New Research on PD-1 and Brain Mets

I should qualify my original post by saying that it's light on details of how they're planning to continue their trials and research, but Dr. Jilaveanu mentioned in the brief article is, I assume, a colleague of Dr. Sznol at Yale, who I believe has been a proponent of moving forward with clarifying the role and benefit of the checkpoint inhibitors, anti-PD-1 included, for patients with brain metastases.  He's certainly not the only one, as Celeste mentions, Dr. Weber (among others) at Moffitt, has been trying to move it into practice.  It's encouraging to see.

From my read of the landscape, I think a lot has been learned from the safety side, understandably important for brain mets — bleeding, swelling, etc. during treatment are especially troublesome for brain mets.  But it would seem that most of the new therapies, targeted (BRAF/MEK) and checkpoint inhibitors (ipi/nivo/pembro) are showing a decent safety profile with patients with brain mets.  Even some of the more physically challenging treatment protocols are relaxing the eligibility requirements.  When I had TIL three years ago, brain mets made patients ineligible — more so because of the IL-2 that goes along with TIL and the mental status changes IL-2 for which is already infamous — but now, controlled brain mets are not an automatic disqualification.

Now that there's more comfort with the safety, it's time to take a hard look at efficacy and push to make these treatments available to patients who are presenting with brain metastases.  The science supports that they (especially the checkpoint inhibitors) should be as effective in treating a brain met as in treating any other met, simply because the medication itself doesn't need to reach the tumor site through the blood-brain barrier, only prompt an immune response to the site, which happens externally to the tumor site and the immune system is active in the brain.  It also seems that the targeted BRAF/MEK drugs are also showing effectiveness.  Granted, brain mets can require a more immediate response because of the dangers they pose, which doesn't always allow time for a sometimes delayed response by ipi, nivo, or pembro, but that's where a multi-pronged approach of radiation or BRAF/MEK inhibition in parallel with or followed by a checkpoint inhibitor can come into play.

My two cents — like I said, it's just encouraging to see more focus on the newer treatments given to what is, unfortunately, an all-to-common complication for many who are fighting Stage IV metastatic melanoma.

Best, Joe

I should qualify my original post by saying that it's light on details of how they're planning to continue their trials and research, but Dr. Jilaveanu mentioned in the brief article is, I assume, a colleague of Dr. Sznol at Yale, who I believe has been a proponent of moving forward with clarifying the role and benefit of the checkpoint inhibitors, anti-PD-1 included, for patients with brain metastases.  He's certainly not the only one, as Celeste mentions, Dr. Weber (among others) at Moffitt, has been trying to move it into practice.  It's encouraging to see.

From my read of the landscape, I think a lot has been learned from the safety side, understandably important for brain mets — bleeding, swelling, etc. during treatment are especially troublesome for brain mets.  But it would seem that most of the new therapies, targeted (BRAF/MEK) and checkpoint inhibitors (ipi/nivo/pembro) are showing a decent safety profile with patients with brain mets.  Even some of the more physically challenging treatment protocols are relaxing the eligibility requirements.  When I had TIL three years ago, brain mets made patients ineligible — more so because of the IL-2 that goes along with TIL and the mental status changes IL-2 for which is already infamous — but now, controlled brain mets are not an automatic disqualification.

Now that there's more comfort with the safety, it's time to take a hard look at efficacy and push to make these treatments available to patients who are presenting with brain metastases.  The science supports that they (especially the checkpoint inhibitors) should be as effective in treating a brain met as in treating any other met, simply because the medication itself doesn't need to reach the tumor site through the blood-brain barrier, only prompt an immune response to the site, which happens externally to the tumor site and the immune system is active in the brain.  It also seems that the targeted BRAF/MEK drugs are also showing effectiveness.  Granted, brain mets can require a more immediate response because of the dangers they pose, which doesn't always allow time for a sometimes delayed response by ipi, nivo, or pembro, but that's where a multi-pronged approach of radiation or BRAF/MEK inhibition in parallel with or followed by a checkpoint inhibitor can come into play.

My two cents — like I said, it's just encouraging to see more focus on the newer treatments given to what is, unfortunately, an all-to-common complication for many who are fighting Stage IV metastatic melanoma.

Best, Joe

I should qualify my original post by saying that it's light on details of how they're planning to continue their trials and research, but Dr. Jilaveanu mentioned in the brief article is, I assume, a colleague of Dr. Sznol at Yale, who I believe has been a proponent of moving forward with clarifying the role and benefit of the checkpoint inhibitors, anti-PD-1 included, for patients with brain metastases.  He's certainly not the only one, as Celeste mentions, Dr. Weber (among others) at Moffitt, has been trying to move it into practice.  It's encouraging to see.

From my read of the landscape, I think a lot has been learned from the safety side, understandably important for brain mets — bleeding, swelling, etc. during treatment are especially troublesome for brain mets.  But it would seem that most of the new therapies, targeted (BRAF/MEK) and checkpoint inhibitors (ipi/nivo/pembro) are showing a decent safety profile with patients with brain mets.  Even some of the more physically challenging treatment protocols are relaxing the eligibility requirements.  When I had TIL three years ago, brain mets made patients ineligible — more so because of the IL-2 that goes along with TIL and the mental status changes IL-2 for which is already infamous — but now, controlled brain mets are not an automatic disqualification.

Now that there's more comfort with the safety, it's time to take a hard look at efficacy and push to make these treatments available to patients who are presenting with brain metastases.  The science supports that they (especially the checkpoint inhibitors) should be as effective in treating a brain met as in treating any other met, simply because the medication itself doesn't need to reach the tumor site through the blood-brain barrier, only prompt an immune response to the site, which happens externally to the tumor site and the immune system is active in the brain.  It also seems that the targeted BRAF/MEK drugs are also showing effectiveness.  Granted, brain mets can require a more immediate response because of the dangers they pose, which doesn't always allow time for a sometimes delayed response by ipi, nivo, or pembro, but that's where a multi-pronged approach of radiation or BRAF/MEK inhibition in parallel with or followed by a checkpoint inhibitor can come into play.

My two cents — like I said, it's just encouraging to see more focus on the newer treatments given to what is, unfortunately, an all-to-common complication for many who are fighting Stage IV metastatic melanoma.

Best, Joe