Thanks Multibilly!
Such interesting headlines yesterday. Especially that the financial press (keenly interested in stock prices) is intrigued by what seems to be a "race" for expansion between Bluebird Bio / Celgene and the "dark hose" Nanjing Legend Biotech, which backed the study in China.
I rounded up some additional news stories below for reference. I thought this quote from one of the articles was promising: "'It appears that with this novel immunotherapy, there may be a chance for cure in multiple myeloma,' said Wanhong Zhao, main organizer of the current study on LCAR-B38M and an associate director of hematology at the Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China."
A first: All respond to gene therapy in a blood cancer study
https://apnews.com/119e1d81afe8427a9a04ab1b9ae3c999/A-first:-All-respond-to-gene-therapy-in-a-blood-cancer-study
CAR-T Cancer Approach Has Surprising Success in Multiple Myeloma
http://www.nbcnews.com/health/health-news/car-t-cancer-approach-has-surprising-success-multiple-myeloma-n768516
(I suspect this is the article Rhonda mentioned in her post)
CAR T-Cell therapy sends multiple myeloma into lasting remission
https://www.sciencedaily.com/releases/2017/06/170605110056.htm
Gene-based therapy may thwart a touch cancer
http://health.usnews.com/health-care/articles/2017-06-05/gene-based-therapy-may-thwart-a-tough-blood-cancer
Bluebird Bio shares pop on what CEO calls ‘very exciting’ cancer news
http://www.cnbc.com/2017/06/05/bluebird-bio-shares-pop-on-what-ceo-calls-very-exciting-cancer-news.html
Bluebird, Celgene CAR-T Keeps Multiple Myeloma Patients Relapse Free
https://www.thestreet.com/story/14162047/1/bluebird-celgene-car-t-keeps-multiple-myeloma-patients-relapse-free.html
ASCO dark horse Nanjing Legend Biotech shines with promising CAR-T data
http://www.fiercebiotech.com/biotech/asco-dark-horse-nanjing-legend-biotech-shines-promising-car-t-data
Forums
-
texgal79 - Who do you know with myeloma?: Husband
- When were you/they diagnosed?: 2016
- Age at diagnosis: 43
Re: CAR T-cell therapy for multiple myeloma
Some more great news!
"F.D.A. Panel Recommends Approval for Gene-Altering Leukemia Treatment," The New York Times, July 12, 2017 (link to full text of article)
Excerpts:
A Food and Drug Administration panel opened a new era in medicine on Wednesday, unanimously recommending that the agency approve the first-ever treatment that genetically alters a patient’s own cells to fight cancer, transforming them into what scientists call “a living drug” that powerfully bolsters the immune system to shut down the disease.
If the F.D.A. accepts the recommendation, which is likely, the treatment will be the first gene therapy ever to reach the market. Others are expected: Researchers and drug companies have been engaged in intense competition for decades to reach this milestone. Novartis is now poised to be the first. Its treatment is for a type of leukemia, and it is working on similar types of treatments in hundreds of patients for another form of the disease, as well as multiple myeloma and an aggressive brain tumor.
To use the technique, a separate treatment must be created for each patient — their cells removed at an approved medical center, frozen, shipped to a Novartis plant for thawing and processing, frozen again and shipped back to the treatment center.
A single dose of the resulting product has brought long remissions, and possibly cures, to scores of patients in studies who were facing death because every other treatment had failed. The panel recommended approving the treatment for B-cell acute lymphoblastic leukemia that has resisted treatment, or relapsed, in children and young adults aged 3 to 25 ...
The main evidence that Novartis presented to the F.D.A. came from a study of 63 patients who received the treatment from April 2015 to August 2016. Fifty-two of them, or 82.5 percent, went into remission — a high rate for such a severe disease. Eleven others died ...
At the meeting, the panel of experts did not question the lifesaving potential of the treatment in hopeless cases. But they raised concerns about potentially life-threatening side effects — short-term worries about acute reactions like those Emily experienced, and longer-term worries about whether the infused cells could, years later, cause secondary cancers or other problems.
Oncologists have learned how to treat the acute reactions, and so far, no long-term problems have been detected, but not enough time has passed to rule them out.
Patients who receive the treatment will be entered in a registry and tracked for 15 years.
"F.D.A. Panel Recommends Approval for Gene-Altering Leukemia Treatment," The New York Times, July 12, 2017 (link to full text of article)
Excerpts:
A Food and Drug Administration panel opened a new era in medicine on Wednesday, unanimously recommending that the agency approve the first-ever treatment that genetically alters a patient’s own cells to fight cancer, transforming them into what scientists call “a living drug” that powerfully bolsters the immune system to shut down the disease.
If the F.D.A. accepts the recommendation, which is likely, the treatment will be the first gene therapy ever to reach the market. Others are expected: Researchers and drug companies have been engaged in intense competition for decades to reach this milestone. Novartis is now poised to be the first. Its treatment is for a type of leukemia, and it is working on similar types of treatments in hundreds of patients for another form of the disease, as well as multiple myeloma and an aggressive brain tumor.
To use the technique, a separate treatment must be created for each patient — their cells removed at an approved medical center, frozen, shipped to a Novartis plant for thawing and processing, frozen again and shipped back to the treatment center.
A single dose of the resulting product has brought long remissions, and possibly cures, to scores of patients in studies who were facing death because every other treatment had failed. The panel recommended approving the treatment for B-cell acute lymphoblastic leukemia that has resisted treatment, or relapsed, in children and young adults aged 3 to 25 ...
The main evidence that Novartis presented to the F.D.A. came from a study of 63 patients who received the treatment from April 2015 to August 2016. Fifty-two of them, or 82.5 percent, went into remission — a high rate for such a severe disease. Eleven others died ...
At the meeting, the panel of experts did not question the lifesaving potential of the treatment in hopeless cases. But they raised concerns about potentially life-threatening side effects — short-term worries about acute reactions like those Emily experienced, and longer-term worries about whether the infused cells could, years later, cause secondary cancers or other problems.
Oncologists have learned how to treat the acute reactions, and so far, no long-term problems have been detected, but not enough time has passed to rule them out.
Patients who receive the treatment will be entered in a registry and tracked for 15 years.
Re: CAR T-cell therapy for multiple myeloma
Hi everyone,
The FDA has approved the the Novartis CAR T-cell therapy that until now has usually been referred to as "CTL019". The brand name of the drug will be Kymriah, and it's been approved to treat children and young adults with B-cell ALL [acute lymphoblastic leukemia] that is refractory or has relapsed at least twice.
Just to emphasize, Kymriah has been approved for the treatment of certain leukemia patients. Although the drug has been tested in patients with multiple myeloma, the FDA approved use currently does not include multiple myeloma.
Here's a link to the press release announcing the approval, and here is a lot of the text from the press release:
Novartis receives first ever FDA approval for a CAR-T cell therapy, Kymriah(TM) (CTL019), for children and young adults with B-cell ALL that is refractory or has relapsed at least twice
"At Novartis, we have a long history of being at the forefront of transformative cancer treatment," said Joseph Jimenez, CEO of Novartis. "Five years ago, we began collaborating with the University of Pennsylvania and invested in further developing and bringing what we believed would be a paradigm-changing immunocellular therapy to cancer patients in dire need. With the approval of Kymriah, we are once again delivering on our commitment to change the course of cancer care."
"We are so proud to be part of this historic moment in cancer treatment and are deeply grateful to our researchers, collaborators, and the patients and families who participated in the Kymriah clinical program," said Bruno Strigini, CEO of Novartis Oncology. "As a breakthrough immunocellular therapy for children and young adults who desperately need new options, Kymriah truly embodies our mission to discover new ways to improve patient outcomes and the way cancer is treated."
The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for Kymriah. The REMS program serves to inform and educate healthcare professionals about the risks that may be associated with Kymriah treatment. To support safe patient access, Novartis is establishing a network of certified treatment centers throughout the country which will be fully trained on the use of Kymriah and appropriate patient care.
There has been an urgent need for novel treatment options that improve outcomes for patients with relapsed or refractory (r/r) B-cell precursor ALL, whose prognosis is poor. Patients often undergo multiple treatments including chemotherapy, radiation, targeted therapy or stem cell transplant, yet less than 10% of patients survive five years [2], [3].
Kymriah is an innovative immunocellular therapy that is a one-time treatment. Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence. In 2012, Novartis and the University of Pennsylvania (Penn) entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.
"This therapy is a significant step forward in individualized cancer treatment that may have a tremendous impact on patients' lives," said Carl June, MD, the Richard W. Vague Professor of Immunotherapy, Director of the Center for Cellular Immunotherapies in Penn's Perelman School of Medicine, who is a pioneer of this new treatment. "Through our collaboration with Novartis, we are creating the next wave of immunocellular cancer treatments, and are eager to progress CAR-T therapy in a host of hematologic and other cancer types."
In close collaboration with Novartis and Penn, Children's Hospital of Philadelphia (CHOP) was the first institution to investigate Kymriah in the treatment of pediatric patients leading the single site trial.
"Tisagenlecleucel is the first CAR-T therapy to demonstrate early, deep and durable remission in children and young adults with relapsed or refractory B-cell ALL," said Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at the Perelman School of Medicine at Penn, and Director of the Cancer Immunotherapy Frontier Program at Children's Hospital of Philadelphia (CHOP). "We've never seen anything like this before and I believe this therapy may become the new standard of care for this patient population."
Novartis is committed to ensuring eligible patients have access to Kymriah, and is working to ensure payers understand the value of Kymriah and provide coverage for patients. To address the unique aspects of the therapy, Novartis has also developed various patient access programs to support safe and timely access for patients. Novartis is also providing traditional support to patients by helping them navigate insurance coverage and providing financial assistance for those who are uninsured or underinsured.
Novartis plans additional filings for Kymriah in the US and EU later this year, including applications with the FDA and European Medicines Agency (EMA), for the treatment of adult patients with r/r diffuse large B-cell lymphoma (DLBCL). Additional filings beyond the US and EU are anticipated in 2018.
Groundbreaking Collaboration with the Centers for Medicare and Medicaid Services
Novartis also announced a novel collaboration with the United States Centers for Medicare and Medicaid Services (CMS) focused on improving efficiencies in current regulatory requirements in order to deliver value-based care and ensure access for this specific patient population.
This approach is intended to include indication-based pricing for medicines and supports payments for a medicine, such as Kymriah for its initial indication, based on the clinical outcomes achieved, which would eliminate inefficiencies from the healthcare system. Other value-based approaches related to future indications for Kymriah and CAR-T cell therapies are under discussion.
Furthermore, Novartis is collaborating with CMS to make an outcomes-based approach available to allow for payment only when pediatric and young adult ALL patients respond to Kymriah by the end of the first month. Future potential indications would be reviewed for the most relevant outcomes-based approach.
"Novartis has been at the forefront of outcomes-based pricing and is very pleased to work with CMS on this first-of-its-kind collaboration with a technology that has the potential to transform cancer care," said Joseph Jimenez, CEO of Novartis. "We look forward to continuing to work with CMS to potentially expand this approach to other products and disease states."
About Kymriah Manufacturing
Kymriah will be manufactured for each individual patient using their own cells at the Novartis Morris Plains, New Jersey facility. Novartis has designed a reliable and integrated manufacturing and supply chain platform that allows for an individualized treatment approach on a global scale. This process includes cryopreservation of a patient's harvested (or leukapheresed) cells, giving treating physicians and centers the flexibility to initiate therapy with Kymriah based on the individual patient's condition. Building on our experience, having manufactured CAR-T cells for over 250 patients from 11 countries across various indications, we have demonstrated a reproducible product. Novartis continues to advance its CAR-T manufacturing expertise in Morris Plains, where we have been supplying CAR-T cells for global clinical trials and where we continue to invest in support of the anticipated demand to meet the needs of patients.
Kymriah Pivotal Study Results
The FDA approval of Kymriah is based on the results of the pivotal open-label, multicenter, single-arm Phase II ELIANA trial, the first pediatric global CAR-T cell therapy registration trial examining patients in 25 centers in the US, EU, Canada, Australia and Japan. In this Novartis-sponsored study, 68 patients were infused and 63 were evaluable for efficacy. Results show 83% (52 of 63; 95% confidence interval [CI]: 71%-91%) of patients who received treatment with Kymriah achieved complete remission (CR) or CR with incomplete blood count recovery (CRi) within three months of infusion. In addition, no minimal residual disease (MRD) - a blood marker that indicates potential relapse - was detected among responding patients. Median duration of remission was not reached (95% CI: 7.5-NE) [1].
The most common (>20%) adverse reactions in the ELIANA trial are cytokine release syndrome (CRS), hypogammaglobulinemia, infections-pathogen unspecified, pyrexia, decreased appetite, headache, encephalopathy, hypotension, bleeding episodes, tachycardia, nausea, diarrhea, vomiting, viral infectious disorders, hypoxia, fatigue, acute kidney injury and delirium. In the study, 49% of patients treated with Kymriah experienced grade 3 or 4 CRS, an on-target effect of the treatment that may occur when the engineered cells become activated in the patient's body. CRS was managed globally using prior site education and implementation of the CRS treatment algorithm. Within eight weeks of treatment, 18% of patients experienced grade 3 or 4 neurologic events. There were no incidents of cerebral edema. The most common neurologic events were encephalopathy (34%), headache (37%), delirium (21%), anxiety (13%) and tremor (9%) ...
Kymriah(TM) (tisagenlecleucel) Important Safety information
Kymriah may cause side effects that are fatal or life-threatening, such as Cytokine Release Syndrome (CRS) or Neurological Toxicities. Patients with CRS may experience symptoms including high fever, difficulty breathing, chills/shaking chills, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure or dizziness/lightheadedness. Patients may be admitted to the hospital for CRS and treated with other medications.
Patients with neurological toxicities may experience symptoms such as altered or decreased consciousness, headaches, delirium, confusion, agitation, anxiety, seizures, difficulty speaking and understanding, or loss of balance. Patients should be advised to call their health care provider or get emergency help right away if they experience any of these signs and symptoms of CRS or neurological toxicities.
Because of the risk of CRS and neurological toxicities, Kymriah is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called Kymriah REMS.
Serious allergic reactions, including anaphylaxis, may occur after Kymriah infusion. Kymriah can increase the risk of life-threatening infections that may lead to death. Patients should be advised to tell their health care provider right away if they develop fever, chills, or any signs or symptoms of an infection.
Patients may experience prolonged low blood cell counts (cytopenia), where one or more types of blood cells (red blood cells, white blood cells, or platelets) are decreased. The patient's health care provider will do blood tests to check all of their blood cell counts after treatment with Kymriah. Patients should be advised to tell their health care provider right away if they get a fever, are feeling tired, or have bruising or bleeding.
Patients may experience hypogammaglobulinemia, a condition in which the level of immunoglobulins (antibodies) in the blood is low and the risk of infection is increased. It is expected that patients may develop hypogammaglobulinemia with Kymriah, and may need to receive immunoglobulin replacement for an indefinite amount of time following treatment with Kymriah. Patients should tell their health care provider about their treatment with Kymriah before receiving a live virus vaccine.
After treatment with Kymriah, patients will be monitored life-long by their health care provider, as they may develop secondary cancers or recurrence of their leukemia.
Patients should not drive, operate heavy machinery, or do other dangerous activities for 8 weeks after receiving Kymriah because the treatment can cause temporary memory and coordination problems, including sleepiness, confusion, weakness, dizziness and seizures.
Some of the most common side effects of Kymriah included: difficulty breathing, fever (100.4°F/38°C or higher), chills/shaking chills, confusion, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, and dizziness/lightheadedness. However, these are not all of the possible side effects of Kymriah. Patients should talk to their health care provider for medical advice about side effects.
Prior to a female patient starting treatment with Kymriah, their health care provider may do a pregnancy test. There is no information available for Kymriah use in pregnant or breast-feeding women. Therefore, Kymriah is not recommended for women who are pregnant or breast feeding. If either sex partner has received Kymriah, patients should talk to their health care provider about birth control and pregnancy.
Patients should tell their health care provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
After receiving Kymriah, patients should be advised that some commercial HIV tests may cause a false positive test result. Patients should also be advised not to donate blood, organs, or tissues and cells for transplantation after receiving Kymriah ...
References
[1] Kymriah (tisagenlecleucel) Prescribing information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; August 2017.
[2] Ronson, A., Tvito, A., Rowe, JM., "Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia in Adults." Current Oncology Reports, 2016 Jun;18(6):39.
[3] Leukemia & Lymphoma Society, "Acute Lymphoblastic Leukemia."
[4] National Cancer Institute, "Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®) - Patient Version."
[5] Howlader, N., Noone, A.. M, Krapcho, M., et al. SEER Cancer Statistics Review, 1975-2010. National Cancer Institute, April 2013; Section 28.9 (12).
[6] Oudot, C.., Auclerc, F.., Levy, V., et al. Prognostic Factors for Leukemia Induction Failure in Children With Acute Lymphoblastic Leukemia and Outcome After Salvage Therapy: The FRALLE 93 Study. Journal of Clinical Oncology, March 2008; Volume 28 (9).
[7] Chessels, J., Veys, P., Kempski, H., et al. Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia. British Journal of Hematology, 2003; 123 (3).
[8] Reismuller, B., Peters, C., Dworzak, M., et al. Outcome of children and adolescents with a second or third relapse of acute lymphoblastic leukemia (ALL): a population-based analysis of the Austrian ALL-BFM (Berlin-Frankfurt-Münster) Study Group. Journal of Pediatric Hematology/Oncology. July 2013; 35 (5).
The FDA has approved the the Novartis CAR T-cell therapy that until now has usually been referred to as "CTL019". The brand name of the drug will be Kymriah, and it's been approved to treat children and young adults with B-cell ALL [acute lymphoblastic leukemia] that is refractory or has relapsed at least twice.
Just to emphasize, Kymriah has been approved for the treatment of certain leukemia patients. Although the drug has been tested in patients with multiple myeloma, the FDA approved use currently does not include multiple myeloma.
Here's a link to the press release announcing the approval, and here is a lot of the text from the press release:
Novartis receives first ever FDA approval for a CAR-T cell therapy, Kymriah(TM) (CTL019), for children and young adults with B-cell ALL that is refractory or has relapsed at least twice
- First-in-class therapy showed an 83% (52/63) overall remission rate in this patient population with limited treatment options and historically poor outcomes [1],[2].
- Novel approach to cancer treatment is the result of pioneering CAR-T cell therapy collaboration with University of Pennsylvania
- Reproducible, flexible and validated manufacturing process builds on years of global clinical trial experience at our facility in New Jersey, US
- Novartis also announces innovative collaboration with the US Centers for Medicare and Medicaid Services
"At Novartis, we have a long history of being at the forefront of transformative cancer treatment," said Joseph Jimenez, CEO of Novartis. "Five years ago, we began collaborating with the University of Pennsylvania and invested in further developing and bringing what we believed would be a paradigm-changing immunocellular therapy to cancer patients in dire need. With the approval of Kymriah, we are once again delivering on our commitment to change the course of cancer care."
"We are so proud to be part of this historic moment in cancer treatment and are deeply grateful to our researchers, collaborators, and the patients and families who participated in the Kymriah clinical program," said Bruno Strigini, CEO of Novartis Oncology. "As a breakthrough immunocellular therapy for children and young adults who desperately need new options, Kymriah truly embodies our mission to discover new ways to improve patient outcomes and the way cancer is treated."
The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for Kymriah. The REMS program serves to inform and educate healthcare professionals about the risks that may be associated with Kymriah treatment. To support safe patient access, Novartis is establishing a network of certified treatment centers throughout the country which will be fully trained on the use of Kymriah and appropriate patient care.
There has been an urgent need for novel treatment options that improve outcomes for patients with relapsed or refractory (r/r) B-cell precursor ALL, whose prognosis is poor. Patients often undergo multiple treatments including chemotherapy, radiation, targeted therapy or stem cell transplant, yet less than 10% of patients survive five years [2], [3].
Kymriah is an innovative immunocellular therapy that is a one-time treatment. Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence. In 2012, Novartis and the University of Pennsylvania (Penn) entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.
"This therapy is a significant step forward in individualized cancer treatment that may have a tremendous impact on patients' lives," said Carl June, MD, the Richard W. Vague Professor of Immunotherapy, Director of the Center for Cellular Immunotherapies in Penn's Perelman School of Medicine, who is a pioneer of this new treatment. "Through our collaboration with Novartis, we are creating the next wave of immunocellular cancer treatments, and are eager to progress CAR-T therapy in a host of hematologic and other cancer types."
In close collaboration with Novartis and Penn, Children's Hospital of Philadelphia (CHOP) was the first institution to investigate Kymriah in the treatment of pediatric patients leading the single site trial.
"Tisagenlecleucel is the first CAR-T therapy to demonstrate early, deep and durable remission in children and young adults with relapsed or refractory B-cell ALL," said Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at the Perelman School of Medicine at Penn, and Director of the Cancer Immunotherapy Frontier Program at Children's Hospital of Philadelphia (CHOP). "We've never seen anything like this before and I believe this therapy may become the new standard of care for this patient population."
Novartis is committed to ensuring eligible patients have access to Kymriah, and is working to ensure payers understand the value of Kymriah and provide coverage for patients. To address the unique aspects of the therapy, Novartis has also developed various patient access programs to support safe and timely access for patients. Novartis is also providing traditional support to patients by helping them navigate insurance coverage and providing financial assistance for those who are uninsured or underinsured.
Novartis plans additional filings for Kymriah in the US and EU later this year, including applications with the FDA and European Medicines Agency (EMA), for the treatment of adult patients with r/r diffuse large B-cell lymphoma (DLBCL). Additional filings beyond the US and EU are anticipated in 2018.
Groundbreaking Collaboration with the Centers for Medicare and Medicaid Services
Novartis also announced a novel collaboration with the United States Centers for Medicare and Medicaid Services (CMS) focused on improving efficiencies in current regulatory requirements in order to deliver value-based care and ensure access for this specific patient population.
This approach is intended to include indication-based pricing for medicines and supports payments for a medicine, such as Kymriah for its initial indication, based on the clinical outcomes achieved, which would eliminate inefficiencies from the healthcare system. Other value-based approaches related to future indications for Kymriah and CAR-T cell therapies are under discussion.
Furthermore, Novartis is collaborating with CMS to make an outcomes-based approach available to allow for payment only when pediatric and young adult ALL patients respond to Kymriah by the end of the first month. Future potential indications would be reviewed for the most relevant outcomes-based approach.
"Novartis has been at the forefront of outcomes-based pricing and is very pleased to work with CMS on this first-of-its-kind collaboration with a technology that has the potential to transform cancer care," said Joseph Jimenez, CEO of Novartis. "We look forward to continuing to work with CMS to potentially expand this approach to other products and disease states."
About Kymriah Manufacturing
Kymriah will be manufactured for each individual patient using their own cells at the Novartis Morris Plains, New Jersey facility. Novartis has designed a reliable and integrated manufacturing and supply chain platform that allows for an individualized treatment approach on a global scale. This process includes cryopreservation of a patient's harvested (or leukapheresed) cells, giving treating physicians and centers the flexibility to initiate therapy with Kymriah based on the individual patient's condition. Building on our experience, having manufactured CAR-T cells for over 250 patients from 11 countries across various indications, we have demonstrated a reproducible product. Novartis continues to advance its CAR-T manufacturing expertise in Morris Plains, where we have been supplying CAR-T cells for global clinical trials and where we continue to invest in support of the anticipated demand to meet the needs of patients.
Kymriah Pivotal Study Results
The FDA approval of Kymriah is based on the results of the pivotal open-label, multicenter, single-arm Phase II ELIANA trial, the first pediatric global CAR-T cell therapy registration trial examining patients in 25 centers in the US, EU, Canada, Australia and Japan. In this Novartis-sponsored study, 68 patients were infused and 63 were evaluable for efficacy. Results show 83% (52 of 63; 95% confidence interval [CI]: 71%-91%) of patients who received treatment with Kymriah achieved complete remission (CR) or CR with incomplete blood count recovery (CRi) within three months of infusion. In addition, no minimal residual disease (MRD) - a blood marker that indicates potential relapse - was detected among responding patients. Median duration of remission was not reached (95% CI: 7.5-NE) [1].
The most common (>20%) adverse reactions in the ELIANA trial are cytokine release syndrome (CRS), hypogammaglobulinemia, infections-pathogen unspecified, pyrexia, decreased appetite, headache, encephalopathy, hypotension, bleeding episodes, tachycardia, nausea, diarrhea, vomiting, viral infectious disorders, hypoxia, fatigue, acute kidney injury and delirium. In the study, 49% of patients treated with Kymriah experienced grade 3 or 4 CRS, an on-target effect of the treatment that may occur when the engineered cells become activated in the patient's body. CRS was managed globally using prior site education and implementation of the CRS treatment algorithm. Within eight weeks of treatment, 18% of patients experienced grade 3 or 4 neurologic events. There were no incidents of cerebral edema. The most common neurologic events were encephalopathy (34%), headache (37%), delirium (21%), anxiety (13%) and tremor (9%) ...
Kymriah(TM) (tisagenlecleucel) Important Safety information
Kymriah may cause side effects that are fatal or life-threatening, such as Cytokine Release Syndrome (CRS) or Neurological Toxicities. Patients with CRS may experience symptoms including high fever, difficulty breathing, chills/shaking chills, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure or dizziness/lightheadedness. Patients may be admitted to the hospital for CRS and treated with other medications.
Patients with neurological toxicities may experience symptoms such as altered or decreased consciousness, headaches, delirium, confusion, agitation, anxiety, seizures, difficulty speaking and understanding, or loss of balance. Patients should be advised to call their health care provider or get emergency help right away if they experience any of these signs and symptoms of CRS or neurological toxicities.
Because of the risk of CRS and neurological toxicities, Kymriah is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called Kymriah REMS.
Serious allergic reactions, including anaphylaxis, may occur after Kymriah infusion. Kymriah can increase the risk of life-threatening infections that may lead to death. Patients should be advised to tell their health care provider right away if they develop fever, chills, or any signs or symptoms of an infection.
Patients may experience prolonged low blood cell counts (cytopenia), where one or more types of blood cells (red blood cells, white blood cells, or platelets) are decreased. The patient's health care provider will do blood tests to check all of their blood cell counts after treatment with Kymriah. Patients should be advised to tell their health care provider right away if they get a fever, are feeling tired, or have bruising or bleeding.
Patients may experience hypogammaglobulinemia, a condition in which the level of immunoglobulins (antibodies) in the blood is low and the risk of infection is increased. It is expected that patients may develop hypogammaglobulinemia with Kymriah, and may need to receive immunoglobulin replacement for an indefinite amount of time following treatment with Kymriah. Patients should tell their health care provider about their treatment with Kymriah before receiving a live virus vaccine.
After treatment with Kymriah, patients will be monitored life-long by their health care provider, as they may develop secondary cancers or recurrence of their leukemia.
Patients should not drive, operate heavy machinery, or do other dangerous activities for 8 weeks after receiving Kymriah because the treatment can cause temporary memory and coordination problems, including sleepiness, confusion, weakness, dizziness and seizures.
Some of the most common side effects of Kymriah included: difficulty breathing, fever (100.4°F/38°C or higher), chills/shaking chills, confusion, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, and dizziness/lightheadedness. However, these are not all of the possible side effects of Kymriah. Patients should talk to their health care provider for medical advice about side effects.
Prior to a female patient starting treatment with Kymriah, their health care provider may do a pregnancy test. There is no information available for Kymriah use in pregnant or breast-feeding women. Therefore, Kymriah is not recommended for women who are pregnant or breast feeding. If either sex partner has received Kymriah, patients should talk to their health care provider about birth control and pregnancy.
Patients should tell their health care provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
After receiving Kymriah, patients should be advised that some commercial HIV tests may cause a false positive test result. Patients should also be advised not to donate blood, organs, or tissues and cells for transplantation after receiving Kymriah ...
References
[1] Kymriah (tisagenlecleucel) Prescribing information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; August 2017.
[2] Ronson, A., Tvito, A., Rowe, JM., "Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia in Adults." Current Oncology Reports, 2016 Jun;18(6):39.
[3] Leukemia & Lymphoma Society, "Acute Lymphoblastic Leukemia."
[4] National Cancer Institute, "Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®) - Patient Version."
[5] Howlader, N., Noone, A.. M, Krapcho, M., et al. SEER Cancer Statistics Review, 1975-2010. National Cancer Institute, April 2013; Section 28.9 (12).
[6] Oudot, C.., Auclerc, F.., Levy, V., et al. Prognostic Factors for Leukemia Induction Failure in Children With Acute Lymphoblastic Leukemia and Outcome After Salvage Therapy: The FRALLE 93 Study. Journal of Clinical Oncology, March 2008; Volume 28 (9).
[7] Chessels, J., Veys, P., Kempski, H., et al. Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia. British Journal of Hematology, 2003; 123 (3).
[8] Reismuller, B., Peters, C., Dworzak, M., et al. Outcome of children and adolescents with a second or third relapse of acute lymphoblastic leukemia (ALL): a population-based analysis of the Austrian ALL-BFM (Berlin-Frankfurt-Münster) Study Group. Journal of Pediatric Hematology/Oncology. July 2013; 35 (5).
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JimNY
Re: CAR T-cell therapy for multiple myeloma
Thanks for posting this important information about Car-T cell immunotherapy, Jim NY. I hope that the therapy greatly improves the lives of those suffering from B-cell acute lymophoblastic leukaemia. Maybe the treatment may also be approved for myeloma patients too.
http://www.bbc.com/news/health-41094990
I found an article on the BBC news online which describes this therapy also and hails it as a great advance in medical science!
http://www.bbc.com/news/health-41094990
I found an article on the BBC news online which describes this therapy also and hails it as a great advance in medical science!
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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
Also in CAR T-cell therapy-related news:
Gilead, the biotech company known mainly for its AIDS and hepatitis therapies, has agreed to acquire the biotech company Kite Pharma. This is important because Kite is developing KITE-585, a CAR T-cell therapy for multiple myeloma that targets BCMA. The BCMA target for CAR T-cell therapy seems to be a particularly promising target, as mentioned in a number of the posts earlier in this thread.
Here's a link to the Gilead press release announcing its intended acquisition of KITE.
http://www.gilead.com/news/press-releases/2017/8/gilead-sciences-to-acquire-kite-pharma-for-119-billion
One would expect that Gilead's purchase of KITE would make it easier for development of KITE-585 to move forward quickly, as Gilead should have more funds to devote to development of the drug than KITE would have as a much smaller company.
Gilead, the biotech company known mainly for its AIDS and hepatitis therapies, has agreed to acquire the biotech company Kite Pharma. This is important because Kite is developing KITE-585, a CAR T-cell therapy for multiple myeloma that targets BCMA. The BCMA target for CAR T-cell therapy seems to be a particularly promising target, as mentioned in a number of the posts earlier in this thread.
Here's a link to the Gilead press release announcing its intended acquisition of KITE.
http://www.gilead.com/news/press-releases/2017/8/gilead-sciences-to-acquire-kite-pharma-for-119-billion
One would expect that Gilead's purchase of KITE would make it easier for development of KITE-585 to move forward quickly, as Gilead should have more funds to devote to development of the drug than KITE would have as a much smaller company.
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JimNY
Re: CAR T-cell therapy for multiple myeloma
Anti-BCMA CAR T-cell therapy bb2121 has been granted breakthrough therapy designation by the FDA. Here's a link to the press release announcing the news:
"Celgene Corporation And Bluebird Bio Announce bb2121 Anti-BCMA CAR-T Cell Therapy Has Been Granted Breakthrough Therapy Designation From FDA And Prime Eligibility From EMA For Relapsed And Refractory Multiple Myeloma," Celgene press release, Nov 16, 2017
Excerpts:
Celgene Corporation (NASDAQ:CELG) and bluebird bio, Inc. (NASDAQ:BLUE) today announced that bb2121, a chimeric antigen receptor T-cell (CAR-T) therapy targeting b-cell maturation antigen (BCMA) in previously treated patients with multiple myeloma, has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) and PRIority MEdicines (PRIME) eligibility by the European Medicines Agency (EMA).
BTD designation and PRIME eligibility for bb2121 were based on preliminary clinical data from the ongoing phase 1 study CRB-401. Updated data from CRB-401 is scheduled to be presented at the 59th annual meeting of the American Society of Hematology in Atlanta during an oral presentation on Dec. 11 ...
Breakthrough Therapy Designation is intended to expedite the development and review of drugs that are intended to treat serious or life-threatening conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.
PRIME is a program launched by the EMA to enhance support for the development of medicines that target an unmet medical need. This voluntary program is based on enhanced interaction and early dialogue with developers of promising medicines, to optimize development plans and speed up evaluation so these medicines can reach patients earlier. The program focuses on medicines that may offer a major therapeutic advantage over existing treatments, or benefit patients without treatment options. These medicines are considered priority medicines by EMA. To be accepted for PRIME, a medicine must show its potential to benefit patients with unmet medical needs based on early clinical data.
"Celgene Corporation And Bluebird Bio Announce bb2121 Anti-BCMA CAR-T Cell Therapy Has Been Granted Breakthrough Therapy Designation From FDA And Prime Eligibility From EMA For Relapsed And Refractory Multiple Myeloma," Celgene press release, Nov 16, 2017
Excerpts:
Celgene Corporation (NASDAQ:CELG) and bluebird bio, Inc. (NASDAQ:BLUE) today announced that bb2121, a chimeric antigen receptor T-cell (CAR-T) therapy targeting b-cell maturation antigen (BCMA) in previously treated patients with multiple myeloma, has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) and PRIority MEdicines (PRIME) eligibility by the European Medicines Agency (EMA).
BTD designation and PRIME eligibility for bb2121 were based on preliminary clinical data from the ongoing phase 1 study CRB-401. Updated data from CRB-401 is scheduled to be presented at the 59th annual meeting of the American Society of Hematology in Atlanta during an oral presentation on Dec. 11 ...
Breakthrough Therapy Designation is intended to expedite the development and review of drugs that are intended to treat serious or life-threatening conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.
PRIME is a program launched by the EMA to enhance support for the development of medicines that target an unmet medical need. This voluntary program is based on enhanced interaction and early dialogue with developers of promising medicines, to optimize development plans and speed up evaluation so these medicines can reach patients earlier. The program focuses on medicines that may offer a major therapeutic advantage over existing treatments, or benefit patients without treatment options. These medicines are considered priority medicines by EMA. To be accepted for PRIME, a medicine must show its potential to benefit patients with unmet medical needs based on early clinical data.
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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
Wow! I'd say that's pretty big news. Thanks, Multibilly!
Amazing how these new therapies just keep coming.
Amazing how these new therapies just keep coming.
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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
More data about bb2121; it's still looking very good:
"'Unheard of' responses to bluebird CAR-T therapy seen in myeloma study," Reuters, Dec 10, 2017 (full text of article)
Excerpts from article:
More than half of patients with advanced multiple myeloma who had run out of therapeutic options remained in complete remission after receiving bluebird bio Inc’s experimental gene-modifying immunotherapy in a small, early stage study, according to updated data released on Sunday.
Of 18 patients who received a therapeutic dose of bb2121, all but one responded to the treatment, a 94 percent response rate, while 56 percent remained in remission with a median follow-up of 40 weeks after treatment ...
Patients in the Phase I dose-escalation study had received seven prior treatment regimens, including regimens with the newest multiple myeloma drugs, such as Johnson & Johnson’s Darzalex, and had undergone at least one stem cell transplant before receiving bb2121, which is being co-developed with Celgene Corp ...
Three patients who received what proved to be sub-optimal doses of cells early in the bb2121 study died. Of the 18 who received higher doses, four patients have now experienced disease progression, while 14 continue to respond, researchers reported.
The treatment was very well tolerated for a CAR-T product, Berdeja said.
Only two patients experienced serious cytokine release syndrome with no reports of serious brain toxicity, both common side effects of CAR-T treatment. The most serious side effect was neutropenia, or very low white blood cell count, researchers said.
While this was a small Phase I study, the results were considered so impressive that Celgene plans to begin enrolling patients this month for a larger, potentially pivotal trial that could position bb2121 to become the third approved CAR-T ...
"'Unheard of' responses to bluebird CAR-T therapy seen in myeloma study," Reuters, Dec 10, 2017 (full text of article)
Excerpts from article:
More than half of patients with advanced multiple myeloma who had run out of therapeutic options remained in complete remission after receiving bluebird bio Inc’s experimental gene-modifying immunotherapy in a small, early stage study, according to updated data released on Sunday.
Of 18 patients who received a therapeutic dose of bb2121, all but one responded to the treatment, a 94 percent response rate, while 56 percent remained in remission with a median follow-up of 40 weeks after treatment ...
Patients in the Phase I dose-escalation study had received seven prior treatment regimens, including regimens with the newest multiple myeloma drugs, such as Johnson & Johnson’s Darzalex, and had undergone at least one stem cell transplant before receiving bb2121, which is being co-developed with Celgene Corp ...
Three patients who received what proved to be sub-optimal doses of cells early in the bb2121 study died. Of the 18 who received higher doses, four patients have now experienced disease progression, while 14 continue to respond, researchers reported.
The treatment was very well tolerated for a CAR-T product, Berdeja said.
Only two patients experienced serious cytokine release syndrome with no reports of serious brain toxicity, both common side effects of CAR-T treatment. The most serious side effect was neutropenia, or very low white blood cell count, researchers said.
While this was a small Phase I study, the results were considered so impressive that Celgene plans to begin enrolling patients this month for a larger, potentially pivotal trial that could position bb2121 to become the third approved CAR-T ...
Re: CAR T-cell therapy for multiple myeloma
Thanks, everyone, for all the contributions you've made in this thread.
Because CAR T-cell therapy is now better known and understood within the myeloma community, we are closing down this discussion thread. We encourage forum members, however, to start new threads for questions or information related to specific CAR T-cell therapies. Having threads about specific therapies, rather than one broad CAR T-cell therapy thread, will make it easier for people to find information about those treatments.
Because CAR T-cell therapy is now better known and understood within the myeloma community, we are closing down this discussion thread. We encourage forum members, however, to start new threads for questions or information related to specific CAR T-cell therapies. Having threads about specific therapies, rather than one broad CAR T-cell therapy thread, will make it easier for people to find information about those treatments.
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