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ASCO 2011 Multiple Myeloma Update – Day Four

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Published: Jun 8, 2011 6:13 pm

Monday was the fourth day of the American Society of Clinical Oncology (ASCO 2011) annual meeting in Chicago.  Although the meeting concluded yes­ter­day, Monday was the last day of the meeting that con­tained any myeloma-relevant ma­teri­al.

The morn­ing started with a session recapping highlights of the meeting from Sunday.  Dr. Ivan Borello from the Johns Hopkins Uni­ver­sity School of Medicine was invited to give a 15-minute pre­sen­ta­tion recapping the myeloma highlights (see Part 1 and Part 2 of The Beacon’s Day Three up­date for more in­­for­ma­tion).

The rest of the myeloma-related in­­for­ma­tion was pre­sented during poster sessions in the morn­ing and afternoon.  The highlights in­cluded re­­sults from a num­ber of clin­i­cal trials studying po­ten­tial new drugs for the treat­ment of myeloma, in­­for­ma­tion about a couple of clin­i­cal trials that are still recruiting par­tic­i­pants, and an analysis of sec­ond­ary cancers in patients treated with Revlimid (lena­lido­mide).

One of the posters was on pomalidomide (CC-4047), a drug chemically re­lated to Revlimid and thalidomide (Thalomid) that is being devel­oped by Celgene for the treat­ment of mul­ti­ple myeloma and re­lated blood disorders.  Poma­lido­mide and car­filz­o­mib are the two new myeloma drugs that are furthest along in clin­i­cal trials and most likely to be approved for use in the United States soon.  Preliminary re­­sults from the Phase 2 study pre­sented during the poster session showed that poma­lido­mide plus dexamethasone (Decadron) is ef­fec­tive in re­lapsed myeloma patients, in­clud­ing those pre­vi­ously treated with Revlimid (abstract). Among the 61 par­tic­i­pants, 35 per­cent responded, most within the first or sec­ond cycle of ther­apy. After about four months, almost all par­tic­i­pants (97 per­cent) were still alive and two-thirds had not yet progressed.  Side effects mainly in­cluded low blood cell counts and a few cases of fatigue, blood clots, high blood sugar levels, and pneu­monia.

There were also two posters on elotuzumab, a new drug that is being devel­oped by Bristol-Myers Squibb for the treat­ment of mul­ti­ple myeloma.  One of the posters in­cluded re­­sults from a Phase 1 study of elotuzumab, Revlimid, and low-dose dexa­meth­a­sone in 29 re­lapsed / re­frac­tory myeloma patients (abstract). Three doses of elotuzumab were tested. The over­all re­sponse rate was 82 per­cent for all patients and 95 per­cent for Revlimid-naïve patients. At the highest dose tested, most patients had still not progressed after 16 months of follow-up. The com­bi­na­tion was generally well tol­er­ated with serious side effects mainly lim­ited to low blood cell counts due to Revlimid and in­fusion site reac­tions during the first cycle due to elotuzumab. Other common side effects in­cluded fatigue, diarrhea, nausea, and con­sti­pa­tion. The middle dose of elotuzumab appeared to have a slightly better re­sponse rate than the highest dose, so a Phase 2 study that was pre­sented yes­ter­day during the oral session is cur­rently fur­ther eval­u­ating the middle and highest doses.

Another study pre­sented during the session helped provide a better under­stand­ing of how elotuzumab works (abstract).  Elotuzumab recog­nizes cer­tain pro­teins called CS1 that are on the surface of myeloma cells, but not on nor­mal cells. Scientists be­lieve this recognition then triggers im­mune cells known as natural killer cells to kill the myeloma cells.  The study sug­gests that elotuzumab also directly activates natural killer cells by recognizing the same CS1 pro­teins on the surface of the natural killer cells.  Once elotuzumab activates these natural killer cells, they then appear to kill the myeloma cells.

There were also two posters on panobinostat (Farydak), an oral drug being devel­oped by Novartis for the treat­ment of a num­ber of solid tumors and blood cancers, in­clud­ing mul­ti­ple myeloma.  One of the posters in­cluded re­­sults from a Phase 1b study of panobinostat plus Velcade (bor­tez­o­mib), and in some cases dexa­meth­a­sone, in 62 re­lapsed / re­frac­tory myeloma patients (abstract). The optimal dosing de­ter­mined during this trial was 20 mg panobinostat three times a week for two weeks followed by a week off. The over­all re­sponse rate was 55 per­cent, and 40 per­cent of Velcade-refractory patients achieved a partial re­sponse. Serious side effects were mostly low blood cell counts, but some patients also ex­peri­enced severe weakness. Other common side effects in­cluded gastro­in­tes­ti­nal issues, nausea, fatigue, fever, dizzi­ness, res­pira­tory issues, and periph­eral neu­rop­athy (pain and tingling in the extremities).

The other panobinostat poster highlighted a large Phase 3 clin­i­cal trial that is still in progress (abstract).  The trial is fur­ther studying whether the addi­tion of panobinostat im­proves the ef­fi­cacy of Velcade plus dexa­meth­a­sone. The in­ves­ti­ga­tors are still looking to en­roll another 270 re­lapsed / re­frac­tory myeloma patients who have re­ceived one to three prior ther­a­pies.  For more in­­for­ma­tion, see the clinical trial description.

There was also another poster highlighting an on­go­ing Phase 3 clin­i­cal trial.  This one is studying whether the addi­tion of carfilzomib, a new agent being devel­oped by Onyx Pharma­ceu­ticals, im­proves the ef­fi­cacy of Revlimid and dexa­meth­a­sone in re­lapsed myeloma (abstract). This com­bi­na­tion is of par­tic­u­lar interest because Velcade-Revlimid-dexamethasone is extremely ef­fec­tive; how­ever, some patients have dif­fi­culty tolerating the periph­eral neu­rop­athy that can accompany Velcade ther­apy. Carfilzomib, which works similarly to Velcade, appears to be more tol­er­able. The study in­ves­ti­ga­tors are still looking to en­roll another 550 re­lapsed / re­frac­tory myeloma patients who have re­ceived one to three prior ther­a­pies.  For more in­­for­ma­tion, see the clinical trial description.

There was also a poster on the topic of Revlimid and sec­ond­ary cancers, a topic that was discussed in detail during the pre­vi­ous day of the meeting (see re­lated Beacon news).  The study pre­sented during the poster session was an analysis of 11 Celgene-sponsored stud­ies in which re­lapsed / re­frac­tory myeloma patients were treated with Revlimid or Revlimid plus dexa­meth­a­sone (abstract).

Among the 3,839 patients in­cluded in the analysis, 57 cases of sec­ond­ary cancers were reported.  Taking into account how long the patients were treated or followed, 2.08 per­cent of them devel­oped a sec­ond­ary cancer each year.  The rate of patients devel­op­ing sec­ond­ary cancers was similar re­gard­less of length of time on ther­apy; how­ever, there appeared to be a slight trend to­ward higher risk with longer ther­apy.  The risk was also slightly, but not sig­nif­i­cantly, higher for patients who had undergone a prior stem cell trans­plant.

After a median follow-up of almost five years, 4 per­cent of par­tic­i­pants had devel­oped a sec­ond blood-related cancer, 10 per­cent devel­oped a solid tumor, and 24 per­cent died, showing that myeloma patients are at greater risk of dying from myeloma or other causes than devel­op­ing a sec­ond cancer. At three years, the over­all sur­vival was similar be­tween patients who devel­oped a sec­ond­ary cancer and those who did not.

The study in­ves­ti­ga­tors concluded that the ben­e­fit-risk profile for Revlimid ther­apy remains strongly pos­i­tive but that there are a num­ber of lim­i­ta­tions to the ways in which sec­ond­ary cancers are tracked that may have affected their analysis.

Further details about Monday’s sessions are avail­able in The Myeloma Beacon’s extensive Day 4 coverage in the Beacon multiple myeloma forums.  Addi­tional coverage of key re­search re­­sults from the meeting will con­tinue throughout the rest of the week in in­di­vid­ual, topic-specific news articles.  For all Beacon articles re­lated to this year’s ASCO meeting, see The Beacon’s full ASCO 2011 coverage.

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