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NATIONAL HARBOR, MD. – .” But, he said, it remains unclear which patients should undergo the procedure.
An especially pressing question is “whether transplant is an alternative to our high-efficacy disease-modifying therapies” (DMTs) in some high-risk patients, Jeffrey A. Cohen, MD, director of experimental therapeutics at Cleveland Clinic’s Mellen Center, said in a presidential lecture at the annual meeting of the Consortium of Multiple Sclerosis Centers.
A handful of ongoing randomized controlled trials will bring answers, he said.
Stem cell therapy exists because there are gaps in MS treatment, Dr. Cohen said. “We have now more than 20 medications. However, none of these therapies is completely effective in all patients. In particular, there are some patients with very active disease who continue to have relapses or new MRI lesion activity despite treatment with all of the available therapies.”
And in progressive MS, the efficacy of a couple of agents is modest and mainly for people with ongoing focal lesion activity, he said. “Finally, all of these currently available therapies are intended primarily to prevent the accumulation of damage, and none of them directly promotes repair. So despite our progress in the field, there still are a number of unmet needs.”
‘Rebooting’ the immune system
Several types of stem cell therapy exist, including remyelination and anti-inflammatory therapy, Dr. Cohen said. In his lecture, he focused on immunoablative or myeloablative therapy followed by autologous hematopoietic stem cell transplantation.
This “complicated, multistep procedure” involves first eliminating the immune system to get rid of pathogenic inflammatory cells. This “big component is actually the therapy for MS. It’s also the step that has the most potential complications,” he said.
According to Dr. Cohen, the next step has been described as “rebooting” the immune system.
Does this procedure help patients with MS? In relapsing MS, reports suggest there’s “almost complete abrogation of disease activity following transplant,” he said, “a benefit that’s lasted 5-10-15 years. In addition, there’s also a benefit on the accumulation of CNS damage as measured by whole brain atrophy.”
Recent data, he said, suggests that MS patients most likely to benefit are young, developed MS relatively recently, are still ambulatory, and have highly active MS despite treatment with first- and second-line agents.
However, there have only been two randomized controlled trials of stem cell transplantation versus DMT, and Dr. Cohen said both studies have limitations. The first one, from 2015, is very small, with just 21 subjects. The second study – from 2019 – is larger (n = 103), but some patients weren’t taking higher-efficacy DMTs.
Other research is more promising: Dr. Cohen highlighted a 2017 analysis that found patients with relapsing/remitting MS who underwent stem-cell transplantation were more likely to be symptom-free at 2 years (78%-83%) than those who took DMTs in clinical trials (13%-46%).
Clinical concerns
As for side effects of stem cell transplantation, Dr. Cohen said, “most patients have some adverse effects during the procedure itself. There may be an MS relapse or pseudorelapses in association with the mobilization and the conditioning regimens.”
A wide range of other adverse effects is possible before the immune system is reconstituted, he said, including reactivation of various virus infections, such as HPV, CMV or EPV (Epstein-Barr virus), secondary autoimmune phenomenon, and secondary malignancy. EPV infection is also common after transplant, and is “probably the most troublesome posttransplant complication from a management point of view,” he said.
“Thankfully, once the patient ... recovers from the transplant procedure, late adverse effects are relatively uncommon, the most common of which would be infertility,” he said. “There have been some reports of successful pregnancies following transplant, but it’s important to advise people who are considering transplant that most men and women have infertility after the procedure. So if they desire to have children afterward, they need to be counseled on necessary preparations to do that.”
What about progressive multifocal leukoencephalopathy (PML), which seems a possible risk because of the suppression of the immune system? Dr. Cohen is aware of one case linked to a stem-cell transplant, and it may not have been caused by the procedure.
Cost is another potential obstacle, he noted. The National Multiple Sclerosis Society estimates that autologous hematopoietic stem cell transplants cost $150,000 on average in the U.S., although the expense varies widely.
Unanswered questions
Moving forward, Dr. Cohen said it remains unclear how these procedures fare against the newest generations of DMTs in MS. Five phase 3 randomized controlled trials are now trying to clarify the matter, he said, by pitting stem-cell transplantation against various MS drugs – alemtuzumab, cladribine, natalizumab, ocrelizumab, and rituximab.
There are also unanswered questions about the best conditioning regimens in the transplants, he said, and lack of clarity about where to draw the line between eligible and ineligible patients with MS. “How many DMTs does the person have to fail? What’s the upper level of disability beyond which it is unlikely to be helpful and more likely to cause harm?”
He added: “A particular profile that we’re seeing increasingly at our center is someone with very active disease and onset who gets started on a high-efficacy therapy as their first therapy and effectively stops relapses and MRI lesion activity. But within a couple of years, we can tell that they’re already starting to accumulate disability. Is this someone for whom transplant might be useful, and by extension, is transplant appropriate as the first therapy in some patients? And beyond MS, is transplant a consideration for other autoimmune CNS disorders? There are lots of unanswered questions, which future studies will hopefully begin to address.”
Dr. Cohen reports consulting for Biogen, Bristol‐Myers Squibb, Convelo, EMD Serono, GlaxoSmithKline (now GSK), Janssen, Mylan, and PSI. He serves as an editor of Multiple Sclerosis Journal.
NATIONAL HARBOR, MD. – .” But, he said, it remains unclear which patients should undergo the procedure.
An especially pressing question is “whether transplant is an alternative to our high-efficacy disease-modifying therapies” (DMTs) in some high-risk patients, Jeffrey A. Cohen, MD, director of experimental therapeutics at Cleveland Clinic’s Mellen Center, said in a presidential lecture at the annual meeting of the Consortium of Multiple Sclerosis Centers.
A handful of ongoing randomized controlled trials will bring answers, he said.
Stem cell therapy exists because there are gaps in MS treatment, Dr. Cohen said. “We have now more than 20 medications. However, none of these therapies is completely effective in all patients. In particular, there are some patients with very active disease who continue to have relapses or new MRI lesion activity despite treatment with all of the available therapies.”
And in progressive MS, the efficacy of a couple of agents is modest and mainly for people with ongoing focal lesion activity, he said. “Finally, all of these currently available therapies are intended primarily to prevent the accumulation of damage, and none of them directly promotes repair. So despite our progress in the field, there still are a number of unmet needs.”
‘Rebooting’ the immune system
Several types of stem cell therapy exist, including remyelination and anti-inflammatory therapy, Dr. Cohen said. In his lecture, he focused on immunoablative or myeloablative therapy followed by autologous hematopoietic stem cell transplantation.
This “complicated, multistep procedure” involves first eliminating the immune system to get rid of pathogenic inflammatory cells. This “big component is actually the therapy for MS. It’s also the step that has the most potential complications,” he said.
According to Dr. Cohen, the next step has been described as “rebooting” the immune system.
Does this procedure help patients with MS? In relapsing MS, reports suggest there’s “almost complete abrogation of disease activity following transplant,” he said, “a benefit that’s lasted 5-10-15 years. In addition, there’s also a benefit on the accumulation of CNS damage as measured by whole brain atrophy.”
Recent data, he said, suggests that MS patients most likely to benefit are young, developed MS relatively recently, are still ambulatory, and have highly active MS despite treatment with first- and second-line agents.
However, there have only been two randomized controlled trials of stem cell transplantation versus DMT, and Dr. Cohen said both studies have limitations. The first one, from 2015, is very small, with just 21 subjects. The second study – from 2019 – is larger (n = 103), but some patients weren’t taking higher-efficacy DMTs.
Other research is more promising: Dr. Cohen highlighted a 2017 analysis that found patients with relapsing/remitting MS who underwent stem-cell transplantation were more likely to be symptom-free at 2 years (78%-83%) than those who took DMTs in clinical trials (13%-46%).
Clinical concerns
As for side effects of stem cell transplantation, Dr. Cohen said, “most patients have some adverse effects during the procedure itself. There may be an MS relapse or pseudorelapses in association with the mobilization and the conditioning regimens.”
A wide range of other adverse effects is possible before the immune system is reconstituted, he said, including reactivation of various virus infections, such as HPV, CMV or EPV (Epstein-Barr virus), secondary autoimmune phenomenon, and secondary malignancy. EPV infection is also common after transplant, and is “probably the most troublesome posttransplant complication from a management point of view,” he said.
“Thankfully, once the patient ... recovers from the transplant procedure, late adverse effects are relatively uncommon, the most common of which would be infertility,” he said. “There have been some reports of successful pregnancies following transplant, but it’s important to advise people who are considering transplant that most men and women have infertility after the procedure. So if they desire to have children afterward, they need to be counseled on necessary preparations to do that.”
What about progressive multifocal leukoencephalopathy (PML), which seems a possible risk because of the suppression of the immune system? Dr. Cohen is aware of one case linked to a stem-cell transplant, and it may not have been caused by the procedure.
Cost is another potential obstacle, he noted. The National Multiple Sclerosis Society estimates that autologous hematopoietic stem cell transplants cost $150,000 on average in the U.S., although the expense varies widely.
Unanswered questions
Moving forward, Dr. Cohen said it remains unclear how these procedures fare against the newest generations of DMTs in MS. Five phase 3 randomized controlled trials are now trying to clarify the matter, he said, by pitting stem-cell transplantation against various MS drugs – alemtuzumab, cladribine, natalizumab, ocrelizumab, and rituximab.
There are also unanswered questions about the best conditioning regimens in the transplants, he said, and lack of clarity about where to draw the line between eligible and ineligible patients with MS. “How many DMTs does the person have to fail? What’s the upper level of disability beyond which it is unlikely to be helpful and more likely to cause harm?”
He added: “A particular profile that we’re seeing increasingly at our center is someone with very active disease and onset who gets started on a high-efficacy therapy as their first therapy and effectively stops relapses and MRI lesion activity. But within a couple of years, we can tell that they’re already starting to accumulate disability. Is this someone for whom transplant might be useful, and by extension, is transplant appropriate as the first therapy in some patients? And beyond MS, is transplant a consideration for other autoimmune CNS disorders? There are lots of unanswered questions, which future studies will hopefully begin to address.”
Dr. Cohen reports consulting for Biogen, Bristol‐Myers Squibb, Convelo, EMD Serono, GlaxoSmithKline (now GSK), Janssen, Mylan, and PSI. He serves as an editor of Multiple Sclerosis Journal.
NATIONAL HARBOR, MD. – .” But, he said, it remains unclear which patients should undergo the procedure.
An especially pressing question is “whether transplant is an alternative to our high-efficacy disease-modifying therapies” (DMTs) in some high-risk patients, Jeffrey A. Cohen, MD, director of experimental therapeutics at Cleveland Clinic’s Mellen Center, said in a presidential lecture at the annual meeting of the Consortium of Multiple Sclerosis Centers.
A handful of ongoing randomized controlled trials will bring answers, he said.
Stem cell therapy exists because there are gaps in MS treatment, Dr. Cohen said. “We have now more than 20 medications. However, none of these therapies is completely effective in all patients. In particular, there are some patients with very active disease who continue to have relapses or new MRI lesion activity despite treatment with all of the available therapies.”
And in progressive MS, the efficacy of a couple of agents is modest and mainly for people with ongoing focal lesion activity, he said. “Finally, all of these currently available therapies are intended primarily to prevent the accumulation of damage, and none of them directly promotes repair. So despite our progress in the field, there still are a number of unmet needs.”
‘Rebooting’ the immune system
Several types of stem cell therapy exist, including remyelination and anti-inflammatory therapy, Dr. Cohen said. In his lecture, he focused on immunoablative or myeloablative therapy followed by autologous hematopoietic stem cell transplantation.
This “complicated, multistep procedure” involves first eliminating the immune system to get rid of pathogenic inflammatory cells. This “big component is actually the therapy for MS. It’s also the step that has the most potential complications,” he said.
According to Dr. Cohen, the next step has been described as “rebooting” the immune system.
Does this procedure help patients with MS? In relapsing MS, reports suggest there’s “almost complete abrogation of disease activity following transplant,” he said, “a benefit that’s lasted 5-10-15 years. In addition, there’s also a benefit on the accumulation of CNS damage as measured by whole brain atrophy.”
Recent data, he said, suggests that MS patients most likely to benefit are young, developed MS relatively recently, are still ambulatory, and have highly active MS despite treatment with first- and second-line agents.
However, there have only been two randomized controlled trials of stem cell transplantation versus DMT, and Dr. Cohen said both studies have limitations. The first one, from 2015, is very small, with just 21 subjects. The second study – from 2019 – is larger (n = 103), but some patients weren’t taking higher-efficacy DMTs.
Other research is more promising: Dr. Cohen highlighted a 2017 analysis that found patients with relapsing/remitting MS who underwent stem-cell transplantation were more likely to be symptom-free at 2 years (78%-83%) than those who took DMTs in clinical trials (13%-46%).
Clinical concerns
As for side effects of stem cell transplantation, Dr. Cohen said, “most patients have some adverse effects during the procedure itself. There may be an MS relapse or pseudorelapses in association with the mobilization and the conditioning regimens.”
A wide range of other adverse effects is possible before the immune system is reconstituted, he said, including reactivation of various virus infections, such as HPV, CMV or EPV (Epstein-Barr virus), secondary autoimmune phenomenon, and secondary malignancy. EPV infection is also common after transplant, and is “probably the most troublesome posttransplant complication from a management point of view,” he said.
“Thankfully, once the patient ... recovers from the transplant procedure, late adverse effects are relatively uncommon, the most common of which would be infertility,” he said. “There have been some reports of successful pregnancies following transplant, but it’s important to advise people who are considering transplant that most men and women have infertility after the procedure. So if they desire to have children afterward, they need to be counseled on necessary preparations to do that.”
What about progressive multifocal leukoencephalopathy (PML), which seems a possible risk because of the suppression of the immune system? Dr. Cohen is aware of one case linked to a stem-cell transplant, and it may not have been caused by the procedure.
Cost is another potential obstacle, he noted. The National Multiple Sclerosis Society estimates that autologous hematopoietic stem cell transplants cost $150,000 on average in the U.S., although the expense varies widely.
Unanswered questions
Moving forward, Dr. Cohen said it remains unclear how these procedures fare against the newest generations of DMTs in MS. Five phase 3 randomized controlled trials are now trying to clarify the matter, he said, by pitting stem-cell transplantation against various MS drugs – alemtuzumab, cladribine, natalizumab, ocrelizumab, and rituximab.
There are also unanswered questions about the best conditioning regimens in the transplants, he said, and lack of clarity about where to draw the line between eligible and ineligible patients with MS. “How many DMTs does the person have to fail? What’s the upper level of disability beyond which it is unlikely to be helpful and more likely to cause harm?”
He added: “A particular profile that we’re seeing increasingly at our center is someone with very active disease and onset who gets started on a high-efficacy therapy as their first therapy and effectively stops relapses and MRI lesion activity. But within a couple of years, we can tell that they’re already starting to accumulate disability. Is this someone for whom transplant might be useful, and by extension, is transplant appropriate as the first therapy in some patients? And beyond MS, is transplant a consideration for other autoimmune CNS disorders? There are lots of unanswered questions, which future studies will hopefully begin to address.”
Dr. Cohen reports consulting for Biogen, Bristol‐Myers Squibb, Convelo, EMD Serono, GlaxoSmithKline (now GSK), Janssen, Mylan, and PSI. He serves as an editor of Multiple Sclerosis Journal.
At CMSC 2022