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Re: CAR T-cell therapy for multiple myeloma
That's wonderful that you've gotten such a deep response to your ALL (acute lymphocytic leukemia) treatment, Nancy. I've been hoping that you were doing well, so I'm so pleased to hear your news. I hope you respond well to the Velcade. Good luck!
Re: CAR T-cell therapy for multiple myeloma
Thanks for posting this good news about the remission for the acute lymphocytic leukemia, Nancy. I think it is terrific that you were considered for two new clinical trials, but did not need to take them. I hope that the Velcade treatment works really well for the myeloma now also. Best wishes!
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: CAR T-cell therapy for multiple myeloma
Hi NStewart,
Great news that you are in remission from the ALL (acute lymphocytic leukemia). ALL treatment is tough. I have met quite a few ALL patients and everyone mentions how tough the induction therapy was.
I am just curious what types of potential side effects they discussed with respect to Blincyto (blinatumomab). I am sure you know this, but for the others reading that may not know, Blincyto is actually considered a BiTE (bi-specific T-cell engager) as opposed to a "common" antibody like Darzalex or Empliciti. For simplicity, a BiTE is considered between a CAR T cell and an antibody, with the CAR T cell the strongest therapy and the antibody considered the weakest. To give everyone an idea of the difference between a BiTE and an antibody like Darzalex and Empliciti, Blincyto can attain molecular remissions as standalone therapy for relapsed ALL patients. I am really hopeful that adding Blicyto to the current ALL induction will increase the cure rate for adult ALL patients. Is that what the clinical trial they were discussing with you is looking to show?
You wrote:
Sounds like you have a sharp team working for you! Best of luck moving forward.
Mark
Great news that you are in remission from the ALL (acute lymphocytic leukemia). ALL treatment is tough. I have met quite a few ALL patients and everyone mentions how tough the induction therapy was.
I am just curious what types of potential side effects they discussed with respect to Blincyto (blinatumomab). I am sure you know this, but for the others reading that may not know, Blincyto is actually considered a BiTE (bi-specific T-cell engager) as opposed to a "common" antibody like Darzalex or Empliciti. For simplicity, a BiTE is considered between a CAR T cell and an antibody, with the CAR T cell the strongest therapy and the antibody considered the weakest. To give everyone an idea of the difference between a BiTE and an antibody like Darzalex and Empliciti, Blincyto can attain molecular remissions as standalone therapy for relapsed ALL patients. I am really hopeful that adding Blicyto to the current ALL induction will increase the cure rate for adult ALL patients. Is that what the clinical trial they were discussing with you is looking to show?
You wrote:
"Interestingly, for me, when the bone marrow biopsy was done, the sample was tested for the surface antigens on my myeloma cells. I guess that will help my oncologist decide on future treatment based on what antigens the newer drugs target."
Sounds like you have a sharp team working for you! Best of luck moving forward.
Mark
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Mark11
Re: CAR T-cell therapy for multiple myeloma
Mark11-
The possible side effects of the Blincyto haven't been discussed with me, but of course I've been reading up on it. They don't sound fun – neurological complications that are usually reversible being the scariest for me. But most of the drugs we take have scary possible side effects.
What's interesting about Blincyto is that it is a 30-day continuous infusion for each round. During the first round you are hospitalized for 9 days to monitor your reaction to the drug. Then the next round you are hospitalized for 2 days. After that you are hooked up to the portable infusion pump and sent home. I can't remember how many rounds of treatment there are, but it's not too many.
What's encouraging to me with the acute lymphocytic leukemia (ALL) is that the letter my oncologist sent to my primary physician when I was diagnosed with ALL said that my prognosis was guarded. In the latest letter it said that my prognosis was very optimistic. That made me feel so much better.
I'll let you all know what we decide for maintenance when I finish induction for the ALL, I start my next-to-last treatment later this week, and how I'm doing. I've gotten the lab results for my Velcade treatment and the M-spike is beginning to come down.
Nancy in Phila
The possible side effects of the Blincyto haven't been discussed with me, but of course I've been reading up on it. They don't sound fun – neurological complications that are usually reversible being the scariest for me. But most of the drugs we take have scary possible side effects.
What's interesting about Blincyto is that it is a 30-day continuous infusion for each round. During the first round you are hospitalized for 9 days to monitor your reaction to the drug. Then the next round you are hospitalized for 2 days. After that you are hooked up to the portable infusion pump and sent home. I can't remember how many rounds of treatment there are, but it's not too many.
What's encouraging to me with the acute lymphocytic leukemia (ALL) is that the letter my oncologist sent to my primary physician when I was diagnosed with ALL said that my prognosis was guarded. In the latest letter it said that my prognosis was very optimistic. That made me feel so much better.
I'll let you all know what we decide for maintenance when I finish induction for the ALL, I start my next-to-last treatment later this week, and how I'm doing. I've gotten the lab results for my Velcade treatment and the M-spike is beginning to come down.
Nancy in Phila
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NStewart - Name: Nancy Stewart
- Who do you know with myeloma?: self
- When were you/they diagnosed?: 3/08
- Age at diagnosis: 60
Re: CAR T-cell therapy for multiple myeloma
Wow, Nancy! "Guarded" to "very optimistic" is just fantastic. Congratulations!
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Mike F - Name: Mike F
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: May 18, 2012
- Age at diagnosis: 53
Re: CAR T-cell therapy for multiple myeloma
Hi Nancy,
I think I have seen studies that discuss between 2 and 4 cycles for relapsed patients. As a general rule of thumb, immunotherapy can have significant side effects since the human immune system is so powerful. That can be very beneficial or it can be very harmful.
Positive vibes being sent your way that the ALL is a health problem that you will not have to deal with again.
Mark
I think I have seen studies that discuss between 2 and 4 cycles for relapsed patients. As a general rule of thumb, immunotherapy can have significant side effects since the human immune system is so powerful. That can be very beneficial or it can be very harmful.
Positive vibes being sent your way that the ALL is a health problem that you will not have to deal with again.
Mark
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Mark11
Re: CAR T-cell therapy for multiple myeloma
Interesting article with respect to what clinical endpoints are relevant for trials that involve immunotherapy. I have made many of these points in the forum in the past using allogeneic transplant as an example. Immunotherapy typically takes time to show benefit and trials with long term follow up will be necessary to show the benefits of the therapy as opposed to things like "median overall survival at 4 years" like the typical myeloma study looks at.
Here is the beginning of the article:
"Unlike conventional therapies that directly kill tumor cells, immunotherapies harness the patient's own immune system to stimulate a response against the cancer [1]. Immunotherapy includes various treatments with different mechanisms of action, which may involve priming or boosting the immune system, T-cell modulation, natural killer cell activation, reducing immunosuppression and enhancing adaptive immunity. Examples of immunotherapies are hematopoietic stem cell transplantation, cell-based approaches (e.g., T-cell infusion, chimeric antigen receptor T-cell therapy), cancer vaccines (e.g., dendritic cell vaccination, DNA vaccination, peptide vaccination, viral vaccine vectors), immunomodulatory drugs and immuno-oncology agents (including immunostimulatory antibodies), which target immune checkpoints and costimulatory pathways. Immuno-oncology agents exhibit kinetics that are characteristically different from conventional cancer therapies, which involve building a cellular immune response followed by tumor regression. Traditional immunotherapies, such as, IFN and IL-2, have not demonstrated consistent clinical benefit in advanced-stage cancer, possibly due to an incomplete understanding of tumor immunology. Further, the use of conventional trial designs and end points does not capture the novel patterns of response seen with immuno-oncology therapies [2]. Therefore, opportunities to identify effective therapies are potentially being overlooked or not fully appreciated.
The patterns of response to treatment with immuno-oncology agents differ from those seen with conventional therapies [3]. Long-term survival and delayed clinical benefit are common outcomes. Stable disease or responses can occur after conventional progressive disease owing to clinically insignificant new lesions in the presence of other responsive lesions and to a reduction in total tumor burden. As such, discontinuation of immuno-oncology therapies at the first sign of progressive disease might not always be appropriate [4]. In addition, durable stable disease might represent meaningful antitumor activity in patients who do not meet the criteria for an objective response [3]. Because the clinical benefit of immuno-oncology agents might extend beyond that of traditional cytotoxic agents, alternative statistical methods should be considered to allow treatment efficacy of immuno-oncology therapies to be assessed appropriately [3,5]."
Reference:
Hoering, A, et al, "End points and statistical considerations in immuno-oncology trials: impact on multiple myeloma," Future Oncology, April 11, 2017 (full text of article)
Mark
Here is the beginning of the article:
"Unlike conventional therapies that directly kill tumor cells, immunotherapies harness the patient's own immune system to stimulate a response against the cancer [1]. Immunotherapy includes various treatments with different mechanisms of action, which may involve priming or boosting the immune system, T-cell modulation, natural killer cell activation, reducing immunosuppression and enhancing adaptive immunity. Examples of immunotherapies are hematopoietic stem cell transplantation, cell-based approaches (e.g., T-cell infusion, chimeric antigen receptor T-cell therapy), cancer vaccines (e.g., dendritic cell vaccination, DNA vaccination, peptide vaccination, viral vaccine vectors), immunomodulatory drugs and immuno-oncology agents (including immunostimulatory antibodies), which target immune checkpoints and costimulatory pathways. Immuno-oncology agents exhibit kinetics that are characteristically different from conventional cancer therapies, which involve building a cellular immune response followed by tumor regression. Traditional immunotherapies, such as, IFN and IL-2, have not demonstrated consistent clinical benefit in advanced-stage cancer, possibly due to an incomplete understanding of tumor immunology. Further, the use of conventional trial designs and end points does not capture the novel patterns of response seen with immuno-oncology therapies [2]. Therefore, opportunities to identify effective therapies are potentially being overlooked or not fully appreciated.
The patterns of response to treatment with immuno-oncology agents differ from those seen with conventional therapies [3]. Long-term survival and delayed clinical benefit are common outcomes. Stable disease or responses can occur after conventional progressive disease owing to clinically insignificant new lesions in the presence of other responsive lesions and to a reduction in total tumor burden. As such, discontinuation of immuno-oncology therapies at the first sign of progressive disease might not always be appropriate [4]. In addition, durable stable disease might represent meaningful antitumor activity in patients who do not meet the criteria for an objective response [3]. Because the clinical benefit of immuno-oncology agents might extend beyond that of traditional cytotoxic agents, alternative statistical methods should be considered to allow treatment efficacy of immuno-oncology therapies to be assessed appropriately [3,5]."
Reference:
Hoering, A, et al, "End points and statistical considerations in immuno-oncology trials: impact on multiple myeloma," Future Oncology, April 11, 2017 (full text of article)
Mark
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Mark11
Re: CAR T-cell therapy for multiple myeloma
A new and encouraging update on CAR T-cell trial results in China:
http://www.asco.org/about-asco/press-center/news-releases/car-t-cell-therapy-sends-multiple-myeloma-lasting-remission
Key Findings
The authors report results from the first 35 patients with relapsed or treatment-resistant (refractory) multiple myeloma enrolled in this ongoing phase I clinical trial in China. First signs of treatment efficacy appeared as early as 10 days after initial injection of CAR T cells (patients received three split doses of cells over a week). Overall, the objective response rate was 100%, and 33 (94%) patients had an evident clinical remission of myeloma (complete response or very good partial response) within two months of receiving CAR T cells.
To date, 19 patients have been followed for more than four months, a pre-set time for full efficacy assessment by the International Myeloma Working Group (IMWG) consensus. Of the 19 patients, 14 have reached stringent complete response (sCR) criteria, one patient has reached partial response, and four patients have achieved very good partial remission (VgPR) criteria in efficacy.
There has been only a single case of disease progression from VgPR; an extramedullary lesion of the VgPR patient reappeared three months after disappearing on CT scans. There has not been a single case of relapse among patients who reached sCR criteria. The five patients who have been followed for over a year (12-14 months) all remain in sCR status and are free of minimal residual disease as well (have no detectable cancer cells in the bone marrow).
Cytokine release syndrome or CRS, a common and potentially dangerous side effect of CAR T-cell therapy, occurred in 85% of patients, but it was only transient. In the majority of patients symptoms were mild and manageable. CRS is associated with symptoms such as fever, low blood pressure, difficulty breathing, and problems with multiple organs. Only two patients on this study experienced severe CRS (grade 3) but recovered upon receiving tocilizumab (Actemra, an inflammation-reducing treatment commonly used to manage CRS in clinical trials of CAR T-cell therapy). No patients experienced neurologic side effects, another common and serious complication from CAR T-cell therapy.
http://www.asco.org/about-asco/press-center/news-releases/car-t-cell-therapy-sends-multiple-myeloma-lasting-remission
Key Findings
The authors report results from the first 35 patients with relapsed or treatment-resistant (refractory) multiple myeloma enrolled in this ongoing phase I clinical trial in China. First signs of treatment efficacy appeared as early as 10 days after initial injection of CAR T cells (patients received three split doses of cells over a week). Overall, the objective response rate was 100%, and 33 (94%) patients had an evident clinical remission of myeloma (complete response or very good partial response) within two months of receiving CAR T cells.
To date, 19 patients have been followed for more than four months, a pre-set time for full efficacy assessment by the International Myeloma Working Group (IMWG) consensus. Of the 19 patients, 14 have reached stringent complete response (sCR) criteria, one patient has reached partial response, and four patients have achieved very good partial remission (VgPR) criteria in efficacy.
There has been only a single case of disease progression from VgPR; an extramedullary lesion of the VgPR patient reappeared three months after disappearing on CT scans. There has not been a single case of relapse among patients who reached sCR criteria. The five patients who have been followed for over a year (12-14 months) all remain in sCR status and are free of minimal residual disease as well (have no detectable cancer cells in the bone marrow).
Cytokine release syndrome or CRS, a common and potentially dangerous side effect of CAR T-cell therapy, occurred in 85% of patients, but it was only transient. In the majority of patients symptoms were mild and manageable. CRS is associated with symptoms such as fever, low blood pressure, difficulty breathing, and problems with multiple organs. Only two patients on this study experienced severe CRS (grade 3) but recovered upon receiving tocilizumab (Actemra, an inflammation-reducing treatment commonly used to manage CRS in clinical trials of CAR T-cell therapy). No patients experienced neurologic side effects, another common and serious complication from CAR T-cell therapy.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: CAR T-cell therapy for multiple myeloma
Multibilly,
Thanks for posting these trial results.
David
Thanks for posting these trial results.
David
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Arizonan - Name: Arizonan
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: April 2010
- Age at diagnosis: 54
Re: CAR T-cell therapy for multiple myeloma
This is awesome news! There is an article on NBC news today about multiple myeloma and the clinical trial. It also mentions, that multiple myeloma is the second fastest growing cancer for men and third for women, rising 2 to 3 percent per year, according to the National Cancer Institute.
There is hope in the future!
Thanks for sharing.
Rhonda
There is hope in the future!
Thanks for sharing.
Rhonda
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Rhonda - Who do you know with myeloma?: myself
- When were you/they diagnosed?: September 2014
- Age at diagnosis: 54
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