Has somebody thought about using daratumumab as a consolidation therapy to get deeper response?
Would it make sense for a newly diagnosed patient to use daratumumab to try to get rid of difficult subclones after initial therapy?
I am into treatment as a newly diagnosed multiple myeloma patient with Velcade, thalidomide, and dexamethasone (VTD), an autologous stem cell transplant, and VTD consolidation.
Any thoughts on this issue?
Kind regards,
John C
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JohnC - Name: JohnC
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: April 2014
- Age at diagnosis: 47
Re: Daratumumab as a consolidation therapy
Hi JohnC,
If potential long-term drug free remission is your goal of therapy, adding daratumumab in as a consolidation after the therapy you outlined could be helpful. Daratumumab shows single-agent activity in relapsed patients, which is rare in myeloma. It should do great when used early in disease course. Daratumumab as consolidation would likely only be available in a clinical trial. Even though drugs can be prescribed off label here in the U.S., I doubt many insurance companies would approve it for that use since it is expensive and there is little or no data to support its use in that role.
I like that you are looking at strong consolidation therapy after your auto. Hopefully you will reach an MRD negative state after your consolidation with VTD. There was a study that showed great results for patients that went MRD negative (molecular testing) with that strategy. Note these patients did not need maintenance.
Abstract:
Polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis is a useful prognostic tool in multiple myeloma, although its long-term impact still needs to be addressed. This report presents the updated results of the GIMEMA-VEL-03-096 trial.
Thirty-nine multiple myeloma patients receiving bortezomib-thalidomide-dexamethasone after autologous transplantation were monitored for MRD [minimal residual disease] by both nested and real-time quantitative-PCR until relapse. Our data confirm the strong impact of MRD on survival: overall survival was 72% at 8 years median follow-up for patients in major MRD response versus 48% for those experiencing MRD persistence (P=0.041).
In addition, MRD kinetics resulted predictive for relapse: indeed median remission duration was not reached for patients in major MRD response, 38 months for those experiencing MRD reappearance and 9 months for patients with MRD persistence (P<0.001).
Moreover:
(1) 26 patients achieving major MRD response (67%) benefit of excellent disease control (median TNT [time to next therapy]: 42 months);
(2) MRD reappearance heralds relapse, with a TNT comparable to that of MRD persistence (9 versus 10 months, P=0.706);
(3) the median lag between MRD reappearance and need for salvage treatment is 9 months.
These results suggest the usefulness of a long-term MRD monitoring in multiple myeloma patients and the need for maintenance or pre-emptive treatments ensuring durable responses.
Reference:
S Ferrero et al, "Long-term results of the GIMEMA VEL-03-096 trial in multiple myeloma patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival", Leukemia, July 16, 2014 (abstract)
Mark
If potential long-term drug free remission is your goal of therapy, adding daratumumab in as a consolidation after the therapy you outlined could be helpful. Daratumumab shows single-agent activity in relapsed patients, which is rare in myeloma. It should do great when used early in disease course. Daratumumab as consolidation would likely only be available in a clinical trial. Even though drugs can be prescribed off label here in the U.S., I doubt many insurance companies would approve it for that use since it is expensive and there is little or no data to support its use in that role.
I like that you are looking at strong consolidation therapy after your auto. Hopefully you will reach an MRD negative state after your consolidation with VTD. There was a study that showed great results for patients that went MRD negative (molecular testing) with that strategy. Note these patients did not need maintenance.
Abstract:
Polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis is a useful prognostic tool in multiple myeloma, although its long-term impact still needs to be addressed. This report presents the updated results of the GIMEMA-VEL-03-096 trial.
Thirty-nine multiple myeloma patients receiving bortezomib-thalidomide-dexamethasone after autologous transplantation were monitored for MRD [minimal residual disease] by both nested and real-time quantitative-PCR until relapse. Our data confirm the strong impact of MRD on survival: overall survival was 72% at 8 years median follow-up for patients in major MRD response versus 48% for those experiencing MRD persistence (P=0.041).
In addition, MRD kinetics resulted predictive for relapse: indeed median remission duration was not reached for patients in major MRD response, 38 months for those experiencing MRD reappearance and 9 months for patients with MRD persistence (P<0.001).
Moreover:
(1) 26 patients achieving major MRD response (67%) benefit of excellent disease control (median TNT [time to next therapy]: 42 months);
(2) MRD reappearance heralds relapse, with a TNT comparable to that of MRD persistence (9 versus 10 months, P=0.706);
(3) the median lag between MRD reappearance and need for salvage treatment is 9 months.
These results suggest the usefulness of a long-term MRD monitoring in multiple myeloma patients and the need for maintenance or pre-emptive treatments ensuring durable responses.
Reference:
S Ferrero et al, "Long-term results of the GIMEMA VEL-03-096 trial in multiple myeloma patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival", Leukemia, July 16, 2014 (abstract)
Mark
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Mark11
Re: Daratumumab as a consolidation therapy
Mark.
Thanks for thoughtful comments and interesting references.
Having started treatment as an early diagnosed patient without any CRAB criteria, I hope an aggressive treatment will give possibilities to reach MRD negativity. I was thinking that an immunotherapy like daratumumab might help the best this way after I already had reduced a lot of my myeloma tumor burden through VTD induction, a stem cell transplant, and then more VTD.
If it is possible to get daratumumab off label for this kind of use, and if there is some real chance it will increase chances of not getting relapse in 10-15 years, or more, I would happily pay for such a treatment myself.
Thanks for thoughtful comments and interesting references.
Having started treatment as an early diagnosed patient without any CRAB criteria, I hope an aggressive treatment will give possibilities to reach MRD negativity. I was thinking that an immunotherapy like daratumumab might help the best this way after I already had reduced a lot of my myeloma tumor burden through VTD induction, a stem cell transplant, and then more VTD.
If it is possible to get daratumumab off label for this kind of use, and if there is some real chance it will increase chances of not getting relapse in 10-15 years, or more, I would happily pay for such a treatment myself.
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JohnC - Name: JohnC
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: April 2014
- Age at diagnosis: 47
Re: Daratumumab as a consolidation therapy
Hi JohnC,
Apparently you have a doctor's mind. Just so you know there is a study starting soon - IFM2015-01 / HOVON131 - that basically is following your strategy. Randomized trial - one group gets VTD to auto to 2 cycles of VTD consolidation. The other group gets VTD plus daratumumab to auto to 2 cycles of VTD plus DARA consolidation. There is than 2 years of daratumumab maintenance. You design strategies like a myeloma doc!
"A Study to Evaluate Daratumumab in Transplant Eligible Participants With Previously Untreated Multiple Myeloma (Cassiopeia)" (trial information at clinicaltrials.gov)
Mark
Apparently you have a doctor's mind. Just so you know there is a study starting soon - IFM2015-01 / HOVON131 - that basically is following your strategy. Randomized trial - one group gets VTD to auto to 2 cycles of VTD consolidation. The other group gets VTD plus daratumumab to auto to 2 cycles of VTD plus DARA consolidation. There is than 2 years of daratumumab maintenance. You design strategies like a myeloma doc!
"A Study to Evaluate Daratumumab in Transplant Eligible Participants With Previously Untreated Multiple Myeloma (Cassiopeia)" (trial information at clinicaltrials.gov)
Mark
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Mark11
Re: Daratumumab as a consolidation therapy
My mom's doctor is going to have her do an auto transplant this summer with Darzalex maintenance.
Re: Daratumumab as a consolidation therapy
Hello John:
My understanding in the states is that getting a drug off-label is primarily an issue as to whether or not the insurance company will cover it. If you go over the news in the US, going back to the beginning of last year, you will find that Revlimid was approved by the FDA for front line treatment only at the beginning of last year, but was the standard of care in many centers going back to the period 2010 to 2012. So hopeful's observation, if insurance covers it, is a good sign. Once a couple of insurance companies roll over, the rest seem to fall in line, but it is not a hard and fast rule, and some could also hold out. Since elotuzumab was approved after one line of treatment, but daratumumab was approved after 3 lines of treatment, it will be interesting to see which one moves into the front line faster.
My understanding in the states is that getting a drug off-label is primarily an issue as to whether or not the insurance company will cover it. If you go over the news in the US, going back to the beginning of last year, you will find that Revlimid was approved by the FDA for front line treatment only at the beginning of last year, but was the standard of care in many centers going back to the period 2010 to 2012. So hopeful's observation, if insurance covers it, is a good sign. Once a couple of insurance companies roll over, the rest seem to fall in line, but it is not a hard and fast rule, and some could also hold out. Since elotuzumab was approved after one line of treatment, but daratumumab was approved after 3 lines of treatment, it will be interesting to see which one moves into the front line faster.
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JPC - Name: JPC
Re: Daratumumab as a consolidation therapy
Thanks, Mark, for the input. The HOVON 131 seems like an interesting trial, although it will take some time to get the results.
The following article about intra clonal heterogenity also suggests benefits to using different treatments/drugs as early as possible:
Gareth J Morgan, "Evolution, Intra-Clonal Heterogeneity, And Multiple Myeloma," The Myeloma Beacon, Nov 3, 2014
Thanks, JPC, for the update on U.S. off-label policies. This was new for me. Living in Europe (Norway), I guess I still need to pay to get daratumumab, and most likely it will be most convenient to go to the U.S. (New York area), if I can get it arranged.
Best regards
John C
The following article about intra clonal heterogenity also suggests benefits to using different treatments/drugs as early as possible:
Gareth J Morgan, "Evolution, Intra-Clonal Heterogeneity, And Multiple Myeloma," The Myeloma Beacon, Nov 3, 2014
Thanks, JPC, for the update on U.S. off-label policies. This was new for me. Living in Europe (Norway), I guess I still need to pay to get daratumumab, and most likely it will be most convenient to go to the U.S. (New York area), if I can get it arranged.
Best regards
John C
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JohnC - Name: JohnC
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: April 2014
- Age at diagnosis: 47
Re: Daratumumab as a consolidation therapy
Hi John,
We have been thinking along the same lines as you regarding daratumumab and consolidation. And we live in Norway as well. Would be interesting to know if you made any progress on this issue.
Best, M
We have been thinking along the same lines as you regarding daratumumab and consolidation. And we live in Norway as well. Would be interesting to know if you made any progress on this issue.
Best, M
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