ASCO 2014 Multiple Myeloma Update – Day One
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, Revlimid (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).
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 (abstract; poster [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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- Lather, Rinse, Repeat: Will It Work With BCMA-Targeted Therapies For Multiple Myeloma?
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
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.
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
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.
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