Study Confirms Survival Benefit Of Revlimid-Dexamethasone Combo In Elderly Relapsed / Refractory Myeloma Patients

Results from a recent retrospective study confirm that treatment with a combination of Revlimid and dexamethasone slows disease progression and improves survival in elderly patients with relapsed or refractory myeloma.
However, findings from the study also indicate that certain side effects, such as anemia and blood clots, occurred more frequently in elderly patients.
Novel agents such as Revlimid (lenalidomide), thalidomide (Thalomid), and Velcade (bortezomib) are commonly used to treat relapsed and refractory myeloma.
A previous study found that Revlimid in combination with dexamethasone (Decadron) is effective in patients over 75 years of age with relapsed myeloma (see related Beacon news).
FDA approval of the Revlimid-dexamethasone combination was based on two randomized Phase 3 studies that demonstrated its efficacy in people with relapsed or refractory myeloma. Patients were enrolled in those studies from 2003 to 2005.
In the current study, researchers retrospectively analyzed pooled data from these two trials to assess if treatment outcome was associated with age.
Among the 704 patients included in the studies, 55 percent were below 65 years of age, 33 percent were between 65 and 74 years, and 12 percent were 75 years or older.
Results from the analysis showed that treatment with Revlimid and dexamethasone was effective in all age groups, including patients over 65 years of age.
In all age groups, a greater percent of patients responded to Revlimid-dexamethasone treatment as compared to treatment with dexamethasone alone.
Specifically, among patients below 65 years of age, 61 percent responded to Revlimid-dexamethasone as compared to 22 percent who responded to dexamethasone alone. Among patients 65 to 74 years of age, 54 percent responded to Revlimid-dexamethasone versus 21 percent who responded to dexamethasone. Finally, among patients 75 years or older, 70 percent responded to Revlimid-dexamethasone versus 21 percent who responded to dexamethasone.
Revlimid-dexamethasone also provided a progression-free survival advantage for each of the age groups, as compared to dexamethasone alone.
For the youngest group, median progression-free survival was 11.1 months for Revlimid-dexamethasone versus 4.6 months for dexamethasone alone. For patients between 65 and 74 years, progression-free survival was 9.4 months versus 4.6 months, respectively. For the oldest group of patients, progression-free survival was 14.1 months versus 3.8 months, respectively.
Median overall survival was also higher for each of the age groups treated with Revlimid-dexamethasone as compared to dexamethasone alone, but the survival differences between the two treatment regimens were not statistically significant.
Specifically, among patients below 65 years of age, the median overall survival time was 43.9 months for those treated with Revlimid-dexamethasone as compared to 36.2 months for those treated with dexamethasone alone. Among patients 65 to 74 years of age, overall survival was 33.3 months for the Revlimid-dexamethasone group versus 23.3 months for the dexamethasone-only group. Finally, among patients 75 years or older, overall survival was 34.3 months for Revlimid-dexamethasone-treated patients versus 19.5 months for those treated only with dexamethasone.
The results also showed that the occurrence of some, but not all, side effects of Revlimid-dexamethasone treatment increased with age.
Anemia (low red blood cell counts), deep-vein thrombosis (blood clots in deep veins), peripheral neuropathy (pain, tingling, or loss of sensation in the extremities), and gastro-intestinal disorders occurred more frequently in older patients.
Older patients were also more likely to require dose reductions and to need them earlier in their course of treatment than younger patients. The first reduction was required after a median of 4.3 months of treatment in patients below 65 years of age, but 2.6 months in patients who were 65 or older.
For more information, please see the study in the International Journal of Hematology (abstract).
Related Articles:
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma
- Sustained Complete Response To Initial Treatment Associated With Substantial Survival Benefit In Multiple Myeloma
- Adding Clarithromycin To Velcade-Based Myeloma Treatment Regimen Fails To Increase Efficacy While Markedly Increasing Side Effects
Is it correct that the patients were on this 'maintenance' therapy for 2 yrs i.e. 2003-2005 (period of retrospective analysis.
What was the incidence of SPM over that period in this population?
Or was the only parameter analyzed from the pooled data, age related outcome?
Suzierose, patients were treated until their disease progressed or they were unable to tolerate treatment.
This particular analysis only looked at age-related outcomes.
The rate of second cancers in these two studies were reported previously, though:
http://www.myelomabeacon.com/news/2012/05/07/fda-issues-extensive-update-about-revlimid-lenalidomide-and-second-cancers/
"The analyses also show that relapsed and refractory myeloma patients treated with Revlimid and dexamethasone (Decadron) are more likely to develop a second cancer than patients treated with dexamethasone alone.
"Specifically, data from the two clinical trials that supported the FDA’s approval of Revlimid show that 3.98 percent of relapsed and refractory myeloma patients developed a second cancer during each year of treatment with Revlimid and dexamethasone, compared to 1.38 percent of patients treated with dexamethasone and placebo. A key contributor to the different rates of second cancer was a noticeably higher rate of non-melanoma skin cancer among the patients treated with Revlimid."
So,let me see if I understand this.... Patients treated with rev/ dex maintenance remained progression free for 43.9 months. This would be the group I'm in under 65.
So my question is, you stay on the rev/ dex till it stops working? And Is the dose 25 mg rev? And what dose of dex.
I'm asking because I just reached CR on rev/ dex after 4 months, and the question is do I keep on it or go off? My hem/onc says I can really go either way?......
So I'm trying to get as much info as I can.....
Thanks so much, Christina
Christina
The 43.9 month number for the under 65 group(treated with Rev and dex) pertains to median overall SURVIVAL. Progression-free survival for this group of Rev-dex patients is shorter, lasting for a median of 11.1 months. Of course, I would like to know what the progession-free survival time is for subgroups of patients, such as those with low-risk disease.
Also: keep in mind that these studies apply ONLY to patients who have relapsed after previous treatment or have become refactory to treatment. If you have not been treated before, these numbers do not apply. Your message is not clear on your treatment status.
Indeed,if you are a NEWLY diagnosed patient being treated with Rev plus dex, the median progression-free survival after treatment is about 28 months and with the addition of Biaxin - apparently 4 years. See, for example, the following abstract, which includes a free link to the entire article. http://onlinelibrary.wiley.com/doi/10.1002/ajh.21777/abstract
P.S. I am three months into the Rev plus dex (plus clarithromycin) treatment and, assuming I achieve a CR, do not plan on using any drugs during maintenance. But this decision will likely depend on your initial presentation, overall health, risk-factors etc.
No, I am not newly diagnosed. Was diagnosed in 2005, sct in 2006, lasted in CR till 2010.
Did rev / dec for 8 months, CR for 4 of those. Then, no drugs for 11 months, and then relapsed eith very small m protein, .3
I decided to stare rev/ dex again, and again CR in four months. I assume
I'm low risk, although no one has ever said that to me.
So , now I face, go off like I did last time or stay on maintenance. That's why when I saw this study I was in interested in the 43 months progression free statistic.
Thanks for your interpretation. I'm not sure which way to go, my hem/ onc leans toward going off, so as to not build resistance to the 4
Rev/dex, but since this is my second time round , not sure?
Hope you get CR soon, I think that 4 month things start to turn around.
Best wishes,
Christina
Thanks for the clarification. I think you are taking the right approach -- going for maintenance - given the absence of statistically significant evidence in this study that maintenance with these drugs improves overall survival - indeed it could be reducing it for all we know -- why build up resistance?
Dex exacts a huge toll on the body in the long-run and despites it profound and excellent action, revlimid also, in some sense, resets the immune system, appears to increase the risk of secondary malignancies, and confers resisance while potentially selected for new, more aggressive clones.
Like you, I would like to keep my options open down the road, not just with revlimid, but also with pomalidomide, velcade, carfilzomib, etc.
Best wishes
Whoops -- I meant going for DRUG-FREE maintenance as the right approach...
Thanks so much for those thoughts. I am really on the fence about this , so your input really helps .
Best wishes for. CR soon.
Christina
I am taking revlimid and dex. The skin on my arms is very susceptable to brusing under the skin. I don't bleed but get a large blood bruise that sometimes looks black. After a week or two it usually slowly disappears. In mean time I look like I was mugged. Also day I take Dex my hands cramp. Not bad sometimes and very painful other times. Any suggestions or similarities to this.
my husband has been taken off revlimid-concerns about it causing other cancers-he also has melanoma-should i/we be frightened. he has been in remission with myeloma since taking revlimid &dexamethasone.