Yesterday was the third day of the American Society of Clinical Oncology (ASCO) 2011 annual meeting in Chicago, and it was especially packed with pre­sen­ta­tions re­lated to mul­ti­ple myeloma.

There was a morn­ing session where a total of eight re­search abstracts were pre­sented and discussed.  Then, late in the afternoon, there was an education session focused on mul­ti­ple myeloma, with sev­er­al dif­fer­en­t pre­sen­ta­tions.

The pre­sen­ta­tions during the morn­ing session were on three dif­fer­en­t topics: Revlimid ^[1] (lena­lido­mide) and its po­ten­tial link to sec­ond­ary cancer; myeloma bone dis­ease; and new drugs being devel­oped as po­ten­tial treat­ments for mul­ti­ple myeloma.

This article will summarize the ma­teri­al re­lated to two of the morn­ing session’s three topics – Revlimid and sec­ond­ary cancer, and po­ten­tial new myeloma treat­ments – while the sec­ond part of The Beacon's up­date for Day Three will summarize the rest of the day’s myeloma-related pre­sen­ta­tions.

The morn­ing oral session started off with the pre­sen­ta­tions on Revlimid and sec­ond­ary cancer.  The first of those pre­sen­ta­tions was by Dr. Antonio Palumbo of the Uni­ver­sity of Torino in Italy.  He spoke about sec­ond­ary cancers in the Revlimid main­te­nance study (MM-015) for which he is the lead in­ves­ti­ga­tor.  The trial in­volves newly diag­nosed elderly myeloma patients who are not eli­gible for a stem cell trans­plant.

A third of the patients in the MM-015 trial were treated with melphalan ^[2] (Alkeran) and prednisone ^[3] (MP), a third also re­ceived Revlimid at the same time (MPR), and the final third re­ceived the three-drug com­bi­na­tion followed by long-term Revlimid main­te­nance ther­apy (MPR-R).

As of Feb­ru­ary 28, there were four reported cases of sec­ond­ary cancers in the MP group, nine in the MPR group, and 12 in the MPR-R group. All patients who had complex cytogenetics (chromosomal ab­nor­mal­i­ties) were in the MPR and MPR-R groups. These patients were at sig­nif­i­cantly higher risk of devel­op­ing a sec­ond­ary cancer, which may ex­plain, at least in part, the discrepancies in sec­ond­ary cancers in the three treat­ment groups.

Dr. Palumbo analyzed the rel­a­tive risk of devel­op­ing a sec­ond­ary cancer versus dis­ease pro­gres­sion or death and concluded that the ben­e­fit-risk ratio for Revlimid was fa­vor­able.  This was con­firmed, in Dr. Palumbo’s opinion, by addi­tional re­search he did looking retro­spec­tively at the re­­sults of nine other mul­ti­ple myeloma clin­i­cal trials.

Dr. Adrianna Rossi from the Weill Cornell Medical College and New York Presbyterian Hospital spoke next about sec­ond­ary malig­nan­cies after six years of follow-up in 72 newly diag­nosed myeloma patients treated with clarithromycin (Biaxin), Revlimid, and dexamethasone ^[4] (Decadron) – known as BiRD.

The regi­men was very ef­fec­tive, with an over­all re­sponse rate of 90 per­cent. Sixteen per­cent of the par­tic­i­pants devel­oped a sec­ond cancer after an average of 31 cycles of Revlimid. The sec­ond­ary cancers were not asso­ci­ated with spe­cif­ic chromosomal ab­nor­mal­i­ties, whether or not the patient re­ceived a stem cell trans­plant, whether or not the patient was still on Revlimid, or patient gender. The frequency of sec­ond­ary cancers in this study (2.85 per­cent per patient year) was similar to cancer rates in in­di­vid­uals of similar age who do not have myeloma (2.1 per­cent per patient year).

Dr. Ruben Niesvizky from Weill Cornell Medical College then spoke about sec­ond­ary cancers in two trials in which re­lapsed / re­frac­tory myeloma patients were treated with Revlimid and dexa­meth­a­sone or dexa­meth­a­sone alone until dis­ease pro­gres­sion.

With a median follow-up time of 48 months, eight sec­ond­ary cancers were reported in the Revlimid-dexamethasone arm, com­pared to two sec­ond­ary cancers for the dexa­meth­a­sone-alone arm.  Time to pro­gres­sion or de­vel­op­ment of a sec­ond cancer was 12.4 months for Revlimid-dexamethasone versus 4.6 months for dexa­meth­a­sone alone.

Taking into account that Revlimid plus dexa­meth­a­sone sig­nif­i­cantly extended sur­vival (overall sur­vival of 31 months com­pared to 24 months) and that older ages are asso­ci­ated with a higher risk of cancer, the observed sec­ond­ary cancer rates in both treat­ment arms were com­parable to ex­pected rates based on the general pop­u­la­tion.  Based on his analysis, Dr. Niesvizky concluded that the ben­e­fit-risk ratio for Revlimid remains strongly pos­i­tive.

The section of the morn­ing session on Revlimid and sec­ond­ary cancer was concluded by a summary dis­cus­sion led by Dr. Ola Landgren from the National Cancer In­sti­tute. Dr. Landgren reviewed sev­er­al stud­ies from over the years that showed that a num­ber of myeloma patients have devel­oped sec­ond­ary cancer after being treated with mel­phalan. He then talked about the three large Revlimid main­te­nance stud­ies (CALGB 100104, IFM 2005-02, and MM-015) that have all shown a higher rate of sec­ond­ary cancers in the Revlimid arms. Despite patients in the Revlimid arms having a higher risk of devel­op­ing a sec­ond cancer, over­all sur­vival in one of these stud­ies (CALGB 100104) was sig­nif­i­cantly longer for the Revlimid group than the placebo group. Dr. Landgren stressed the need to under­stand the mech­a­nisms causing these sec­ond cancers and to be able to identify which myeloma patients are most likely to de­vel­op a sec­ond cancer.

Later in yes­ter­day’s morn­ing session, there was a series of pre­sen­ta­tions on clin­i­cal trial re­­sults for sev­er­al po­ten­tial new myeloma treat­ments.

Dr. Noopur Raje from the Dana-Farber Cancer In­sti­tute in Boston began this section of the session with a pre­sen­ta­tion of re­­sults from a Phase 1 study of LY2127399 and Velcade ^[5] (bor­tez­o­mib) in patients with pre­vi­ously treated myeloma.

LY2127399 is being devel­oped by the U.S. pharma­ceu­tical com­pany Eli Lilly.  It is a human anti­body that targets a pro­tein called BAFF, which is present in the myeloma cells of about 60 per­cent of myeloma patients. The pri­mary goal of this study was to identify the best dosing for LY2127399 in com­bi­na­tion with Velcade.

The study in­cluded 20 patients with a median of three prior ther­a­pies. Median time to pro­gres­sion was 4.9 months. All doses were well tol­er­ated, and side effects were similar to Velcade alone. There were a few cases each of severe low blood cell counts, diarrhea, and periph­eral neu­rop­athy. However, three patients dis­con­tinued ther­apy due to neu­rop­athy. The over­all re­sponse rate was 55 per­cent. Prior Velcade ther­apy did not affect re­sponse.

The next talk was given by Dr. Jesus Berdeja from the Sarah Cannon Re­search In­sti­tute in Nashville, Tennessee. Dr. Berdeja pre­sented initial re­­sults from an on­go­ing Phase 1 study of lorvotuzumab mertansine ^[6] (LM, or IMGN901) in com­bi­na­tion with Revlimid and dexa­meth­a­sone in a spe­cif­ic subset of re­lapsed / re­frac­tory myeloma patients whose myeloma cells con­tain the CD56 pro­tein.

LM, which is being devel­oped by the U.S. bio­tech com­pany ImmunoGen, is a chemo­ther­apy drug (mertansine) chemically tied to an anti­body (lorvotuzumab) that directs LM to cells with the CD56 pro­tein. About 70 per­cent of myeloma patients have myeloma cells with CD56; the pro­tein is not found in nor­mal plasma cells.

Sixteen patients were en­rolled in the LM trial at the time the analysis for Dr. Berdeja’s pre­sen­ta­tion was carried out.  So far, the over­all re­sponse has been 62 per­cent. Dr. Berdeja also said that lorvotuzumab was active in patients with un­fa­vor­able chromosomal mutations. Addi­tionally, lorvotuzumab appears to be well tol­er­ated. The main severe side effect was periph­eral neu­rop­athy.

Dr. Philippe Moreau from the Uni­ver­sity Hospital in Nantes, France, pre­sented the final pre­sen­ta­tion on po­ten­tial new myeloma treat­ments.  He pre­sented re­­sults from a Phase 2 study of elotuzumab ^[7] in com­bi­na­tion with Revlimid and low-dose dexa­meth­a­sone in patients with re­lapsed myeloma.

Elotuzumab is being devel­oped by Bristol-Myers Squibb.  The drug is an anti­body that targets myeloma cells. The study discussed by Dr. Moreau in­cluded 63 patients, and two dif­fer­en­t doses of elotuzumab were tested. The over­all re­sponse rate across both doses was 82 per­cent.  Progression-free sur­vival was not yet reached at a median follow-up of 9 months. The only severe side effects were low blood cell counts due to Revlimid. The most common side effects were in­fusion reac­tions that in­cluded nausea, dizzi­ness, headache, and fever.

Dr. Moreau concluded from the initial re­­sults from this trial that elotuzumab plus Revlimid and dexa­meth­a­sone appears to be superior to Revlimid and dexa­meth­a­sone alone. Based on data showing that the over­all re­sponse rate was 90 per­cent in patients with only one prior ther­apy, Dr. Moreau sug­gested that this com­bi­na­tion should also be tested earlier in the dis­ease course.

The three pre­sen­ta­tions about po­ten­tial new myeloma treat­ments were followed by a summary dis­cus­sion led by Dr. Nikhil Munshi from the Dana-Farber Cancer In­sti­tute.

Dr. Munshi started off by saying that there are more than 10 mono­clonal anti­bodies in dif­fer­en­t stages of clin­i­cal testing as po­ten­tial new myeloma treat­ments.  However, the single-agent anti-myeloma ac­­tiv­ity of these drugs has been modest to date. He said that com­bi­na­tion ap­proaches are there­fore likely to be re­quired.

In regard to both LY2127399 and LM, Dr. Munshi felt that the re­­sults pre­sented during the session were fa­vor­able, but that more evi­dence is needed before the two drugs can be categorized as promising anti-myeloma agents.

Dr. Munshi was more fa­vor­able about the pros­pects for elotuzumab.  Although he feels there are still im­por­tant unanswered questions in regard to the drug, he con­siders the com­bi­na­tion of elotuzumab and Revlimid to be promising.

As part of its coverage of the 2011 ASCO meeting, The Beacon will be pub­lishing more com­plete reviews of each of the new drug pre­sen­ta­tions from yes­ter­day’s morn­ing session as well as an addi­tional article focused on the morn­ing’s pre­sen­ta­tions about Revlimid and sec­ond­ary cancer.

Further details of yes­ter­day’s sessions also are avail­able in The Myeloma Beacon’s extensive Day 3 ^[8] coverage in the Beacon multiple myeloma forums ^[9].  News from the rest of the ASCO meeting will likewise be summarized in the forums and in other daily up­dates like this one.