Researchers Determine Outcomes For Myeloma Patients Who Have Failed To Respond To Novel Agent Therapies
A group of international researchers analyzed the outcomes of multiple myeloma patients after they failed to respond to therapy with novel agents, such as Velcade, Revlimid, and thalidomide.
The study authors stated that the results will help physicians and patients better understand patients’ prognoses and select appropriate clinical trials.
“The study provides an estimate of the expected outcome among patients with myeloma that has stopped responding to the newly available drugs,” said Dr. Shaji Kumar from the Mayo Clinic in Minnesota and lead author of the study. “This will allow patients to compare available options and specifically evaluate clinical trial options.”
Since multiple myeloma remains incurable, the researchers involved with this study explained that it is important to be able to determine which treatments in early phases of clinical development are the most promising.
Most treatments under clinical development are first tested in relapsed and refractory (resistant) myeloma patients. To better understand which of these treatments are the most promising, the researchers argued that it would be useful to better understand what treatments patients receive after they fail on current novel agents and how they respond to those treatments. They explained that these results could then be used as a benchmark against which the results for treatments under development could be compared to identify the most promising ones. For example, treatments under development with results inferior to the benchmark would no longer be considered promising.
The researchers, who were part of the International Myeloma Working Group, an international group of top myeloma experts, therefore, retrospectively studied medical records of 286 patients from the United States, Europe, and Asia, who did not respond to Velcade (bortezomib) and also relapsed on, did not respond to, or were unable to take Revlimid (lenalidomide) or thalidomide (Thalomid). The researchers analyzed the records to identify the therapies that were used after the patients failed novel agent therapy as well as response and survival rates for these patients.
The researchers found that 74 percent of patients included in the study continued to receive treatment after becoming non-responsive to novel agents. For the first treatment regimen used after novel agent failure, 26 percent of regimens included Velcade, 19 percent included Revlimid, and 14 percent included thalidomide.
Dr. Kumar explained that a fraction of patients continued to receive novel agent therapy after having failed on these therapies because patients sometimes respond to combinations of these drugs, for example Velcade plus Revlimid, even after failing to respond to individual novel agents.
Response rates to this first regimen included 2 percent complete response, 5 percent very good partial response, and 17 percent partial response. Additionally, overall response rates were the same for patients who received a novel agent-based regimen and those who did not receive a novel agent.
Of the patients who received two or more different treatment regimens after initially failing on novel agents, 35 percent received Velcade, 30 percent received Revlimid, and 24 percent received thalidomide. Additionally, 15 percent of patients received a stem cell transplant after failing novel agent therapy.
Overall response rates were 19 percent after two regimens, 24 percent after three regimens, 22 percent after four regimens, and 6 percent after five regimens following failure to respond to novel agents.
Dr. Kumar said that after patients fail on novel agent therapy, they are most likely to respond to older drugs, such as melphalan (Alkeran), cyclophosphamide (Cytoxan), and doxorubicin (Adriamycin), especially when used in combination with some of the newer drugs.
The median event-free survival was five months and the median overall survival was nine months once patients failed to respond to novel agents. Patients who received treatment after becoming non-responsive had a median overall survival of 12 months, while patients who did not receive further treatment had a median overall survival of three months.
Median overall survival was 11 months from the time patients failed Velcade therapy. Median overall survival was 22 months from the time patients relapsed on, failed, or were unable to tolerate Revlimid and 16 months for thalidomide.
The researchers also determined that high beta-2 microglobulin and low albumin levels in the blood after failing novel agent therapy were strong predictors of poor overall survival.
For more information, please see the article in Leukemia (abstract).
Related Articles:
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
- Adding Clarithromycin To Velcade-Based Myeloma Treatment Regimen Fails To Increase Efficacy While Markedly Increasing Side Effects
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Sustained Complete Response To Initial Treatment Associated With Substantial Survival Benefit In Multiple Myeloma
Hi Lori,
Thanks for sharing your thoughts.
It is indeed a shame when patients are denied treatment that their physicians decide are the best option for them.
Although we are all hoping for better outcomes for all myeloma patients, this study informs patients about response rates and survival times that they might expect after failing novel agent therapy. These are patients who have typically relapsed or been refractory to multiple different therapies several years after diagnosis.
The study indicates that it is important to continue therapy even after failing novel agent therapy. Survival rates were 1 year in patients who continued therapy, but only 3 months for those who discontinued therapy. It also provides a small amount of insight into what therapies may be most effective after failing novel agent therapy (older chemotherapies in combination with novel agents), although not much detail was provided about this.
Also, as researchers try to find better treatments for myeloma patients, particularly those with shorter survival times (relapsed and refractory patients), the results of this study will help researchers determine which treatments under clinical development are the most promising. Those that extend survival times beyond the times found in this study will be ones to certainly pursue further in clinical development.
The study did not stratify patients into risk-groups or analyze outcomes based on chromosomal abnormalities.
I was just informed that a High Risk MM patient has been denied a SCT by the insurance company because his prognosis is poor due to being HR. We all need to be really responsible and thoughtful with these sorts of retrospective studies and stories about them.
So by this, they could all take Thalidomide for a month and if doesn't work, put their house in order and say goodbye? It is being viewed more and more that it is indeed the HR group that will lead us out to a cure, with recent uncovering that the LR and HR groups have the same molecular structure. I feel like these sorts of stories and the one just shared with me personally may be turning our attention AWAY from the HR group instead of toward them. It is currently true that well known facilities and docs can get the HR group into CR now, where before they could not. They just can't keep it sustained - yet!
And the incurable comment is not the prevailing view even by some big names outside of Arkansas and Huntsman. One leading researcher you quote a lot here recently said in a IMF panel forum, "Cure is creeping into the Myeloma vocabulary..."
And... finally.... what is not in the abstract or this story is what are they using to determine HR. The old tests, FISH and the like are not determining factors anymore in some of the big research facilities, but is still often viewed universally as HR. I don't have access to the whole paper so it's hard for me to know all the details and easy for me to make assumptions about what is missing.
There's a mirror side to all of this. It should be pointed out that just as poor response increases the likelihood of a poor outcome, the reverse is (therefore) also true.
A good response to novel agents increases the likelihood of a positive outcome.
Frank Heasley, Ph.D.
Bacteriology, UC Berkeley, 1978 (retired)
Julie and Staff: I find this article quite interesting although I question the ability to get meaningful statistics from such a diversely exposed group of patients.
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