› Forums › General Melanoma Community › U.S. approval of Merck cancer immunotherapy expected soon
- This topic has 21 replies, 4 voices, and was last updated 10 years, 8 months ago by
kalisama.
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- August 25, 2014 at 2:26 pm
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- August 25, 2014 at 3:22 pm
thanks for the post, eagerly awaiting approval. does anyone have info on PD-1's ability to cross blood brain barrier? i haven't seen any publications that address this yet.
best of health to all,
kali-
- August 25, 2014 at 6:12 pm
My understanding is that the mechanism of immunotheraputic drugs makes "crossing of the blood brain barrier" realtively unimportant. It is not the ability of the drug to cross the border but that of the immune system to operate on both sides of the border. This is not in doubt. So PD-1 should be as effective in the brain as out because of its influence on the immune system, not because of its presene in the brain.
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- August 27, 2014 at 2:35 pm
Thank you for this perspective, I will certainly bring it to my oncologist. I wonder why he and my radiology oncologist have both told me that one of the reasons I keep developing brain mets is that the Mekinist/Tafinlar does not cross the BBB. If anyone can help me formulate the proper questions to ask them when I see them in a few weeks, I'd greatly appreciate the help. If this is worthy of a separate thread, I'll be happy to start one.
Bless,
kali -
- August 27, 2014 at 2:35 pm
Thank you for this perspective, I will certainly bring it to my oncologist. I wonder why he and my radiology oncologist have both told me that one of the reasons I keep developing brain mets is that the Mekinist/Tafinlar does not cross the BBB. If anyone can help me formulate the proper questions to ask them when I see them in a few weeks, I'd greatly appreciate the help. If this is worthy of a separate thread, I'll be happy to start one.
Bless,
kali -
- August 28, 2014 at 12:02 am
Probably because the combo drugs aren't really the same as Ipi and PD-1 or PD-L1. For the combo to work, the drugs need access to the tumors, which doesn't happen if it can't cross the BBB. The immunotherapies don't need direct access to the tumors- they need access to your white blood cells, which is much easier to achieve, and the white blood cells can get to brain tumors even if the drug by itself can't. I'm currently on the PD-1 EAP and will have my first round CT and MRI this coming Tuesday. I've had lots of trouble with brain mets (including while on the combo, even though it seemed to work on many of my other body mets) so I'm a bit nervous, but very hopeful that the MRI is at least stable, though I would prefer improved or better yet clear
Best of luck to you
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- August 28, 2014 at 12:02 am
Probably because the combo drugs aren't really the same as Ipi and PD-1 or PD-L1. For the combo to work, the drugs need access to the tumors, which doesn't happen if it can't cross the BBB. The immunotherapies don't need direct access to the tumors- they need access to your white blood cells, which is much easier to achieve, and the white blood cells can get to brain tumors even if the drug by itself can't. I'm currently on the PD-1 EAP and will have my first round CT and MRI this coming Tuesday. I've had lots of trouble with brain mets (including while on the combo, even though it seemed to work on many of my other body mets) so I'm a bit nervous, but very hopeful that the MRI is at least stable, though I would prefer improved or better yet clear
Best of luck to you
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- August 28, 2014 at 12:02 am
Probably because the combo drugs aren't really the same as Ipi and PD-1 or PD-L1. For the combo to work, the drugs need access to the tumors, which doesn't happen if it can't cross the BBB. The immunotherapies don't need direct access to the tumors- they need access to your white blood cells, which is much easier to achieve, and the white blood cells can get to brain tumors even if the drug by itself can't. I'm currently on the PD-1 EAP and will have my first round CT and MRI this coming Tuesday. I've had lots of trouble with brain mets (including while on the combo, even though it seemed to work on many of my other body mets) so I'm a bit nervous, but very hopeful that the MRI is at least stable, though I would prefer improved or better yet clear
Best of luck to you
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- August 28, 2014 at 1:03 pm
Thank you for elaborating. I'm feeling very confused. Are you saying that Mek/Taf is considered combo therapy and not immunotherapy? And that combo drugs don't cross the BBB while immunotherapy meds don't need to? I was under the impression that Mek/Taf is an immunotherapy. And lastly that PD-1, PD-L1, EAP, and Ipi are immunotherapies?
Sorry to keep asking questions but I really want/need to understand this, to help me make the best choices for my treatment.
I hope that your scans bring you the best of news! Thank you again for your help and clarification.
Blessings,
kali -
- August 28, 2014 at 1:03 pm
Thank you for elaborating. I'm feeling very confused. Are you saying that Mek/Taf is considered combo therapy and not immunotherapy? And that combo drugs don't cross the BBB while immunotherapy meds don't need to? I was under the impression that Mek/Taf is an immunotherapy. And lastly that PD-1, PD-L1, EAP, and Ipi are immunotherapies?
Sorry to keep asking questions but I really want/need to understand this, to help me make the best choices for my treatment.
I hope that your scans bring you the best of news! Thank you again for your help and clarification.
Blessings,
kali -
- August 28, 2014 at 1:03 pm
Thank you for elaborating. I'm feeling very confused. Are you saying that Mek/Taf is considered combo therapy and not immunotherapy? And that combo drugs don't cross the BBB while immunotherapy meds don't need to? I was under the impression that Mek/Taf is an immunotherapy. And lastly that PD-1, PD-L1, EAP, and Ipi are immunotherapies?
Sorry to keep asking questions but I really want/need to understand this, to help me make the best choices for my treatment.
I hope that your scans bring you the best of news! Thank you again for your help and clarification.
Blessings,
kali -
- August 28, 2014 at 3:27 pm
Let me try to clarify… right now with melanoma, the two newest innovations in melanoma treatments can be broadly classified into "targeted therapies" and "immunotherapy" (there are other approaches, but these are the biggest breakthroughs and what you're asking about).Targeted therapies do basically what the name implies, they target a unique feature of melanoma cells so that they can attack and destroy tumors without damaging healthy cells. For example, about half of melanoma patients exhibit a genetic mutation in a gene called "BRAF" in their melanoma cells. There is a test for this and for patients who have the mutation ("BRAF positive" or "BRAF+"), and there are drugs called "BRAF inhibitors", like GSK's Tafinlar (dabrafenib) and Roche's Zelboraf (vemurafenib), that can target the mutation. Additionally, there are drugs called "MEK inhibitors", like GSK's Mekinist (trametinib) that also require the BRAF mutation but target a different part of cellular signaling (I won't get into that here) called "MEK", that are now being combined with BRAF inhibitors and have been shown to increase effectiveness, reduce side effects, and prolong the time that the drugs work before resistance. The use of a BRAF inhibitor and MEK inhibitor, most commonly Tafinlar and Mekinist, is one example of a combination therapy, but combination therapies can be the combination of any two drugs really. You might also hear the terms "monotherapy" or "single agent" when referring to any of these drugs being used alone. There are other targeted therapies out there. For melanoma, there are other BRAF and MEK inhibitors in development, but the three mentioned above are those that have received FDA approval as single agents, and, in the case of Tafinlar and Mekinist, as a combination therapy.Immunotherapy is a broad category of any drug or treatment that uses a variety of mechanisms to induce a patient's own immune system to fight cancer. Examples are BMS' Yervoy (ipilimumab) and Opdivo (nivolumab), Merck's pembrolziumab, Interleukin-2 (IL-2, aldesleukin, Proleukin), and Tumor Infiltrating Lymphocytes (TIL). A key difference between these immunotherapies and the targeted therapies is that none of these I've listed directly attack tumors or melanoma cells as do the targeted therapies. Again, they use different ways to modify the immune system, specifically white blood cells or T-cells, so that they, in turn, will attack the cancer. Ipilimumab, nivolumab, and pembrolizumab, can be further grouped into "checkpoint inhibitors". The immune system has a set of natural "brakes" that help keep the immune system from attacking healthy tissues and organs in the body. In the case of these three checkpoint inhibitors, they "take the brakes off" (to an extent) which in some cases will allow the immune system to fight melanoma (with the possible negative side effect of causing other autoimmune-like responses, such as colitis). Ipilimumab targets a protein on T-cells called CTLA-4 and nivolumab and pembrolizumab target a different protein called PD-1. Other immunotherapies like IL-2 and TIL use other means to influence the immune system to fight cancer, but in those examples, too, neither directly attacks tumor cells. Thus far, Yervoy is the only FDA-approved checkpoint inhibitor, although it is expected that pembrolizumab will be approved before the end of October and nivolumab will be submitted for approval very soon, too. There are also trials looking at combinations of immunotherapies that are also refered to as combination therapies. A good example is ipilimumab and nivolumab, but there are others that are looking at combinations of targeted therapies and immunotherapies.Oh, and EAP isn't a drug. It stands for Expanded Access Program, which allows some patients to receive drugs outside of a clinical trial before the drugs have received FDA approval. Currently, Merck has a large EAP running for pembrolizumab, and BMS has one that hasn't been running as long for nivolumab.I hope that helps — hard to balance too much information with too little (I'm sure someone will correct something I wrote above and said I oversimplified something 😉Regards,Joe -
- August 28, 2014 at 4:36 pm
Thank you so much Joe for taking the time to spell this out so clearly. I'm sure a lot of this was explained to me when I was fresh out of brain surgery, but did not sink in. I will read this repeatedly until I have my mind around this before my next appointments in a few weeks.
Again, thank you so much for your time, this is extremely helpful.
Bless,
kali -
- August 28, 2014 at 4:36 pm
Thank you so much Joe for taking the time to spell this out so clearly. I'm sure a lot of this was explained to me when I was fresh out of brain surgery, but did not sink in. I will read this repeatedly until I have my mind around this before my next appointments in a few weeks.
Again, thank you so much for your time, this is extremely helpful.
Bless,
kali -
- August 28, 2014 at 4:36 pm
Thank you so much Joe for taking the time to spell this out so clearly. I'm sure a lot of this was explained to me when I was fresh out of brain surgery, but did not sink in. I will read this repeatedly until I have my mind around this before my next appointments in a few weeks.
Again, thank you so much for your time, this is extremely helpful.
Bless,
kali -
- August 28, 2014 at 3:27 pm
Let me try to clarify… right now with melanoma, the two newest innovations in melanoma treatments can be broadly classified into "targeted therapies" and "immunotherapy" (there are other approaches, but these are the biggest breakthroughs and what you're asking about).Targeted therapies do basically what the name implies, they target a unique feature of melanoma cells so that they can attack and destroy tumors without damaging healthy cells. For example, about half of melanoma patients exhibit a genetic mutation in a gene called "BRAF" in their melanoma cells. There is a test for this and for patients who have the mutation ("BRAF positive" or "BRAF+"), and there are drugs called "BRAF inhibitors", like GSK's Tafinlar (dabrafenib) and Roche's Zelboraf (vemurafenib), that can target the mutation. Additionally, there are drugs called "MEK inhibitors", like GSK's Mekinist (trametinib) that also require the BRAF mutation but target a different part of cellular signaling (I won't get into that here) called "MEK", that are now being combined with BRAF inhibitors and have been shown to increase effectiveness, reduce side effects, and prolong the time that the drugs work before resistance. The use of a BRAF inhibitor and MEK inhibitor, most commonly Tafinlar and Mekinist, is one example of a combination therapy, but combination therapies can be the combination of any two drugs really. You might also hear the terms "monotherapy" or "single agent" when referring to any of these drugs being used alone. There are other targeted therapies out there. For melanoma, there are other BRAF and MEK inhibitors in development, but the three mentioned above are those that have received FDA approval as single agents, and, in the case of Tafinlar and Mekinist, as a combination therapy.Immunotherapy is a broad category of any drug or treatment that uses a variety of mechanisms to induce a patient's own immune system to fight cancer. Examples are BMS' Yervoy (ipilimumab) and Opdivo (nivolumab), Merck's pembrolziumab, Interleukin-2 (IL-2, aldesleukin, Proleukin), and Tumor Infiltrating Lymphocytes (TIL). A key difference between these immunotherapies and the targeted therapies is that none of these I've listed directly attack tumors or melanoma cells as do the targeted therapies. Again, they use different ways to modify the immune system, specifically white blood cells or T-cells, so that they, in turn, will attack the cancer. Ipilimumab, nivolumab, and pembrolizumab, can be further grouped into "checkpoint inhibitors". The immune system has a set of natural "brakes" that help keep the immune system from attacking healthy tissues and organs in the body. In the case of these three checkpoint inhibitors, they "take the brakes off" (to an extent) which in some cases will allow the immune system to fight melanoma (with the possible negative side effect of causing other autoimmune-like responses, such as colitis). Ipilimumab targets a protein on T-cells called CTLA-4 and nivolumab and pembrolizumab target a different protein called PD-1. Other immunotherapies like IL-2 and TIL use other means to influence the immune system to fight cancer, but in those examples, too, neither directly attacks tumor cells. Thus far, Yervoy is the only FDA-approved checkpoint inhibitor, although it is expected that pembrolizumab will be approved before the end of October and nivolumab will be submitted for approval very soon, too. There are also trials looking at combinations of immunotherapies that are also refered to as combination therapies. A good example is ipilimumab and nivolumab, but there are others that are looking at combinations of targeted therapies and immunotherapies.Oh, and EAP isn't a drug. It stands for Expanded Access Program, which allows some patients to receive drugs outside of a clinical trial before the drugs have received FDA approval. Currently, Merck has a large EAP running for pembrolizumab, and BMS has one that hasn't been running as long for nivolumab.I hope that helps — hard to balance too much information with too little (I'm sure someone will correct something I wrote above and said I oversimplified something 😉Regards,Joe -
- August 28, 2014 at 3:27 pm
Let me try to clarify… right now with melanoma, the two newest innovations in melanoma treatments can be broadly classified into "targeted therapies" and "immunotherapy" (there are other approaches, but these are the biggest breakthroughs and what you're asking about).Targeted therapies do basically what the name implies, they target a unique feature of melanoma cells so that they can attack and destroy tumors without damaging healthy cells. For example, about half of melanoma patients exhibit a genetic mutation in a gene called "BRAF" in their melanoma cells. There is a test for this and for patients who have the mutation ("BRAF positive" or "BRAF+"), and there are drugs called "BRAF inhibitors", like GSK's Tafinlar (dabrafenib) and Roche's Zelboraf (vemurafenib), that can target the mutation. Additionally, there are drugs called "MEK inhibitors", like GSK's Mekinist (trametinib) that also require the BRAF mutation but target a different part of cellular signaling (I won't get into that here) called "MEK", that are now being combined with BRAF inhibitors and have been shown to increase effectiveness, reduce side effects, and prolong the time that the drugs work before resistance. The use of a BRAF inhibitor and MEK inhibitor, most commonly Tafinlar and Mekinist, is one example of a combination therapy, but combination therapies can be the combination of any two drugs really. You might also hear the terms "monotherapy" or "single agent" when referring to any of these drugs being used alone. There are other targeted therapies out there. For melanoma, there are other BRAF and MEK inhibitors in development, but the three mentioned above are those that have received FDA approval as single agents, and, in the case of Tafinlar and Mekinist, as a combination therapy.Immunotherapy is a broad category of any drug or treatment that uses a variety of mechanisms to induce a patient's own immune system to fight cancer. Examples are BMS' Yervoy (ipilimumab) and Opdivo (nivolumab), Merck's pembrolziumab, Interleukin-2 (IL-2, aldesleukin, Proleukin), and Tumor Infiltrating Lymphocytes (TIL). A key difference between these immunotherapies and the targeted therapies is that none of these I've listed directly attack tumors or melanoma cells as do the targeted therapies. Again, they use different ways to modify the immune system, specifically white blood cells or T-cells, so that they, in turn, will attack the cancer. Ipilimumab, nivolumab, and pembrolizumab, can be further grouped into "checkpoint inhibitors". The immune system has a set of natural "brakes" that help keep the immune system from attacking healthy tissues and organs in the body. In the case of these three checkpoint inhibitors, they "take the brakes off" (to an extent) which in some cases will allow the immune system to fight melanoma (with the possible negative side effect of causing other autoimmune-like responses, such as colitis). Ipilimumab targets a protein on T-cells called CTLA-4 and nivolumab and pembrolizumab target a different protein called PD-1. Other immunotherapies like IL-2 and TIL use other means to influence the immune system to fight cancer, but in those examples, too, neither directly attacks tumor cells. Thus far, Yervoy is the only FDA-approved checkpoint inhibitor, although it is expected that pembrolizumab will be approved before the end of October and nivolumab will be submitted for approval very soon, too. There are also trials looking at combinations of immunotherapies that are also refered to as combination therapies. A good example is ipilimumab and nivolumab, but there are others that are looking at combinations of targeted therapies and immunotherapies.Oh, and EAP isn't a drug. It stands for Expanded Access Program, which allows some patients to receive drugs outside of a clinical trial before the drugs have received FDA approval. Currently, Merck has a large EAP running for pembrolizumab, and BMS has one that hasn't been running as long for nivolumab.I hope that helps — hard to balance too much information with too little (I'm sure someone will correct something I wrote above and said I oversimplified something 😉Regards,Joe -
- August 27, 2014 at 2:35 pm
Thank you for this perspective, I will certainly bring it to my oncologist. I wonder why he and my radiology oncologist have both told me that one of the reasons I keep developing brain mets is that the Mekinist/Tafinlar does not cross the BBB. If anyone can help me formulate the proper questions to ask them when I see them in a few weeks, I'd greatly appreciate the help. If this is worthy of a separate thread, I'll be happy to start one.
Bless,
kali -
- August 25, 2014 at 6:12 pm
My understanding is that the mechanism of immunotheraputic drugs makes "crossing of the blood brain barrier" realtively unimportant. It is not the ability of the drug to cross the border but that of the immune system to operate on both sides of the border. This is not in doubt. So PD-1 should be as effective in the brain as out because of its influence on the immune system, not because of its presene in the brain.
-
- August 25, 2014 at 6:12 pm
My understanding is that the mechanism of immunotheraputic drugs makes "crossing of the blood brain barrier" realtively unimportant. It is not the ability of the drug to cross the border but that of the immune system to operate on both sides of the border. This is not in doubt. So PD-1 should be as effective in the brain as out because of its influence on the immune system, not because of its presene in the brain.
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