding thalido­mide to melphalan ^[7] (Alkeran) and prednisone ^[8] for previously untreated elderly myeloma patients sig­nif­i­cantly im­proves time to pro­gres­sion and over­all sur­vival.

The Mayo Clinic also had an in­ter­est­ing poster ^[9].  It com­pared three drug regi­mens for newly diag­nosed mul­ti­ple myeloma patients: Revlimid ^[10] (lena­lido­mide)+dexamethasone (RD); cyclophosphamide ^[11] (Cytoxan)+Revlimid+dexamethasone (CRD); and cyclo­phos­pha­mide+Velcade ^[3] (bor­tez­o­mib)+dexamethasone (CyBorD).  The re­­sults rather clearly in­di­cate that the CRD com­bi­na­tion is inferior to the other two regi­mens.  As to which of the other two regi­mens looks best, the authors come down in favor of CyBorD.  Yet the data the authors present in their poster seem a bit less clear on this point: median pro­gres­sion free sur­vival, for example, was longer for the RD patients than for CyBorD patients (3.2 years vs. 2.6 years).

In addi­tion to the poster session, there also was an im­por­tant evening symposium whose theme was "Novel Therapies for Myeloma." During the symposium, the re­­sults of four recent clin­i­cal stud­ies were pre­sented and then discussed.

The first study ^[12] pre­sented was the Phase 2 carfilzomib ^[13] single agent study in re­lapsed/refractory patients. Carfilzomib is a pro­te­a­some in­hib­i­tor like Velcade, but stud­ies thus far have in­di­cated that it may have fewer side effects than Velcade.  There is there­fore a lot of interest and "buzz" about car­filz­o­mib at this year's meeting.

Response to car­filz­o­mib in the Phase 2 study was much higher in Velcade-naïve patients (45-55 per­cent versus 21 per­cent), which is per­haps not surprising given the similar way that car­filz­o­mib and Velcade work. Duration of re­sponse was sig­nif­i­cant even in patients achieving only minimal re­sponse. Side effects were described as clin­i­cally man­ageable. Due to a lack of sig­nif­i­cant adverse events, Dr. Ravi Vij of Washington Uni­ver­sity (St. Louis) said that the re­­sults sug­gest car­filz­o­mib is fa­vor­able for use in com­bi­na­tion with other treat­ments. Addi­tionally, due to the lack of side effects, there is interest in studying car­filz­o­mib at much higher doses.

The sec­ond study ^[14] pre­sented was a Phase 1b study of panobinostat ^[15] in com­bi­na­tion with Velcade and dexa­meth­a­sone in re­lapsed/refractory patients. The over­all re­sponse rate was 70 per­cent over­all, and 60 per­cent in patients who have failed treat­ment with Velcade. The re­searchers have only collected about three months of data, so no time to pro­gres­sion data have been gathered yet. A sig­nif­i­cant per­cent of patients ex­peri­enced low blood cell counts, but Dr. Kenneth Anderson of Harvard Uni­ver­sity said these side effect cases were man­ageable. Dr. Anderson also said that this is the most re­spon­sive com­bi­na­tion yet observed among patients who have failed Velcade treat­ment.  A Phase 3 trial of panobinostat and Velcade vs. Velcade alone is on­go­ing.

The third study ^[16] pre­sented was a Phase 2 study of pomalidomide ^[17] in com­bi­na­tion with dexa­meth­a­sone in heavily pre-treated myeloma patients. Poma­lido­mide is a drug that is chemically re­lated to both thalido­mide and Revlimid. The pre­sen­ta­tion was made by Dr. Martha Lacy of the Mayo Clinic. The over­all re­sponse rate to poma­lido­mide was 26 per­cent, and 54 per­cent achieved at least a minimal re­sponse. Time to re­sponse was only 1 month, which is con­sidered very rapid. Dr. Bart Barlogie of the Uni­ver­sity of Arkansas sug­gested that poma­lido­mide plus dexa­meth­a­sone might be used as front-line ther­apy for myeloma since the re­sponse is so rapid. Over­all sur­vival was 86 per­cent at 6 months. Re­sponses were similar in low and high risk patients, which is atypical.

Dr. Sagar Lonial of Emory Uni­ver­sity commented favorably on the poma­lido­mide re­­sults, saying "These patients were some of the most pre­vi­ously and heavily medicated of any patients ever in­cluded in such a study." He con­tinued: "These are truly impressive re­­sults."  Future poma­lido­mide stud­ies are likely to examine the safety and ef­fi­cacy of a higher dose of the drug.

The fourth study ^[18] pre­sented was a Phase 1 trial of elotuzomab ^[19] plus Velcade in re­lapsed/refractory patients. The overall re­sponse rate was 48 per­cent, and 64 per­cent achieved at least a minimal re­sponse. Time to pro­gres­sion was 9.5 months over­all and also in Velcade-refractory patients. The most common side effects were fatigue, anemia, and diarrhea. The most common serious side effect was lymphopenia (lymphocytopenia, or low levels of lym­pho­cyte white blood cells). The elotuzumab plus Velcade com­bi­na­tion appeared to be well tol­er­ated with no dose limiting toxicities. The re­searchers be­lieve that elotuzumab and Velcade may have a syn­­er­gis­tic effect.

Overall, there was a lot of ex­cite­ment about the re­­sults pre­sented at the evening symposium.  Many of the symposium attendees came away with a sense that it may not be very long until there are sev­er­al new treat­ment op­tions for multiple myeloma patients.