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ASCO 2014 Multiple Myeloma Update – Day One

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Published: May 31, 2014 9:17 pm

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 daratumumabRevlimid (lena­lido­mide), and dexa­metha­sone (Decadron) as a treat­ment for re­lapsed myeloma patients (abstract; poster [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 and SAR650984. 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; poster [pdf]).

Initial results of the trial were pre­sented at last year’s annual meeting of the American Society of Hematology (see related Beacon 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, 93 per­cent had re­ceived pre­vi­ously re­ceived Revlimid, 43 per­cent Kyprolis (car­filz­o­mib), and 23 per­cent Pomalyst (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 plus dexa­metha­sone in heavily pre­treated myeloma patients (abstractposter [pdf]).

Initial results were pre­sented at last year’s ASCO annual meeting (see related Beacon 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 (vorinostat), and dexa­meth­a­sone – a regi­men that trial in­ves­ti­ga­tors have labeled “QUAD” (abstract; poster [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).

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 (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; poster [pdf] and addi­tional explanatory slides [PDF], both courtesy of Dr. Muzaffar Qazilbash).

One group of patients in the study re­ceived a com­bi­na­tion of busulfan (Busulfex) and melphalan (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; poster [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 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 coverage.

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3 Comments »

  • Myeloma Beacon Staff said:

    For those new to reading about myeloma-related research, this set of 'Tips for Making Sense of Myeloma Research Results,' published by the Beacon before the 2012 ASH annual meeting, may be worth a quick read.

  • carola sprague said:

    My husband Stuart S. Sprague (born 6/24/37) was diagnosed with multiple myeloma in August 1993, at the age of 56; he died of MM on February 22, 2002 at age 64.

    In August 1993, a tumor appeared on his spine which finally led to the MM diagnosis, after he experienced "crippling" problems that summer which had him crawling instead of walking. It took eastern Kentucky doctors three months that summer to finally diagnose his problem as MM - surgery to remove the tumor was done, and he appreciated his no-pain again state of health afterwards.

    He took radiation treatments for about 3 or 4 months, and was essentially MM free for four years. Then, it appeared again, and he was started on oral chemo. He survived another four years on the oral chemo; three years into that process he was hospitalized for ten days to take an infusion of stronger chemo; he weakened, felt awful, and he made the decision to be released from the hospital and back home again taking oral chemo. He lived another 15 months, and enjoyed driving to the library each day since he was a professor by profession, as well as a historian, librarian, author by avocation as well as profession.

    My question to you is: Would he have had a longer lifespan possibly, had the same MM chronology happened ten years later. He died twelve years ago - we appreciated his 8 1/2 years of living with MM, but with the research done in the ten years following his death and currently, would his prognosis been perhaps greater?

    I don't follow MM research, tho' obviously I did today, and just wonder if MM patients these days can look forward to a longer lifespan? Do you follow patients who wish to receive very conservative treatment - i.e. oral chemo only or no chemo - radiation ok, surgery of tumors ok? Has any substantial progress been made in the past 10-12 years since my husband's death??

    Please keep your explanation as simple as possible, and thank you.

    Carola Sprague

    44 Oakdale Ct.
    Clearfield, KY 40313 (3 miles from Morehead in eastern Kentucky

  • Myeloma Beacon Staff said:

    Thank you for your comment, Carola, and for your description of your husband's multiple myeloma diagnosis and later treatment. We are glad to hear that he survived more than seven years after his diagnosis, but saddened that he did not live even longer.

    Since the time when your husband was diagnosed, there have been a number of new medications approved by the FDA to treat multiple myeloma. These medications have helped lengthen the survival of myeloma patients noticeably over the past 20 years.

    When your husband was diagnosed, doctors were telling many myeloma patients like him that they could expect to live perhaps 3 or 4 years after diagnosis. Now, many patients are being given estimates that are at least twice that length of time.

    It still is the case, however, that each myeloma patient has a very individual form of the disease, and looking at the statistics about the disease can cause one to forget that. We have heard of myeloma patients who were diagnosed at the same time as your husband who are still alive today. We also know of myeloma patients diagnosed just several years ago, but who had aggressive forms of the disease that took them from us in just a few years.

    So, yes, the treatment for myeloma has improved quite a bit in the last 20 years. There is still much room for improvement, however, and far too many cases where the disease is still a challenge even with all the medicines we now have at our disposal.

    If you would like to read more about improvements in the survival of myeloma patients over the past 10 to 20 years, here are a few articles that may interest you:

    "Multiple Myeloma Survival Increased Significantly The Past 15 Years, But Unevenly Across Ethnic And Age Groups," The Myeloma Beacon, August 31, 2014.

    "Multiple myeloma survival in 2014," Myeloma Beacon forum discussion started May 22, 2014.