Off to the CAR T Races: Bringing CAR T-Cell Therapies to Cancer Patients

August 30, 2017, marked a milestone for medicine: The cell-based gene therapy tisagenlecleucel became the first U.S. Food and Drug Administration (FDA)–approved treatment that re-engineers a patient’s own T cells into focused cancer killers.1

The decision followed the FDA’s Oncologic Drugs Advisory Committee’s unanimous vote to recommend the immunotherapy for approval; in remarks, one panel member called it the “most exciting thing I’ve seen in my lifetime.”2

This approval “marks an important shift in the blood cancer treatment paradigm,” commented Kenneth Anderson, MD, president of the American Society of Hematology (ASH), in a press release. “We now have proof that it is possible to eradicate cancer by harnessing the power of a patient’s own immune system.”3

Less than two months later, tisagenlecleucel was joined by another CAR T-cell therapy: Axicabtagene ciloleucel was approved for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy.4

Breakthrough treatments inevitably raise challenging issues, and chimeric antigen receptor (CAR) T-cell therapies are no exception. ASH Clinical News spoke with scientists and clinicians to better understand the science, potential, and most pressing issues surrounding CAR T-cell therapies.

“We now have proof that it is possible to eradicate cancer by harnessing the power of a patient’s own immune system.”

—Kenneth Anderson, MD

A First-in-Class Approval

A quick primer on CAR T-cell therapies: A patient’s T cells are harvested, re-engineered to express a recombinant receptor that targets a tumor-specific protein, and infused back into the patient’s body to proliferate and eradicate cancer cells.

The concept of “training” T cells to hunt and destroy cancer cells is the stuff of dreams for scientists who have spent their careers trying to take advantage of the innate immune system to combat disease. With the approval of the first CAR T-cell treatment, albeit for a discrete indication, that dream becomes a reality.

Pharmaceutical companies are racing to bring their candidate products to market. With the approval of tisagenlecleucel, Novartis was the first to reach the proverbial finish line. (For a look at the other companies and therapies attempting to follow in its tracks, see the SIDEBAR.)

Tisagenlecleucel (formerly known as CTL019 and branded as Kymriah) was developed by researchers at the University of Pennsylvania to use the 4-1BB costimulatory domain to enhance cellular responses. It is indicated for the treatment of children and young adults with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.

ALL is the most common childhood cancer, and relapsed ALL is a leading cause of cancer death in children. However, five-year survival for children and adolescents has increased over time and is now estimated at 85 percent.5 For all the hype surrounding its approval, tisagenlecleucel is only approved for that small percentage who relapse. In the most recent data from the pivotal phase III ELIANA study, 83 percent of patients who received tisagenlecleucel achieved complete remission (CR) or CR with incomplete blood count recovery within three months.6

“Obviously, for the patients who need the therapy, the impact is great,” said Navneet Majhail, MBBS, MD, director of the Blood and Marrow Transplant Program at Cleveland Clinic’s Taussig Cancer Institute in Ohio. However, he added, “the larger, societal impact is going to be relatively small.”

Novartis plans additional filings for tisagenlecleucel in the U.S. and the European Union later this year, including an application for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), based on interim results from the phase II JULIET study. At three-month follow-up, the overall response rate in adults with relapsed or refractory DLBCL was less than half what was seen for children with ALL – 45 percent – with 37 percent of patients achieving CR.7

The company is actively studying other CAR T-cell therapies, including CTL119, a humanized anti-CD19 CAR in early development for multiple B-cell malignancies, as well as CAR T-cell therapies for myeloid leukemias, multiple myeloma, and solid tumors.

Rolling Out CAR Ts Worldwide

When the FDA announced its decision on tisagenlecleucel, Novartis introduced a new pricing model and reimbursement plan for the product. The company is also busy establishing a network of treatment centers slated to include 32 fully certified centers by the end of 2017. Only designated centers will be permitted to collect cells for tisagenlecleucel manufacturing and subsequently prescribe the product.

Dr. Majhail’s center, which was not part of the ELIANA trial but has participated in other CAR-T trials, is in the process of being approved to administer tisagenlecleucel as a commercial product.

As a transplant center that performs approximately 200 bone marrow (BM) transplants each year, he expects it to “easily accommodate” patients requiring CAR T-cell treatment. However, he suspects the complexity of the entire therapeutic process might make it difficult for non-transplant centers to become CAR T-cell providers.

“Obviously, for the patients who need the therapy, the impact is great. The larger, societal impact is going to be relatively small.”

—Navneet Majhail, MBBS, MD

“Conceptually, the process [of manufacturing and administering CAR T-cell therapy] is like a BM transplant: You have to ensure the patient is a candidate, collect the T cells by apheresis, work with the cell-processing lab to send them to a production facility, receive them back, administer lymphodepleting chemotherapy, infuse the patients, and provide post-infusion care, including preventing and treating complications. All these processes are essentially what we do in BM transplantation right now.”

Manufacturing Marvels

Manufacturing CAR T-cell therapies is no simple feat, requiring several carefully executed steps. “These products must be temperature-controlled at all times during preparation, shipping, and administration, and can only be manipulated under aseptic conditions,” explained Marcela V. Maus, MD, PhD, of the Massachusetts General Hospital, and Sarah Nikiforow, MD, PhD, of the Dana-Farber Cancer Institute, in a recent paper published in the Journal for ImmunoTherapy of Cancer.8

Drs. Maus and Nikiforow (a 2014 ASH Scholar Award recipient) are members of the Foundation for the Accreditation of Cellular Therapy, an organization established by the International Society for Cellular Therapy and the American Society of Blood and Marrow Transplantation for voluntary inspection and accreditation in the field of cellular therapy. The agency established new standards for the use of immune effector cells, specifying the clinical and quality infrastructure required for safe administration of those therapies.

In the early days of tisagenlecleucel, cell processing was performed at the University of Pennsylvania, the academic center where it was developed. Once tisagenlecleucel advanced to later-phase trials, Novartis transferred manufacturing to their facility in Morris Plains, New Jersey; to date, more than 250 patients in 11 countries across various indications have received T-cell products manufactured at the Novartis site.9

The manufacturing process includes cryopreservation of a patient’s harvested cells, giving treating physicians and centers greater flexibility to initiate CAR T-cell therapy based on the individual patient’s condition.

“Cryopreservation also allows for manufacturing and treatment of patients from around the world,” according to the pharmaceutical company, which also has a manufacturing facility in Leipzig, Germany.

Manufacturing failure does happen. In the most recent data on tisagenlecleucel, seven of 88 patients (8%) enrolled in the trial were not infused as a result of insufficiently formulated CAR T-cell product.5 Early reported manufacturing failure rates in hematology/oncology studies using several different CAR T-cell products ranged from 2 percent to 14 percent.10

The most common reason for manufacturing failure was “inability to achieve targeted dose,” most commonly caused by an inadequate number of T cells in the incoming apheresed product, poor selection of T cells on day zero of manufacturing, or irreversibly impaired T cells (i.e., no response to stimulation in culture). In addition, more general causes, such as microbial contamination, equipment-related cell loss, high endotoxin level, and accidents, can ruin CAR T-cell products for clinical use.

“We have much more difficulty growing these cells in culture with certain diseases, and that is usually related to the amount of prior therapy that the patients have received,” Adrian P. Gee, PhD, professor in the Department of Pediatrics, Section of Hematology-Oncology at Baylor College of Medicine in Houston, Texas, told ASH Clinical News. Indeed, the cited 14 percent failure rate was seen in an early study that enrolled heavily treated lymphoma patients.

Dr. Gee also directs the Clinical Applications Laboratory and the Cell Processing and Vector Production Core Laboratory at the Center for Cell and Gene Therapy at Baylor, which is conducting preclinical and early clinical research in CAR T cells for multiple indications, including neuroblastoma. They produce their own de novo CAR T cells in their facility.

One sure way to simplify and more readily scale up manufacturing is to develop an “off-the-shelf” allogeneic CAR T-cell product that uses immune cells from a healthy donor. It would be “very attractive to just generate the cells from healthy donors, and then they’d be immediately available to treat a patient,” said Dr. Gee.

This process also would eliminate the time and costs involved in production: Allogeneic products could potentially be manufactured in bulk, ready to use whenever a patient needs them. Experimental allogeneic CAR T-cells are being evaluated in clinical trials but have shown little success. On September 4, Cellectis reported that the FDA had placed a clinical hold on its phase II studies of UCART23 in patients with blastic plasmacytoid dendritic cell neoplasm and acute myeloid leukemia following a patient death after the development of cytokine release syndrome (CRS) and lung infection.11 A potential explanation for the severity of CRS in that patient is that T cells from healthy donors may be more potent than those from sick patients. The company is working with the investigators and the FDA to resume the trials with an amended protocol.

When the Cure Creates a Disease

Sending a patient’s own T cells to boot camp may seem relatively innocuous, but safety issues have plagued the development of this revolutionary approach. Several other trials have been delayed or halted due to patient deaths, and numerous investigational CAR T-cell products have been abandoned because of toxicities.

The adverse events (AEs) commonly associated with CAR T-cell therapy – tumor lysis syndrome, neurotoxicity, and CRS – are not well understood.12

CRS, an inflammatory response indicative of high immune activity, is the most frequently observed toxicity. Most patients who develop CRS experience mild or moderate flu-like symptoms that subside over time, but some experience severe CRS that can lead to life-threatening multi-organ dysfunction. Symptoms of CRS can appear weeks after infusion and require intensive care unit (ICU)–level care through the acute phase.

Neurotoxicity, also known by the technical term “CAR-T-cell-related encephalopathy syndrome,” is the second most common AE, and it can occur concurrent with or after CRS.

Tisagenlecleucel was approved with a boxed warning for CRS and neurologic events and, because of the observed risks, a Risk Evaluation and Mitigation Strategy.

Since the early days of CAR T-cell development, when the first cases of CRS threw physicians for a loop, investigators have developed algorithms and protocols to identify patients at greatest risk of AEs and to manage their occurrence. Research has shown, for instance, that if a patient has the cytokine marker interleukin (IL)-6, he or she is more likely to progress to severe CRS; in clinical trials of tisagenlecleucel, administration of the IL-6 receptor-blocking antibody tocilizumab led to complete resolution of CRS in 69 percent of patients. On the same day as tisagenlecleucel’s approval, the FDA expanded the indication for tocilizumab to include treatment of CAR T cell–induced, severe or life-threatening CRS in patients ≥2 years of age.1

Cerebral edema also remains poorly understood and difficult to manage.

Recently, investigators from multiple institutions and medical disciplines formed the CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group to develop a monitoring, grading, and management system for acute toxicities associated with these new therapies.12

Although the side effects are not trivial, experienced transplant centers are familiar with managing most of them, Dr. Majhail noted. His hope is that future generations of CAR T-cell products will offer better safety profiles, with clinical trials clarifying the optimal timing of CAR T-cell administration and the therapies to manage toxicities.

“We know the concept – that you can use engineered cells to do specific things in vivo for therapy – is correct,” Dr. Gee affirmed. “Now we just need to know more about for how long and in which patients.”

The Health Economics of CAR T-Cell Therapy

The unprecedented response rates with tisagenlecleucel come at unprecedentedly high costs: Novartis priced tisagenlecleucel at $475,000 for a single infusion. Despite the sticker shock experienced by most, some analysts consider it a reasonable list price for this new line of therapies.

“The price does make your eyes water at first glance, but this product is potentially transformative in the management of this patient population. I think it’s in the right ballpark,” said Stephen Palmer, PhD, professor and deputy director of the Team for Economic Evaluation and Health Technology Assessment at the Centre for Health Economics at the University of York in the United Kingdom. “However, inevitably, there is significant uncertainty regarding whether the modeled long-term value will be realized in clinical practice.”

CAR T-cell products are truly personalized, likely costing more to manufacture per individual patient than any other therapy, Dr. Palmer offered in defense of the price tag. Also, they address an unmet need and offer treatment that is potentially curative.

In support of their pricing, Novartis cited a health technology assessment (HTA) published in February 2017 by the U.K.’s National Institute for Health and Care Excellence (NICE), of which Dr. Palmer was a senior author.13 The NICE assessment determined that a cost-effective price for CAR-T therapy would range from $600,000 to $750,000. Based on that analysis, and the current cost of allogeneic hematopoietic cell transplantation (HCT), which Novartis says is between $540,000 and $800,000 for the first year, the company argues that their price is cost effective.

However, Dr. Price explained, it is not a simple “apples-to-apples” comparison. The NICE estimate was taken from an “exploratory analysis and based on hypothetical data, albeit designed to be as realistic as possible in terms of the outcomes we might expect to see with these technologies, according to results reported from early studies.”

Dr. Palmer and colleagues based their assumptions on the early, single-center, pilot data on tisagenlecleucel in the first 30 children and adults treated.14 That study showed a CR rate of 90 percent, which he noted is better than the 83 percent response rate currently quoted for tisagenlecleucel.

“The company set the price based on value assessments for initial indications, and it can’t necessarily be assumed to provide similar value in subsequent indications,” he added. “Inevitably, differences [in response] would have a marked impact on the cost-effectiveness estimates we generated.”

Thirty-Day Money-Back Guarantee

To mitigate concerns over the drug’s list price, Novartis entered a unique “outcomes-based” payment model with the U.S. Centers for Medicare and Medicaid Services (CMS). The system will not pay for tisagenlecleucel unless the pediatric or young adult patient with ALL who receives it responds to the treatment within 30 days of administration.

This model means that “there is a mechanism in place to ensure that value is more closely aligned to patient outcome,” Dr. Palmer explained. If the drug is approved for additional indications such as non-Hodgkin lymphoma (NHL), in which response rates have only reached 39 percent, “essentially, you will only pay for the 39 percent of patients with NHL who respond, rather than the 83 percent of patients with ALL who respond.”

“Innovations like this reinforce our belief that current health-care payment systems need to be modernized … to ensure access to new high-cost therapies, including therapies that have the potential to cure the sickest patients,” said CMS Administrator Seema Verma in a press release.15

“Generally, it is a positive development that companies are relating their pricing decisions to value assessments in the U.S.,” said Dr. Palmer, “ensuring that the price we pay is more closely linked to the value we think the product delivers to the patient and the efficiency of the health-care system.”

However, there are limitations to this innovative approach. Dr. Majhail noted that 30-day response might not be the optimal measure of efficacy, with most patients achieving remission at this timepoint with conventional therapies. “We may observe some tumor shrinkage at one month in certain patients, but this early response doesn’t always translate into a long-term response,” he explained. “The therapy may still stop working, and the cancer may come back.”

To further mitigate longer-term financial toxicity risk, Dr. Palmer envisions another innovative payment model. Similar to a leasing arrangement, the payer would remit an annual payment of, say, 25 percent of the purchase price every year for four years, with the payment contingent on survival each year. “This would further reduce the uncertainties about long-term efficacy and more closely align the payment to the actual value being achieved,” he said.

Even if proven cost-effective in terms of survival, the price tag does not account for the management of side effects of CAR T-cell therapy, including CRS and B-cell aplasia. Dr. Majhail considers the Novartis price a “bit misleading,” because it doesn’t include any of the attendant costs of administering CAR T-cell therapy or managing its associated complications.

“If the therapy doesn’t work, you may not have to pay that $475,000, but you do have to pay for everything else that’s going on,” said Dr. Majhail. This includes “the scans and tests needed to determine if the patient is a candidate for CAR T-cell therapy, staging the patient, performing lung function testing, collecting the cells by apheresis, processing cells in the lab, treating patients with firstline chemotherapy, and the in-patient hospital stay.” If and when AEs occur, that could expand to include a stay in the ICU and the administration of tocilizumab.

Dr. Majhail estimates the total bill will equal or exceed the costs associated with HCT. His worry is that while only a few hundred HCTs are performed each year, should CAR T-cell therapies live up to the hype and prove effective in more common cancers, the numbers may increase exponentially. “If we develop CAR-T cell therapies for a larger variety of diseases, at some point we may have to step back and ask, ‘How sustainable is this?’”—By Debra L. Beck

References

  1. U.S. Food and Drug Administration news release, August 20, 2017. Accessed September 29, 2017, from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm.
  2. U.S. Food and Drug Administration. “Transcript for the July 12, 2017, meeting of the Oncologic Drugs Advisory Committee (ODAC) (PM Session).” Accessed September 29, 2017, from https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM573721.pdf.
  3. American Society of Hematology press release, August 30, 2017. Accessed September 29, 2017, from http://www.hematology.org/Newsroom/Press-Releases/2017/7704.aspx.
  4. U.S. Food and Drug Administration news release, October 18, 2017. Accessed October 18, 2017, from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm581216.htm.
  5. American Cancer Society. “Survival rates for childhood leukemias.” Accessed September 29, 2017, from https://www.cancer.org/cancer/leukemia-in-children/detection-diagnosis-staging/survival-rates.html.
  6. Buechner J, Grupp SA, Maude SL, et al. Global registration trial of efficacy and safety of CTL019 in pediatric and young adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL): update to the interim analysis. Abstract #S476. Presented at the 22nd Congress of the European Hematology Association, June 24, 2017; Madrid, Spain.
  7. Schuster SJ, Bishop MR, Waller EK, et al. Global pivotal phase 2 trial of the CD19-targeted therapy CTL019 in adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL)—an interim analysis. Abstract #007. Presented at the 14th International Conference on Malignant Lymphoma, June 14, 2017; Lugano, Switzerland.
  8. Maus MV, Nikiforow S. The why, what, and how of the new FACT standards for immune effector cells. J Immunother Cancer. 2017;5:36.
  9. Novartis press release, August 30, 2017. Accessed September 28, 2017, from https://www.novartis.com/news/media-releases/novartis-receives-first-ever-fda-approval-car-t-cell-therapy-kymriahtm-ctl019.
  10. Bersenev A. “Failure in CAR T-cell products manufacturing.” Accessed October 3, 2017, from http://stemcellassays.com/2016/03/failures-cart-manufacturing/.
  11. Cellectis press release, September 4, 2017. Accessed October 2, 2017, from http://www.cellectis.com/en/press/cellectis-reports-clinical-hold-of-ucart123-studies.
  12. Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor T-cell therapy–assessment and management of toxicities. Nat Rev Clin Oncol. 2017 September 19. [Epub ahead of print]
  13. Hettle R, Corbett M, Hinde S, et al. The assessment and appraisal of regenerative medicine and cell therapy products: an exploration of methods for review, economic evaluation and appraisal. Health Technol Assess. 2017;21:1-204.
  14. Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507-17.
  15. CMS. “CMS: Innovative treatments call for innovative payment models and arrangements.” Accessed October 1, 2017, from https://www.cms.gov/Newsroom/MediaReleaseDatabase/Press-releases/2017-Press-releases-items/2017-08-30-2.html.

After gaining U.S. Food and Drug Administration (FDA) approval for tisagenlecleucel, Novartis has become the “leader of the pack” in the field of gene therapy, but several other pharmaceutical manufacturers are drafting on Novartis’s success. On October 18, 2017, Kite Pharma, became the lead CAR T-cell manufacturer, at least from the perspective of patient impact.1

The company received FDA approval for axicabtagene ciloleucel (axi-cel, formerly known as KTE-C19) to treat patients with three subtypes of aggressive non-Hodgkin lymphoma (NHL), relapsed or refractory diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma, and primary mediastinal B-cell lymphoma in patients who are ineligible for autologous hematopoietic cell transplantation. This marks the first approval in adults and affects a patient population that is approximately more than quadruple the size of tisagenlecleucel’s. Kite Pharma has also submitted for approval in Europe and expects a decision and potential launch there in early 2018.

The axi-cel approval was based on data from the ZUMA-1 trial, which enrolled 111 patients from 22 institutions, 101 of whom (91%) received axi-cel.2 The trial met its primary endpoint with an objective response rate (ORR) of 82 percent after a single infusion. At a median follow-up of 8.7 months, 44 percent of patients showed continued response, including 39 percent who were in complete remission.

Kite Pharma is planning for a “controlled” launch of axi-cel at 20 sites, with plans to extend to 72 academic centers within a year of FDA approval. The company is already working to secure reimbursement agreements with payers so that sites can begin prescribing axi-cel “within days” of approval.

There are approximately 40 additional companies, many in partnership with academic institutions, actively developing chimeric antigen receptor (CAR) T-cell therapies for a diverse set of indications, though some of the efforts have been sidelined by safety concerns.

Juno Therapeutics was an early leader in the CAR T-cell race with JCAR015 for patients with acute lymphocytic leukemia (ALL), but lost ground when a series of toxicity-related setbacks culminated in the decision to halt the JCAR015 development program. The company then pivoted to focus on the rest of its deep CAR T-cell pipeline, like JCAR017. Data from the phase I TRANSCEND study presented earlier this year showed an ORR of 86 percent and a complete response rate of 59 percent in patients with relapsed or refractory DLBCL treated with JCAR017.3

Juno Therapeutics has 11 ongoing CAR T-cell trials, covering a range of indications from NHL, pediatric ALL, multiple myeloma, acute myeloid leukemia (AML), non-small cell lung cancer/mesothelioma, pediatric neuroblastoma, ovarian cancer, breast cancer, and lung cancer. All candidates are in phase I trials, except two that are in phase I/II trials.4

The CAR T-cell products furthest along in development target the CD19 antigen, but companies are exploring alternate targets. For instance, Juno Therapeutics’ pipeline includes agents that target:

  • CD22 in NHL and pediatric ALL
  • WT1, an intracellular protein that is overexpressed in a number of
    cancers, including AML and non-small cell lung, breast, pancreatic,
    ovarian, and colorectal cancers
  • MUC16, a protein overexpressed in most ovarian cancers
  • B-cell maturation antigen, which is expressed on all plasma cells,
    including cancerous plasma cells in myeloma

References

  1. U.S. Food and Drug Administration news release, August 20, 2017. Accessed September 29, 2017, from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm.
  2. Locke FL, Neelapu SS, Bartlett NL, et al. Clinical and biologic covariates of outcomes in ZUMA-1: a pivotal trial of axicabtagene ciloleucel (axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (r-NHL). Abstract #7512. Presented at the 2017 ASCO Annual Meeting, June 5, 2017; Chicago, IL.
  3. Abramson JS, Palomba ML, Gordon LI, et al. High CR rates in relapsed/refractory (R/R) aggressive B-NHL treated with the CD19-directed CAR T cell product JCAR017 (TRANSCEND NHL 001). Abstract 128. Presented at the 14th International Conference on Malignant Lymphoma, June 17, 2017; Lugano, Switzerland.
  4. Juno Therapeutics. “Developing best-in-class therapies.” Accessed October 3, 2017, from https://www.junotherapeutics.com/our-pipeline/.

Hematologists have been on the front lines of cancer immunotherapy, including the development of chimeric antigen receptor (CAR) T-cell therapy and immune checkpoint inhibitors. In support of this promising area of hematology, the American Society of Hematology (ASH) highlighted immunologic treatments for hematologic malignancies as one of its six research priorities in its Agenda for Hematology Research. The Society also has assembled a Task Force on Immunotherapy to address key issues pertaining to this area of precision medicine. In addition, ASH has designated immunotherapy a focus of upcoming meetings, with the goal of improving these therapies and speeding their progress from bench to bedside.

Here are a few areas in which ASH is focusing on the importance of Immunotherapy throughout the year.


The ASH Agenda for Hematology Research: The ASH Agenda for Hematology Research serves as a roadmap for the prioritization of research support across the hematology community, including recommendations for dedicated resources from funding agencies and foundations.

One of ASH’s priorities is: Immunologic Treatments of Hematologic Malignancies: Moving Beyond Salvage Therapy to Curative Eradication of Minimal Residual Disease

Next-generation clinical studies will address important questions about emerging immunologic therapies but require an improved understanding of the basic biology of the immune system, including adaptive immunity, innate immunity, adjuvants, and tumor immune-surveillance.

To tackle these questions, critical near-term research priorities should include:

  • Optimizing the use of CAR T-cell and checkpoint blockade strategies to cure hematologic malignancies and eradicate minimal residual disease
  • Improving efficacy and reducing toxicity for CAR T-cell and checkpoint blockade strategies
  • Improving effectiveness of existing curative therapies, specifically allogeneic hematopoietic cell transplantation

For more information about ASH’s research priorities in this area, visit hematology.org/research/agenda.


Introducing the ASH Summit on Emerging Immunotherapies for Hematologic Diseases: ASH’s newest meeting will examine preclinical and clinical factors influencing the effective development, regulation, and implementation of immunotherapies for hematologic diseases. The summit’s interactive format will encourage collaboration among clinicians, academicians, industry, regulators, patient advocates, and other experts focused on or interested in immunotherapy research.

Attendees will:

  1. Discuss the current state of the science for cellular therapies, checkpoint inhibitors, and other forms of immunotherapy as it relates to all hematologic diseases
  2. Identify knowledge gaps and challenges that need to be addressed to improve the use of immunotherapies
  3. Outline strategies needed to improve effective regulation and implementation of these therapies into clinical practice

Summit Co-Chairs:

  • Catherine Bollard, MD, Children’s National Health System, Washington, DC
  • Rodrigo Calado, MD, PhD, University of São Paulo, Brazil
  • Sergio Giralt, MD, Memorial Sloan Kettering Cancer Center, New York, NY
  • Jeffrey Miller, MD, University of Minnesota, Minneapolis, MN

For more information on the summit, visit hematology.org/Immunotherapies. For more information on the Task Force on Immunotherapies, please contact Alice Kuaban at akuaban@hematology.org.


Immunotherapy at the Annual Meeting: Several sessions at the 2017 ASH Annual Meeting will focus on the development of immunotherapies for hematologic malignancies, appropriate patient selection, management of toxicities, and the practical considerations for using immunotherapies in clinical practice. To view details on all 2017 ASH Annual Meeting sessions focused on immunotherapies, visit hematology.org/annual-meeting/program.

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