Extended Use Of Revlimid Plus Dexamethasone Delays Progression Of Relapsed / Refractory Myeloma
Results from a recent retrospective study conducted in France indicate that long-term treatment with Revlimid plus dexamethasone is effective in delaying disease progression in relapsed multiple myeloma patients.
Among patients treated with Revlimid (lenalidomide) plus dexamethasone (Decadron) for at least two years, almost all (96 percent) responded to treatment, with 74 percent achieving at least a very good partial response.
Patients who received treatment for at least three years were significantly more likely to have not yet progressed 37 months after beginning treatment (91 percent), compared to patients who were treated for two to three years (78 percent).
Based on this finding, the researchers state that it is important for patients to continue Revlimid-dexamethasone therapy as long as they are able to tolerate the regimen.
However, nearly half of the patients experienced serious side effects that caused them to lower their dose of Revlimid or to completely stop the regimen.
According to the French researchers, the findings from this study are comparable to those from previous studies of Revlimid-plus-dexamethasone therapy in relapsed myeloma, which frequently have found that treatment for at least one year results in better outcomes that treatment for shorter periods of time (see, for example, this recent Beacon article).
Background
Novel drugs such as Revlimid, Velcade (bortezomib), and thalidomide (Thalomid) have become common treatment options for relapsed and refractory myeloma patients.
These drugs have been shown to be able to provide long-term control of myeloma.
The investigators of this study state that the short-term efficacy and safety of Revlimid are well known, but the efficacy and tolerability of long-term exposure to Revlimid-dexamethasone therapy are less well known.
They were therefore interested in assessing the long-term safety and efficacy Revlimid plus dexamethasone therapy, which is approved for the treatment of relapsed/refractory myeloma patients who have received at least one prior treatment.
Study Design
Researchers from France retrospectively analyzed the records of 50 relapsed myeloma patients who had received combination therapy with Revlimid and dexamethasone. The median age of the patients was 58 years.
Eight percent of the patients had one or both of the chromosomal abnormalities del(17p) and t(4;14), as determined by fluorescence in situ hybridization (FISH). The presence of these abnormalities is generally considered a sign that a patient's myeloma will be more difficult to treat (see related Beacon news article).
Revlimid starting doses ranged from 10 mg to 25 mg daily, and the majority of patients received 40 mg of dexamethasone once a week.
All patients received Revlimid plus dexamethasone for at least two consecutive years, and 56 percent received Revlimid plus dexamethasone for at least three years.
Half of the patients received the two-drug combination at their first relapse, 38 percent received it at their second relapse, and 12 percent received it later in the course of their disease. The median time from diagnosis to start of Revlimid-dexamethasone therapy was 4.5 years.
The median follow-up time was four years.
Results
Overall, 96 percent of the patients responded to Revlimid-dexamethasone therapy, with 74 percent achieving at least a very good partial response.
The median time to first response was two months, and the median time to best response was 4.5 months.
Age, number of previous lines of therapy, starting Revlimid dose, and dose reductions did not appear to significantly impact response rates.
The investigators note that the 96 percent overall response rate they observed in their study is higher than what has been seen in other studies of Revlimid+dexamethasone in relapsed myeloma patients.
They believe this may be due, in part, to fewer patients in their study having high-risk chromosomal abnormalities than is usually the case.
Patients who received Revlimid for two to three years achieved deeper responses than those who received it for at least three years (82 percent achieved at least a very good partial response versus 67 percent, respectively).
However, the percent of patients who had not yet progressed at 37 months was significantly greater in patients who received the combination for at least three years compared to those who received it for two to three years (91 percent versus 78 percent, respectively).
The median time to progression for all patients was not reached, but the researchers estimated that 52 percent of patients would not yet have progressed four years after starting Revlimid-dexamethasone therapy.
The researchers state that long-term exposure to Revlimid-dexamethasone has an acceptable safety profile.
Overall, 46 percent of the patients developed severe side effects. The most common severe side effects were low white blood cell counts (16 percent), low platelet counts (6 percent), and low red blood cell counts (6 percent).
In addition, 20 percent of patients developed a blood clot in a vein. This is a higher rate than observed in other studies (see related Beacon news article). The median time till the development of a blood clot was five months. In all but one case, the patients were receiving treatment to prevent blood clots at the time of the clot occurred.
The rate of side effects was similar among those treated with Revlimid for two to three years and those treated for at least three years.
In total, 38 percent of the patients stopped treatment, with 18 percent stopping treatment due to serious side effects.
In addition, 6 percent of the patients developed a secondary cancer at a median time of four years after starting Revlimid therapy. No patients who were treated with Revlimid for more than three years, however, developed a second cancer.
The researchers note that the safety profile of Revlimid+dexamethasone was similar in all patients, regardless of age or number of prior therapies. They also add that outcomes – including response rates, duration of treatment, and time to progression – were similar for patients who did and those who did not experience serious side effects.
For more information, please refer to the study in the journal Cancer (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
- Adding Clarithromycin To Velcade-Based Myeloma Treatment Regimen Fails To Increase Efficacy While Markedly Increasing Side Effects
- Sustained Complete Response To Initial Treatment Associated With Substantial Survival Benefit In Multiple Myeloma
Good French retrospective study, but too bad they included few high risk MM patients (8 versus expected 20% of patients). They did not break down the results based on that variable, I'm sure because the high risk group comprised only four patients! I am one of those that recurred just six months after starting Revlimid and dex prophylactic therapy, after recovering from my auto stem transplant. In retrospect, prophylaxis with low dose Revlimid (10 mg) is probably not a good idea in high risk patients, because the Imibs (including Pomalidomide) are less likely to work afterward when the inevitable relapse occurs. Again, a genomic analysis of the original tumor can guide targeted therapy, especially in high risk disease.
I don't understand their statistics re secondary cancers: how can there be a 6% risk of that with a median 4 year Revlimid prophylaxis, when no patients got secondary cancers after more than three years of Revlimid use? Am I missing something?
Hi Beacon Staff, would there be any similar retrospective studies showing that Revlimid alone delayed progression of RR myeloma? They did not give the dose of 'dex' in the abstract, but you did mention that 20% of the patients experienced venous clots. With 'dex' there is a higher risk of venous clots than with revlimid alone, according to the abstract. So if there was a similar study just with revlimid, it could be a safer alternative to using 'dex'. Thanks for any insight on this!
Hey there....I really don't understand the statement above that said:
"Patients who received Revlimid for two to three years achieved deeper responses than those who received it for at least three years (82 percent achieved at least a very good partial response versus 67 percent, respectively)."
So the point would be to take less, rather than more, Revlimid? What am I missing?
Thanks,
S.
Thanks for your comments and questions, Jan, Nancy, and Steve.
Jan - Regarding the secondary cancer data in the study, although it may seem a bit confusing, there is no contradiction in what the authors found.
Three patients (6 percent) in the study developed secondary cancers. All of these patients were on Rev-dex treatment for 2-3 years. None of the patients who received Rev-dex for 3 years or more developed secondary cancers. In the patients who developed secondary cancers, those cancers developed a median of 4 years after the Rev-dex treatment was initiated.
Nancy - As you may recall from the discussion in the comments to a previous Beacon article about long-term treatment with Rev-dex, there has been only one notable study looking at long-term treatment with just Revlimid alone.
As for the dose of dex received by patients in the study, the authors provide this information: "The majority of patients received Dex at a dose of 40 mg weekly; the remaining patients received Dex at a dose of 10 mg or 20 mg weekly; 40 mg daily from day 1 to day 4 every 28 days; or 40 mg at days 1, 4, 8, and 11 every 28 days."
Steve - The statistics that you quote, which are in our article, are correct. Patients in the study who were treated with Rev-dex for just 2-3 years were more likely to achieve at least a VGPR than patients in the study who were treated for 3 years or more.
However, as we also note in the study, patients who stayed on treatment for at least 3 years had the longest progression-free survival.
What most likely happened in the study -- and remember, it is a retrospective study -- is that patients did not stay on treatment for 3 years or longer either because of (a) side effects, or (b) because they achieved a VGPR or CR, and they and their doctors decided to take them off treatment.
So, yes, part of what you're suggesting that one could conclude from the study is correct. If side effects of the treatment are a problem, the authors would say it is better to reduce the dose rather than go off the treatment completely.
But the authors are also suggesting that, if you achieve a VGPR or CR after longer-term treatment with Rev-dex, you still should continue treatment.
Remember, though, that this study looks only at progression-free survival. This is important because. Recall, for example, that almost all studies of Revlimid maintenance therapy have shown a benefit in terms of progression-free survival, but only one of those studies has shown a benefit in terms of overall survival.
Thanks, Beacon Staff..I now realize that the French study and the Greek study both used 'dex' with the revlimid. Thanks for elaborating on the study though. I will be curious to know if the conundrum of 'progression free survival' not extending 'over all survival' will be better defined in future studies.
Maybe I missed it, but were these patients Rev naive or previously treated with Rev? I would be interested in what the percentages were on that.
Good question, Perseverance.
The authors do not explicitly say whether the patients in the study were Revlimid-naive before they were treated with Rev-dex in this study. However, it's very likely that they were -- that is, it's likely that all the patients in the study had never been treated with Revlimid before they started the Rev-dex regimen examined in this study.
That said, at least 9 of the patients (18 percent) in the study were treated with thalidomide before starting treatment with Rev-dex. Thalidomide is the same class of drugs as Revlimid.
I have just completed my fifth cycle of rev-dex. The last three blood test m protein results have been 4,5,5 this is coming from 13 protien at time of starting treatment. My question is - does rev-dex generally bring the m protien down to zero or is it normal to carry an m protien of 5. and if so what type of damage could be ongoing at 5.
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