ASH 2012 Multiple Myeloma Update – Day Two: Late Afternoon Oral Session
Published: Dec 10, 2012 5:40 am; Updated: Dec 16, 2012 6:40 pm


Yesterday was the second day of the 2012 American Society of Hematology (ASH) annual meeting, which is being held in Atlanta.
The day's myeloma-related presentations began in the afternoon with three sessions of oral presentations. Two of the sessions focused on results from clinical trials, most of which studied drugs that are still being developed for the treatment of multiple myeloma. The third session, which focused on the biology of myeloma, ran simultaneously with one of the sessions about clinical trial results.
An update published yesterday evening summarized the results for the first oral session about multiple myeloma treatments (see related Beacon news). This article will summarize the highlights from the second oral session about myeloma treatments.
The second session kicked off with two presentations involving treatment regimens that include maintenance therapy with thalidomide. These results are likely to be of primary interest to Beacon readers outside of the U.S., where thalidomide maintenance therapy is used much more frequently than in the U.S.
Three of the presentations from the late afternoon session concerned new myeloma therapies still under development. The presentations about pomalidomide and elotuzumab made clear why there is significant interest in those drugs. Results for the third drug in the group, oprozomib, were based on a trial that currently has only a small number of patients; the results, however, suggest that side effects may be an issue with the drug.
Thalidomide Maintenance
Dr. Annamaria Brioli from the Institute of Cancer Research in London presented the results from a study comparing thalidomide (Thalomid) maintenance therapy versus no maintenance therapy (abstract). The results were part of a larger study which has been reported about extensively in the past.
The study included 818 multiple myeloma patients of whom 408 received thalidomide maintenance therapy and 410 received a placebo.
The median progression-free survival time was 23 months for those in the thalidomide maintenance group and 15 months for those who received a placebo. The median overall survival times were 59 months and 58 months, respectively.
Dr. Brioli then reported that standard-risk patients who received thalidomide maintenance had significantly longer progression-free survival than those who received no maintenance (30 months and 20 months, respectively). High-risk patients had similar progression-free survival regardless of whether they received maintenance therapy (11 months and 13 months, respectively), but their overall survival was negatively affected if they received thalidomide maintenance therapy (35 months versus not yet reached). Patients classified as ultra-high risk had poor progression-free and overall survival, regardless of whether they received maintenance therapy.
Thalidomide maintenance appeared to improve progression-free survival of patients who did not have the chromosomal abnormality t(4;14) or who had t(4;14) but no additional chromosomal abnormalities.
Patients with one or more extra chromosomes also appeared to gain a progression-free survival benefit from thalidomide maintenance.
VMPT-VT Versus VMP
The second presentation was given by Dr. Antonio Palumbo from the University of Torino in Italy. Dr. Palumbo presented four-year survival results from a Phase 3 study comparing two Velcade-based regimens (abstract; presentation slide deck made available by Dr. Palumbo as a courtesy to the Beacon's readers).
The study included 511 newly diagnosed multiple myeloma patients with a median age of 71 years.
Half of the patients received initial therapy with Velcade (bortezomib), melphalan (Alkeran), prednisone, and thalidomide followed by maintenance therapy with Velcade and thalidomide, known as VMPT-VT. The other half received only initial therapy with Velcade, melphalan, and prednisone, known as VMP.
After a median follow-up of nearly four years, the median overall survival of the VMPT-VT group was not yet reached, as compared to 61 months for the VMP group.
Dr. Palumbo estimated that five years after the start of treatment, 61 percent of the VMPT-VT group would be alive, as compared to 51 percent of the VMP group. He noted that patients younger than 75 years of age and patients who achieved a complete response after their initial therapy benefitted the most from the VMPT-VT therapy.
Among those who received maintenance therapy, the most common severe side effects were peripheral neuropathy (4 percent), blood-related side effects (3 percent), and infection (1 percent).
Pomalidomide Plus Dexamethasone
The next three presentations were about new drugs being developed for the treatment of multiple myeloma. First, Dr. Martha Lacy from the Mayo Clinic in Rochester, Minnesota, presented long-term follow-up results from six Phase 2 studies of pomalidomide plus dexamethasone (Decadron) (abstract; presentation slide deck (pdf) made available by Dr. Lacy as a courtesy to the Beacon's readers).
Pomalidomide is an immunomodulatory agent, meaning that it works by inducing a patient’s immune system to attack and destroy myeloma cells. It belongs to the same class of drugs as thalidomide (Thalomid) and Revlimid (lenalidomide).
Pomalidomide is being developed by Celgene Corporation (NASDAQ: CELG), the same company that markets Revlimid and thalidomide in the United States and internationally.
The studies included 344 myeloma patients who were a median of 4.4 years from their myeloma diagnosis and who had been treated with a median of three prior therapies. The median patient age was 64 years.
Overall, 35 percent of patients responded to the treatment, with 5 percent achieving a complete response, 12 a very good partial response, and 18 a partial response. The strongest predictor or response was the number and type of previous therapies.
After a median follow-up of 10.4 months, 62 percent of patients are alive and 30 percent have not yet progressed. The strongest predictor for time to progression and survival were the number and type of previous therapies, LDH levels and beta-2 microglobulin levels.
Severe side effects included low white blood cell counts (50 percent), low red blood cell counts (17 percent), low platelet counts (13 percent), pneumonia (9 percent), and fatigue (8 percent). In addition, 3 percent of patients developed blood clots in the vein.
Elotuzumab Plus Revlimid And Dexamethasone
Next, Dr. Paul Richardson from the Dana-Farber Cancer Institute in Boston presented results from a Phase 2 study of elotuzumab in combination with Revlimid and dexamethasone (abstract; presentation slide deck made available by Dr. Richardson as a courtesy to the Beacon's readers).
Elotuzumab, which is being developed by Bristol-Myers Squibb (NYSE: BMY) and Abbott (NYSE: ABT), belongs to a class of drugs called monoclonal antibodies. Monoclonal antibodies work by identifying proteins on the surface of myeloma cells and signaling for the immune system to destroy the cancer cells. Other compounds in this class of drugs include daratumumab and siltuximab, which are in earlier phases of clinical development than elotuzumab.
The study included 73 myeloma patients treated with a median of two prior lines of therapy. The median patient age was 63 years.
Half of the study participants received 10 mg/kg of elotuzumab, while the other half received 20 mg/kg of the drug.
The results showed that the outcomes of those treated with 10 mg/kg of elotuzumab were better than the outcomes of those treated with 20 mg/kg.
In particular, 92 percent of the patients in the 10 mg/kg group responded to treatment, as compared to 76 percent in the 20 mg/kg group.
After a median follow-up of 21 months, median progression-free survival has not been reached yet for the 10 mg/kg group and 19 months for the 20 mg/kg group.
Two-thirds of the patients experienced at least one severe or life-threatening side effect. The most common were low blood cell counts (10 percent to 20 percent).
The combination using 10 mg/kg of elotuzumab is being further studied in Phase 3 studies of newly diagnosed myeloma patients.
Oprozomib
Dr. Michael Savona from the Sarah Cannon Research Institute in Nashville, Tennessee, then discussed results of a Phase 1b study of oprozomib (abstract).
Oprozomib is being developed by Onyx Pharmaceuticals (NASDAQ: ONXX), the company that markets Kyprolis (carfilzomib).
Oprozomib is chemically very similar to Kyprolis, and also works similarly to Velcade. All three of these drugs belong to the class of drugs known as proteasome inhibitors. They work by preventing the breakdown of protein in cancer cells, triggering their death. Oprozomib, unlike Kyprolis and Velcade, can be taken orally.
Oprozomib is currently being investigated as a treatment for solid tumors as well as blood cancers.
Dr. Savona presented initial results from 13 people with blood cancers who received between 120 mg and 210 mg of oprozomib per day. The study participants had received a median of four previous treatment regimens.
Of the 10 patients evaluated for response, nine achieved at least stable disease. Two patients with multiple myeloma achieved a partial response and a minimal response. An additional patient with chronic lymphocytic leukemia achieved a partial response.
The most common side effects were diarrhea (78 percent), nausea (78 percent), and vomiting (67 percent).
Myeloma presentations from the rest of Day 2 as well as Day 3 and Day 4 of the ASH 2012 meeting also will be summarized in ASH daily updates to be published at The Beacon the next few days. 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 ASH meeting, see The Beacon’s full ASH 2012 coverage.
Related Articles:
- bb2121 Continues To Impress As Potential New Multiple Myeloma Therapy (ASCO 2018)
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Lather, Rinse, Repeat: Will It Work With BCMA-Targeted Therapies For Multiple Myeloma?
- Importance Of Factors Affecting Multiple Myeloma Survival Changes With Patient Age
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma
Hmmmmm
RE: Thalidomide Maintenance,
"High-risk patients had similar progression-free survival regardless of whether they received maintenance therapy (11 months and 13 months, respectively), but their overall survival was negatively affected if they received thalidomide maintenance therapy (35 months versus not yet reached)."
It seems that maintenance therapy with thalidomide does not increase PFS but it does DECREASE OS for high-risk patients.? So, the high risk patients who did not receive thalidomide maintenance had better OS!
A real conundrum.
Re: Pomalidamide plus Dex,
"The strongest predictor for time to progression and survival were the number and type of previous therapies, LDH levels and beta-2 microglobulin levels."
What were the LDH levels and beta-2 microglobulin levels that correlated with longer time to progression and survival? And what number/type of previous therapy correlated with shorter time to progression and survival.
Re: Elotuzumab plus Dex and Rev
"The results showed that the outcomes of those treated with 10 mg/kg of elotuzumab were better than the outcomes of those treated with 20 mg/kg.
In particular, 92 percent of the patients in the 10 mg/kg group responded to treatment, as compared to 76 percent in the 20 mg/kg group."
So less drug was more efficacious? How was this explained in terms of MOA? Why does less of a monoclonal AB work more effectively?. Is this about there being a finite number of receptor sites...hmmm perhaps, not since if all the receptors were saturated, then both doses should be equally effective and not less effective in higher doses.
Is this about patient population variance? Do the myeloma cells vary that much in the patient population? Did the patients in the 10 vs 20 mg/kg arm have fewer prior therapies or different prior therapies from those in the 20mg/kg arm?
I located some of the additional details on Pom/Dex from Mayo:
"Strongest predictors of nonresponse to pomalidomide/dexamethasone included > 3 previous treatment regimens, previous lenalidomide, and prior bortezomib"
β2-microglobulin (> 5.5 vs ≤ 5.5 mg/dL)
and
LDH greater than Upper Limit of Normal (ULN)
http://www.clinicaloptions.com/Oncology/Conference%20Coverage/Hematology%202012/Myeloma/Capsules/201.aspx
This article has been updated with links to presentation slide decks provided by Dr. Lacy and Dr. Palumbo.
This article has been updated with a link to the elotuzumab-Revlimid-dex presentation slide deck that Dr. Richardson discussed during his presentation.
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