This year’s American Society of Clinical Oncology (ASCO) annual meeting began yester­day morning in Chicago and will run through Tuesday.

Myeloma-related pre­sen­ta­tions were made during two sessions yes­ter­day.

One session was designed to better educate physicians about per­son­al­ized ther­apy for elderly patients with lymphoid malig­nan­cies. During that session, Dr. Tanya Marya Wildes from the Washington University School of Medicine in St. Louis talked about how to navigate treat­ment options for older multiple myeloma patients.

The key myeloma-related re­search pre­sented yesterday was made public during a poster session in the afternoon about studies testing new and existing treat­ments for myeloma.

During the session, re­search results were made avail­able for review by meeting attendees in the form of posters, each of which summarized the results of a single study. As is typically the case during such sessions, each poster was about two feet high by three or four feet in length. All posters were dis­played through­out a large conference hall.

This update covers many of the myeloma-related studies pre­sented during yesterday’s poster session.

The next myeloma-related sessions at the ASCO meeting are not scheduled until Monday, when studies results will be pre­sented in an oral session in the morning and a poster session in the afternoon. The Beacon will report about those results in articles to be pub­lished after the sessions have taken place.

Daratumumab

Yesterday's session in­cluded a poster summarizing updated results of a Phase 1/2 trial investigating the com­bi­na­tion of daratumumab ^[1], Revlimid ^[2] (lena­lido­mide), and dexa­metha­sone ^[3] (Decadron) as a treat­ment for re­lapsed myeloma patients (abstract ^[4]; poster ^[5] [pdf]).

Daratumumab is being devel­oped by the Danish bio­technology com­pany Genmab together with Janssen Biotech, a Johnson & Johnson (NYSE: JNJ) sub­sid­i­ary. It is a mono­clonal anti­body, like elotuzumab ^[6] and SAR650984 ^[7]. It works by targeting a protein known as CD38 that is fre­quently found on the surface of myeloma cells.

The trial has recruited 22 patients so far with a median age of 62 years who re­ceived a median of 3 prior ther­a­pies.

Patients re­ceived dara­tu­mu­mab doses ranging from 2 mg/kg to 16 mg/kg in the Phase 1 part of the trial. Since the maximum tolerated dose was not reached, 16 mg/kg is being explored in the Phase 2 part of the trial.

Of the 20 patients evaluable for re­sponse­, 75 per­cent have so far responded to the three-drug treat­ment, with 15 per­cent achieving a com­plete re­sponse­, 45 per­cent a very good partial re­sponse or com­plete re­sponse, and 15 per­cent a partial re­sponse­.

The most common side effects in­cluded low white blood cell counts (32 per­cent), diarrhea (32 per­cent), and fatigue (27 per­cent).

According to the in­ves­ti­ga­tors, this com­bi­na­tion merits further devel­op­ment. They point out that a Phase 3 trial com­par­ing the three-drug com­bi­na­tion to Revlimid-dexamethasone alone has been ini­ti­ated.

SAR650984

Results of a Phase 1 trial testing SAR650984 in heavily pre­treated myeloma patients were also pre­sented during the poster session (abstract ^[8]; poster ^[9] [pdf]).

Initial results of the trial were pre­sented at last year’s annual meeting of the American Society of Hematology (see related Beacon ^[10] news).

SAR650984, which is being devel­oped by the French pharma­ceu­tical com­pany Sanofi, is also a mono­clonal anti­body and targets the same protein as dara­tu­mu­mab.

The study in­cluded 40 heavily pre­treated myeloma patients with a median age of 64 years who had re­ceived a median of seven prior ther­a­pies. All patients had pre­vi­ously re­ceived Velcade ^[11], 93 per­cent had re­ceived pre­vi­ously re­ceived Revlimid, 43 per­cent Kyprolis ^[12] (car­filz­o­mib), and 23 per­cent Pomalyst ^[13] (poma­lido­mide; Imnovid).

The trial explored 12 dif­fer­en­t dose and dosing-frequency com­bi­na­tions of SAR650984, ranging from 0.0001 mg/kg every two weeks to 10 mg/kg every week.   SAR650984 was admin­istered as a single agent, although patients re­ceiv­ing SR650984 doses of 3 mg/kg or higher also re­ceived 100 mg of pred­ni­sone during their SAR650984 in­fusions to prevent in­fusion-related side effects.

Of the 30 patients evaluable for re­sponse­, 33 per­cent of those treated with at least 1 mg/kg of SAR650984 every two weeks responded, and 27 per­cent of those treated with at least 10 mg/kg every two weeks responded.

The maximum tolerated dose of single-agent SAR650984 has not yet been reached during the study.

The most common side effects in­cluded fatigue (53 per­cent), nausea (35 per­cent), fever (28 per­cent), and anemia (28 per­cent).

TH-302

The session also in­cluded a poster summarizing updated results from a Phase 1/2 study of TH-302 ^[14] plus dexa­metha­sone in heavily pre­treated myeloma patients (abstract ^[15]; poster  ^[16][pdf]).

Initial results were pre­sented at last year’s ASCO annual meeting (see related Beacon ^[17] news).

TH-302 is being devel­oped by Threshold Pharma­ceu­ticals (NASDAQ:THLD) and the German pharma­ceut­i­cal com­pany Merck KGaA. TH-302 anti-cancer activity is activated under low oxygen level con­di­tions, which are common in tumors and in the bone mar­row of people with blood cancers. It is cur­rently also being in­ves­ti­gated in a range of solid tumors.

The study so far has enrolled 30 patients. The data summarized in the poster is based on data from 24 patients with a median age of 63 years who had re­ceived a median of seven prior lines of ther­apy. All patients had pre­vi­ously re­ceived Revlimid and Velcade.

The patients were treated with one of three dif­fer­en­t doses of TH-302 plus dexa­meth­a­sone.

Of the 23 patients evaluable for re­sponse­, 17 per­cent achieved a partial re­sponse­, 9 per­cent reached a minimal re­sponse­, and 65 per­cent had stable dis­ease.

The most common severe side effects in­cluded low platelet counts (29 per­cent), low red blood cell counts (25 per­cent), and low leukocytes counts (25 per­cent).

As of May 19, 2014, 17 per­cent of patients remain on treat­ment.

The authors point out that Velcade will be added to the com­bi­na­tion for Phase 2 of the study.

Four-Drug Regimen Involving Kyprolis And Zolinza

Another poster summarized initial results from a Phase 1 trial of a four-drug regi­men for re­lapsed myeloma.  The regi­men in­cludes Kyprolis, Revlimid, Zolinza ^[18] (vorinostat), and dexa­meth­a­sone – a regi­men that trial in­ves­ti­ga­tors have labeled “QUAD” (abstract ^[19]; poster ^[20] [pdf] courtesy of Dr. David Vesole).

The study in­cluded 21 patients with a median age of 61 years who had re­ceived a median of three prior lines of ther­a­pies. All patients had pre­vi­ously re­ceived a stem cell trans­plant, 95 per­cent had re­ceived Revlimid, 95 per­cent had re­ceived Velcade, and 25 per­cent had re­ceived Zolinza.

Of the 17 patients evaluable for re­sponse­, 53 per­cent responded, with 12 per­cent achieving a very good partial re­sponse­ and 41 per­cent a partial re­sponse­.

At a median follow-up of 6.5 months, the median pro­gres­sion-free sur­vival was 12 months, and the median over­all sur­vival has not been reached yet.

The most common severe side effects were low white blood cell counts (43 per­cent), low platelet counts (43 per­cent), and low red blood cell counts (33 per­cent).

CRD versus CTD

Results of a large U.K. Phase 3 trial were also dis­played during yesterday’s poster session (abstract ^[21]).

The so-called Myeloma XI trial thus far in­cludes nearly 2,000 newly diag­nosed multiple myeloma patients.  Par­tic­i­pants in the trial re­ceived initial treat­ment with either cyclophosphamide ^[22] (Cytoxan), Revlimid, and dexa­meth­a­sone (CRD), or cyclo­phos­pha­mide, thalido­mide, and dexa­meth­a­sone (CTD).

The results show that patients in the trial who have re­ceived the Revlimid-containing regi­men (CRD) have had deeper re­sponse­s than patients who have re­ceived the thalido­mide-containing regi­men (CTD).

Specifically, 25 per­cent of patients on CRD achieved a com­plete re­sponse­, 30 per­cent a very good partial re­sponse­, and 26 per­cent a partial re­sponse­, com­pared to 15 per­cent who achieved a com­plete re­sponse­ on CTD, 33 per­cent a very good partial re­sponse­, and 31 per­cent a partial re­sponse­ on CTD.

Overall re­sponse­ rates for the two regi­mens, how­ever, were similar.

The in­ves­ti­ga­tors point out that further follow-up is nec­es­sary to see if dif­fer­ence in re­sponse­ rates will affect pro­gres­sion-free and over­all sur­vival.

Patients who re­ceived CRD had lower rates of mod­er­ate to severe periph­eral neu­rop­athy 1.9 per­cent) com­pared to patients who re­ceived CTD (6.3 per­cent). However the rates of severe blood-related side effects were higher among patients who re­ceived CRD com­pared to those who re­ceived CTD.

Busulfan Plus Melphalan Versus Melphalan Alone

The session also in­cluded a poster pre­sen­ta­tion with results of a Phase 3 trial com­par­ing two dif­fer­en­t high-dose chemo­ther­apy regi­mens for use during au­tol­o­gous (own) stem cell trans­plan­ta­tion in myeloma pa­tients (abstract ^[23]; poster ^[24] [pdf] and addi­tional explanatory slides ^[25] [PDF], both courtesy of Dr. Muzaffar Qazilbash).

One group of patients in the study re­ceived a com­bi­na­tion of busulfan ^[26] (Busulfex) and melphalan ^[27] (Alkeran), spread out over several days, as their high-dose chemo­ther­apy prior to trans­plan­ta­tion.  The other group re­ceived a standard dose of mel­phalan as high-dose chemo­ther­apy.

Ninety days post trans­plant, the over­all re­sponse­ rate was the same be­tween the two treat­ment groups (97 per­cent). However, the share of patients who achieved a com­plete re­sponse­ was noticeably higher among patients who re­ceived standard mel­phalan (35 per­cent) than among patients who re­ceived the busulfan-melphalan com­bi­na­tion (18 per­cent).

However, the busulfan-melphalan com­bi­na­tion led to a somewhat higher one-year pro­gres­sion-free sur­vival (93 per­cent), com­pared to standard mel­phalan (82 per­cent).

Standard mel­phalan, on the other hand, was asso­ci­ated with a sig­nif­i­cantly lower rate of severe non-blood related side effects (47 per­cent) than the busulfan-melphalan com­bi­na­tion (83 per­cent).

The re­searchers point out that a longer follow-up is needed to eval­u­ate the impact of the busulfan-melphalan com­bi­na­tion on pro­gres­sion-free sur­vival.

Effect Of Cereblon-Binding Proteins On Outcomes After Pomalyst Therapy

Another poster pre­sented during yesterday’s session summarized the findings of a study conducted at the Mayo Clinic showing that cer­tain cereblon-binding proteins may be bio­­markers that predict re­sponse­ and sur­vival after Pomalyst (poma­lido­mide, Imnovid) ther­apy (abstract ^[28]; poster ^[29] [pdf] courtesy of Drs. Yuan Xiao Zhu and Martin Kortum).

Cereblon is a protein that has been shown to affect re­sponse­ rates and sur­vival in multiple myeloma patients treated with the immuno­modu­la­tory agents Revlimid, thalido­mide, and Pomalyst (see related Beacon ^[30] news).

Specifically, the re­searchers found that more patients with high levels of ikaros transcription factor (IKZF) 1 (39 per­cent) responded to treat­ment with Pomalyst and dexa­meth­a­sone, com­pared to patients with low levels of IKZF1 (6 per­cent).

Patients with high levels of IKZF1 also had sig­nif­i­cantly longer pro­gres­sion-free sur­vival 13 months, com­pared to patients with low levels (3 months).

The median over­all sur­vival was also the longest for patients with the highest IZKF1 levels (47 months) and shortest for patients with the lowest levels (7.2 months).

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Myeloma pre­sen­ta­tions from Day 4 of the ASCO meeting will also be summarized in Beacon ASCO daily updates to be pub­lished next week.  Additional coverage of key re­search results from the meeting will con­tinue after the meeting is over with in­di­vid­ual, topic-specific news articles.  For all Beacon articles related to this year’s ASCO meeting, see The Beacon’s full ASCO 2014 ^[31] coverage.