Hello! I have been posting a lot lately, but I have lots of questions. Hoping for some guidance here.
My mother's myeloma specialist has recommended that, after failing her second autologous stem cell transplant and Pomalyst maintenance after 5 months (most likely an extramedullary relapse), she go on a clinical trial. The trial consists of ABT-199 (venetoclax), Velcade and dexamethasone. She has had Velcade and dex before, but ABT-199 is new.
Here's the issue: I have read a lot about how wonderful ABT-199 is for the 11;14 translocation. My mother is not 11;14, she has the 4:14 translocation (also del 13 and gain 1q).
I'm not understanding why this would be recommended for someone who is not 11;14. Can anyone shed some light? Many thanks!
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BeatMyeloma - Name: BeatMyeloma
- Who do you know with myeloma?: My mother
- When were you/they diagnosed?: Jan. 2008
- Age at diagnosis: 54
Re: ABT-199 (venetoclax) & multiple myeloma without t(11;14)
The trial consists of ABT-199, Velcade and dexamethasone. She has had Velcade and dex before but ABT-199 is new.
First of all, it is a TRIAL. Trials imply that they (MD's) don't necessarily know with certainty, which drugs are effective with which FISH carotype of myeloma. In this era of Novel drugs, combination Therapy is the emerging Standard of care.
Many Trials are opening up, due to the need to understand "Combination Therapy" better.
Second, cost and availability. Maybe a Trial is the only way to get the drugs to your Mom. ? Especially the combinations involved.
Third, perhaps your Mom has a medical condition(s) which contraindicates usage of other certain drugs--ie. Pomalyst, Krypolis, Elotzumab, etc. ( ie. Kidney disease, Cardiac, Coagulation issues, low platelets, etc )
Fourth, binding sites. Is she CD20+ ?; CD79 + ? etc.
One of the things investigators are looking at is the propensity for Myeloma cells to "cloak" themselves, and the use of specific drugs "attaching to specific proteins" which opens the door to allow the use / effectiveness of other drugs, like Velcade , Revlimid, and Dex...and their progeny.
Kind of like the attack at Normandy in WWII--have to open a beachhead first, before the heavy stuff can get off the beach, and move inland, where it can effectively fight multiple myeloma.
That may not be the best analogy, but it serves as a model to support the possibilities of combined therapies.
ABT-199 might just be a drug that attaches to her form of cell Proteins, opens the access, and allows Velcade and Revlimid to go in and "do their thing". On it's own ABT-199 may not be "effective against 4,14", but maybe it opens the door.
Maybe that's all you / Mom needs it to do ?
I'd just ask her Oncologist ..."what's the game plan, Doc " ?
Good luck.
First of all, it is a TRIAL. Trials imply that they (MD's) don't necessarily know with certainty, which drugs are effective with which FISH carotype of myeloma. In this era of Novel drugs, combination Therapy is the emerging Standard of care.
Many Trials are opening up, due to the need to understand "Combination Therapy" better.
Second, cost and availability. Maybe a Trial is the only way to get the drugs to your Mom. ? Especially the combinations involved.
Third, perhaps your Mom has a medical condition(s) which contraindicates usage of other certain drugs--ie. Pomalyst, Krypolis, Elotzumab, etc. ( ie. Kidney disease, Cardiac, Coagulation issues, low platelets, etc )
Fourth, binding sites. Is she CD20+ ?; CD79 + ? etc.
One of the things investigators are looking at is the propensity for Myeloma cells to "cloak" themselves, and the use of specific drugs "attaching to specific proteins" which opens the door to allow the use / effectiveness of other drugs, like Velcade , Revlimid, and Dex...and their progeny.
Kind of like the attack at Normandy in WWII--have to open a beachhead first, before the heavy stuff can get off the beach, and move inland, where it can effectively fight multiple myeloma.
That may not be the best analogy, but it serves as a model to support the possibilities of combined therapies.
ABT-199 might just be a drug that attaches to her form of cell Proteins, opens the access, and allows Velcade and Revlimid to go in and "do their thing". On it's own ABT-199 may not be "effective against 4,14", but maybe it opens the door.
Maybe that's all you / Mom needs it to do ?
I'd just ask her Oncologist ..."what's the game plan, Doc " ?
Good luck.
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Rneb
Re: ABT-199 (venetoclax) & multiple myeloma without t(11;14)
BeatMyeloma
Good morning. Here are two links related to a venetoclax study; perhaps you have seen them before, but here they are:
https://myelomabeacon.org/docs/asco2015/8576.pdf
http://meetinglibrary.asco.org/content/151052-156
Since its added to Velcade and dex, it would likely be additive (hopefully synergistic) with the doublet. So its worth a trial, but it's new. The study stated it works if the multiple myeloma expresses a high BLC2 to MCL1 ratio. I do not know what that is, however, you could ask your doctor is it something you could test for. If your mom's condition is positive for that condition, very good chance you would get a least some response (as it has been tested in that trial in about 30 patients). The study indicated that it was not initially only for t(11,14) +, but they did notice good results for that subgroup.
Another option to consider are the monoclonal antibodies. I have heard (I believe Dr. Richardson from Dana-Farber) stating that the MAB's seem to have effectiveness regardless of cytogenetics. If I understand the explanation properly, it is because the MAB's work based on interacting with multiple myeloma cell surfaces, and does not care what is inside. The bad FISH characteristics are internal to the multiple myeloma, but the MAB's don't care and have nothing to do with the internals, their mode of action is based on the surface of the cells.
Good morning. Here are two links related to a venetoclax study; perhaps you have seen them before, but here they are:
https://myelomabeacon.org/docs/asco2015/8576.pdf
http://meetinglibrary.asco.org/content/151052-156
Since its added to Velcade and dex, it would likely be additive (hopefully synergistic) with the doublet. So its worth a trial, but it's new. The study stated it works if the multiple myeloma expresses a high BLC2 to MCL1 ratio. I do not know what that is, however, you could ask your doctor is it something you could test for. If your mom's condition is positive for that condition, very good chance you would get a least some response (as it has been tested in that trial in about 30 patients). The study indicated that it was not initially only for t(11,14) +, but they did notice good results for that subgroup.
Another option to consider are the monoclonal antibodies. I have heard (I believe Dr. Richardson from Dana-Farber) stating that the MAB's seem to have effectiveness regardless of cytogenetics. If I understand the explanation properly, it is because the MAB's work based on interacting with multiple myeloma cell surfaces, and does not care what is inside. The bad FISH characteristics are internal to the multiple myeloma, but the MAB's don't care and have nothing to do with the internals, their mode of action is based on the surface of the cells.
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JPC - Name: JPC
Re: ABT-199 (venetoclax) & multiple myeloma without t(11;14)
Initial results also were made available at ASCO for ABT-199 combined with Velcade and dexamethasone. Here's is the poster, https://myelomabeacon.org/docs/asco2015/8580.pdf, and here's the abstract: http://meetinglibrary.asco.org/content/147784-156 .
Unlike the abstract JPC mentioned, this study does not focus on results for t(11;14).
I think it makes sense to try this trial at this point. ABT-199 is still in the early stages of development, so, if your mother doesn't do the trial now, it's not clear she would have easy access to another trial for the drug at some other point. The drug won't be FDA approved -- if it gets that far -- for several years, and trials for new therapies come and go. You can't always predict when and where they'll be available.
In contrast, your mother should have easy access to monoclonal antibodies, such as daratumumab and elotuzumab, in the future. There are early access programs, and the two drugs I mentioned are already under FDA review, which means they could be approved for use outside of clinical trials within the next 6-9 months.
I hope your mother responds well to the combination therapy. Good luck!
Unlike the abstract JPC mentioned, this study does not focus on results for t(11;14).
I think it makes sense to try this trial at this point. ABT-199 is still in the early stages of development, so, if your mother doesn't do the trial now, it's not clear she would have easy access to another trial for the drug at some other point. The drug won't be FDA approved -- if it gets that far -- for several years, and trials for new therapies come and go. You can't always predict when and where they'll be available.
In contrast, your mother should have easy access to monoclonal antibodies, such as daratumumab and elotuzumab, in the future. There are early access programs, and the two drugs I mentioned are already under FDA review, which means they could be approved for use outside of clinical trials within the next 6-9 months.
I hope your mother responds well to the combination therapy. Good luck!
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JimNY
Re: ABT-199 (venetoclax) & multiple myeloma without t(11;14)
Thank you all so much. It is humbling to have patients and caregivers take time out of their busy days to respond to my problem.
Rneb, I don't think it's a health issue so much. But she doesn't seem to respond to IMIDs too much. And you're right, there could be some sort of binding issue. Her hematologist seemed awfully excited about it, and said they had seen excellent responses in her genetic subtype.
JPC and JimNY, I'm excited about the MOABs too. I think that since this is an earlier trial, better to do first since the others will hopefully be improved soon.
I'm trying to remember that even though this is just a phase 1 trial designed to answer questions about dosing, researchers still care about results. And I do believe my mother's hematologist wants the best for her (and wants this trial to succeed), and would not have recommended it if she didn't think it would have a chance of working. The other option she offered was CYCLONE (Cytoxan, Kyprolis, Thaidomid and dex) but highly recommended the trial.
Rneb, I don't think it's a health issue so much. But she doesn't seem to respond to IMIDs too much. And you're right, there could be some sort of binding issue. Her hematologist seemed awfully excited about it, and said they had seen excellent responses in her genetic subtype.
JPC and JimNY, I'm excited about the MOABs too. I think that since this is an earlier trial, better to do first since the others will hopefully be improved soon.
I'm trying to remember that even though this is just a phase 1 trial designed to answer questions about dosing, researchers still care about results. And I do believe my mother's hematologist wants the best for her (and wants this trial to succeed), and would not have recommended it if she didn't think it would have a chance of working. The other option she offered was CYCLONE (Cytoxan, Kyprolis, Thaidomid and dex) but highly recommended the trial.
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BeatMyeloma - Name: BeatMyeloma
- Who do you know with myeloma?: My mother
- When were you/they diagnosed?: Jan. 2008
- Age at diagnosis: 54
Re: ABT-199 (venetoclax) & multiple myeloma without t(11;14)
Well, there won't be any ABT-199. She is in acute renal failure. This happened to her at diagnosis in January 2008, with a creatinine of 2.7. It is now at 3.5. We're hoping she can turn it around so she can begin receiving VTD-PACE. Seems like that is very harsh but might be effective.
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BeatMyeloma - Name: BeatMyeloma
- Who do you know with myeloma?: My mother
- When were you/they diagnosed?: Jan. 2008
- Age at diagnosis: 54
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