In this one, the researchers compared groups of patients who'd been on Revlimid maintenance after autologous stem cell transplant (ASCT) for <12 months, between 12 and 24 months, and >24 months. They found significant improvement in both progression free survival and overall survival with increasing time on maintenance. From the article:
"According to the effective duration of maintenance treatment, we identified three subgroups of patients. Of the patients, 31% had at least 24 months of lenalidomide, 36% underwent between 12 and 24 months, and 33% received less than 12 months. The outcome in these three subgroups was different, with superior survival rates in the subgroup with longest lenalidomide maintenance. Thus, a patient seems to be on the safe side as long as he/she is under maintenance treatment. After stopping lenalidomide maintenance, however, we observed an equal interval of roughly ten months until disease progression independent of the duration of maintenance treatment."
Another aspect of the study that I found interesting was that of the initial group of patients included all 216 who'd received an ASCT, as their hospital's recommendation was that all of them receive Revlimid maintenance. Despite that recommendation, only 149 went onto maintenance. There were a number of reasons given for refusing it, including previous intolerance to the drug, frailty after the ASCT procedure, and doctor preference. There's also some interesting info on secondary malignancies. They recognize that this is a single center, non-randomized study, so there are limitations, but it's still pretty interesting.
Reference:
Amsler, IG, "Prolonged survival with increasing duration of lenalidomide maintenance after autologous transplant for multiple myeloma," Leukemia and Lymphoma, Jan 8 2019 (link to article preview).
Forums
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Mike F - Name: Mike F
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: May 18, 2012
- Age at diagnosis: 53
Re: Another Revlimid maintenance study
Mike,
So in essence, those staying on maintenance longer had better overall results. That leads to the conclusion of oncologists recommending continuous-type treatment. If someone is going to have continuous treatment, then it begs the question of why do an autologous stem cell transplant? Why not just avoid the rigors of the transplant and just do induction treatment followed by indefinite maintenance?
One of the big selling points of a transplant is the potential for a long treatment holiday from a quality-of-life standpoint. Thus the rigors of the procedure are rewarded later. However, if indefinite maintenance is recommended with a transplant, then that selling point disappears.
So in essence, those staying on maintenance longer had better overall results. That leads to the conclusion of oncologists recommending continuous-type treatment. If someone is going to have continuous treatment, then it begs the question of why do an autologous stem cell transplant? Why not just avoid the rigors of the transplant and just do induction treatment followed by indefinite maintenance?
One of the big selling points of a transplant is the potential for a long treatment holiday from a quality-of-life standpoint. Thus the rigors of the procedure are rewarded later. However, if indefinite maintenance is recommended with a transplant, then that selling point disappears.
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: Another Revlimid maintenance study
Hi Ron -
This study only involved maintenance after an autologous transplant. I don't think any conclusions can be drawn from it regarding the possible effectiveness of long-term Revlimid maintenance without the transplant. It does seem to point to continuous treatment in the form of long-term maintenance being more effective than not going that route, but the trade-off in quality of life is something that has to be considered.
This study only involved maintenance after an autologous transplant. I don't think any conclusions can be drawn from it regarding the possible effectiveness of long-term Revlimid maintenance without the transplant. It does seem to point to continuous treatment in the form of long-term maintenance being more effective than not going that route, but the trade-off in quality of life is something that has to be considered.
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Mike F - Name: Mike F
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: May 18, 2012
- Age at diagnosis: 53
Re: Another Revlimid maintenance study
Yeah, I was not looking at effectiveness either. Earlier studies indicated that an ASCT followed by maintenance was better than induction followed by maintenance insofar as progression free survival was concerned. Those earlier studies ;however, found no difference in overall survival between the groups. Those studies compared ASCT with older novel agents and did not include the newer drugs approved recently in combination for front line therapy such as the Darzalex combinations DVD, DPD or DRD (Darzalex, Velcade and Dex), (Darzalex, Pomalist and Dex). Darzalex Revlimid and Dex) or Empliciti based combinations (EVD,ERD or EPD) followed by some form of ongoing maintenance.
The concern with the ASCT has always been that it is a blunt instrument that kills off your bone marrow and re-growth takes time and is a very rigorous procedure. In some people is a very rough process and generally takes 6 months or more of recuperation. Supposedly, if successful (no guarantee), it gives the potential of a deeper response than induction with novel agents alone. Again those studies have not looked at the newer novel agents in induction. Induction with the newer novel agents have not yet been compared to ASCT but they likely will produce a deeper response than the older agents.
In any event any deeper response is lost if maintenance is not continued and the patient will relapse more quickly. The big plus for the ASCT has been that since it produced a deep response only short maintenance was required. Therefore, a patient could go without treatment after the short maintenance period for an extended period of time before a relapse occurred. This study suggests that it would be better to continue maintenance indefinitely from an overall survival perspective. Thus the benefit of having an extended holiday from treatment is not as attractive as it was before. My point simply is that if you thought that it was worth the extra rigors of the ASCT to gain an extended treatment free holiday you might want to rethink that.
The concern with the ASCT has always been that it is a blunt instrument that kills off your bone marrow and re-growth takes time and is a very rigorous procedure. In some people is a very rough process and generally takes 6 months or more of recuperation. Supposedly, if successful (no guarantee), it gives the potential of a deeper response than induction with novel agents alone. Again those studies have not looked at the newer novel agents in induction. Induction with the newer novel agents have not yet been compared to ASCT but they likely will produce a deeper response than the older agents.
In any event any deeper response is lost if maintenance is not continued and the patient will relapse more quickly. The big plus for the ASCT has been that since it produced a deep response only short maintenance was required. Therefore, a patient could go without treatment after the short maintenance period for an extended period of time before a relapse occurred. This study suggests that it would be better to continue maintenance indefinitely from an overall survival perspective. Thus the benefit of having an extended holiday from treatment is not as attractive as it was before. My point simply is that if you thought that it was worth the extra rigors of the ASCT to gain an extended treatment free holiday you might want to rethink that.
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: Another Revlimid maintenance study
I think that in some cases there is some middle ground here. If the ASCT was successful and complete remission was maintained through a two-year maintenance period, it may make sense to go off maintenance treatment while carefully monitoring test results. Usually if progression starts after complete remission it comes slowly and treatment can be re-started.
There is research to support the view that periodic drug "holidays" while the disease is at a low level can avoid drug resistance and maintain the efficacy of the drugs that have worked in the past for that patient.
There is research to support the view that periodic drug "holidays" while the disease is at a low level can avoid drug resistance and maintain the efficacy of the drugs that have worked in the past for that patient.
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goldmine848 - Name: Andrew
- When were you/they diagnosed?: June 2013
- Age at diagnosis: 60
Re: Another Revlimid maintenance study
This article on "adaptive therapy" while not myeloma-specific illustrated the point that I made above:
https://www.mdedge.com/hematology-oncology/article/168663/immunotherapy/tumor-heterogeneity-central-foe-war-cancer
https://www.mdedge.com/hematology-oncology/article/168663/immunotherapy/tumor-heterogeneity-central-foe-war-cancer
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goldmine848 - Name: Andrew
- When were you/they diagnosed?: June 2013
- Age at diagnosis: 60
Re: Another Revlimid maintenance study
Ron -
I'd agree that this study does suggest that an extended drug-free holiday might not be as good as just staying with the maintenance. It will be interesting to see whether this is borne out by future studies.
Andrew - It makes sense that there could be some room for shorter holidays from maintenance treatment. This particular study seems to indicate that resistance to Revlimid treatment after an ASCT doesn't happen quickly and the benefits continue for the long term. There's no information on compliance with the maintenance protocol, though, and you have to wonder if some of the people who were in the >24 month maintenance cohort might have taken some short holidays on their own. That's a long time to stick with taking a drug like that, day in and day out.
I'd agree that this study does suggest that an extended drug-free holiday might not be as good as just staying with the maintenance. It will be interesting to see whether this is borne out by future studies.
Andrew - It makes sense that there could be some room for shorter holidays from maintenance treatment. This particular study seems to indicate that resistance to Revlimid treatment after an ASCT doesn't happen quickly and the benefits continue for the long term. There's no information on compliance with the maintenance protocol, though, and you have to wonder if some of the people who were in the >24 month maintenance cohort might have taken some short holidays on their own. That's a long time to stick with taking a drug like that, day in and day out.
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Mike F - Name: Mike F
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: May 18, 2012
- Age at diagnosis: 53
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