Cellular Therapy

A new federal oversight structure aims to smooth and speed the development of gene therapies, according to Francis S. Collins, MD, director of the National Institutes of Health, and Scott Gottlieb, MD, Food and Drug Administration commissioner.

“As the NIH, the FDA, and research entities have moved to strengthen their individual oversight efforts, some overlaps have occurred,” Dr. Collins and Dr. Gottlieb wrote Aug. 15 in the New England Journal of Medicine. “Substantial duplication has arisen in the submission of initial protocols, annual reports, amendments, and reports of serious adverse events. Originally, these overlaps – which affect no other field in biomedical research – were viewed as harmonized reporting that enabled FDA to conduct regulatory oversight while maintaining confidentiality with sponsors and allowed NIH to provide transparency with regard to the research.”

With three approved treatments – two CAR T therapies and a treatment for a genetic retinal dystrophy – and more than 700 active investigational new drug applications in front of the FDA, “it seems reasonable to envision a day when gene therapy will be a mainstay of treatment for many diseases,” according to the editorial.

To remedy the situation, NIH officials Aug. 16 posted a proposed update to NIH guidance that seeks “to reduce the duplicative oversight burden by further limiting the role of NIH and RAC [Recombinant DNA Advisory Committee] in assessing gene therapy protocols and reviewing their safety information,” Dr. Collins and Dr. Gottlieb wrote. “Specifically, these proposals will eliminate RAC review and reporting requirements to the NIH for human gene therapy protocols. They will also revise the responsibility of institutional Biosafety Committees, which have local oversight for this research, making their review of human gene therapy protocols consistent with review of other research subject to the NIH Guidelines. Such streamlining will also appropriately place the focus of the NIH Guidelines squarely back on laboratory biosafety.”

RAC was originally established in 1974 to advise the NIH director on research involving manipulation of nucleic acids, but was later expanded to review and discuss protocols for gene therapy in humans.

The proposed structure provides an opportunity “to return the RAC to the spirit in which it was founded. ... The NIH envisions using the RAC as an advisory board on today’s emerging technologies, such as gene editing, synthetic biology, and neurotechnology, while harnessing the attributes that have long ensured its transparency,” they wrote.

This latest proposal follows a suite of FDA draft guidances on gene therapies issued in July that proposed new guidance on manufacturing issues, long-term follow-up, and pathways for clinical development in certain areas.

The guidance is scheduled for publication in the Federal Register on Aug. 17.

[email protected]

SOURCE: Collins FS and Gottlieb S. N Engl J Med. doi: 10.1056/NEJMp1810628.

A new federal oversight structure aims to smooth and speed the development of gene therapies, according to Francis S. Collins, MD, director of the National Institutes of Health, and Scott Gottlieb, MD, Food and Drug Administration commissioner.

“As the NIH, the FDA, and research entities have moved to strengthen their individual oversight efforts, some overlaps have occurred,” Dr. Collins and Dr. Gottlieb wrote Aug. 15 in the New England Journal of Medicine. “Substantial duplication has arisen in the submission of initial protocols, annual reports, amendments, and reports of serious adverse events. Originally, these overlaps – which affect no other field in biomedical research – were viewed as harmonized reporting that enabled FDA to conduct regulatory oversight while maintaining confidentiality with sponsors and allowed NIH to provide transparency with regard to the research.”

With three approved treatments – two CAR T therapies and a treatment for a genetic retinal dystrophy – and more than 700 active investigational new drug applications in front of the FDA, “it seems reasonable to envision a day when gene therapy will be a mainstay of treatment for many diseases,” according to the editorial.

To remedy the situation, NIH officials Aug. 16 posted a proposed update to NIH guidance that seeks “to reduce the duplicative oversight burden by further limiting the role of NIH and RAC [Recombinant DNA Advisory Committee] in assessing gene therapy protocols and reviewing their safety information,” Dr. Collins and Dr. Gottlieb wrote. “Specifically, these proposals will eliminate RAC review and reporting requirements to the NIH for human gene therapy protocols. They will also revise the responsibility of institutional Biosafety Committees, which have local oversight for this research, making their review of human gene therapy protocols consistent with review of other research subject to the NIH Guidelines. Such streamlining will also appropriately place the focus of the NIH Guidelines squarely back on laboratory biosafety.”

RAC was originally established in 1974 to advise the NIH director on research involving manipulation of nucleic acids, but was later expanded to review and discuss protocols for gene therapy in humans.

The proposed structure provides an opportunity “to return the RAC to the spirit in which it was founded. ... The NIH envisions using the RAC as an advisory board on today’s emerging technologies, such as gene editing, synthetic biology, and neurotechnology, while harnessing the attributes that have long ensured its transparency,” they wrote.

This latest proposal follows a suite of FDA draft guidances on gene therapies issued in July that proposed new guidance on manufacturing issues, long-term follow-up, and pathways for clinical development in certain areas.

The guidance is scheduled for publication in the Federal Register on Aug. 17.

[email protected]

SOURCE: Collins FS and Gottlieb S. N Engl J Med. doi: 10.1056/NEJMp1810628.

A new federal oversight structure aims to smooth and speed the development of gene therapies, according to Francis S. Collins, MD, director of the National Institutes of Health, and Scott Gottlieb, MD, Food and Drug Administration commissioner.

“As the NIH, the FDA, and research entities have moved to strengthen their individual oversight efforts, some overlaps have occurred,” Dr. Collins and Dr. Gottlieb wrote Aug. 15 in the New England Journal of Medicine. “Substantial duplication has arisen in the submission of initial protocols, annual reports, amendments, and reports of serious adverse events. Originally, these overlaps – which affect no other field in biomedical research – were viewed as harmonized reporting that enabled FDA to conduct regulatory oversight while maintaining confidentiality with sponsors and allowed NIH to provide transparency with regard to the research.”

With three approved treatments – two CAR T therapies and a treatment for a genetic retinal dystrophy – and more than 700 active investigational new drug applications in front of the FDA, “it seems reasonable to envision a day when gene therapy will be a mainstay of treatment for many diseases,” according to the editorial.

To remedy the situation, NIH officials Aug. 16 posted a proposed update to NIH guidance that seeks “to reduce the duplicative oversight burden by further limiting the role of NIH and RAC [Recombinant DNA Advisory Committee] in assessing gene therapy protocols and reviewing their safety information,” Dr. Collins and Dr. Gottlieb wrote. “Specifically, these proposals will eliminate RAC review and reporting requirements to the NIH for human gene therapy protocols. They will also revise the responsibility of institutional Biosafety Committees, which have local oversight for this research, making their review of human gene therapy protocols consistent with review of other research subject to the NIH Guidelines. Such streamlining will also appropriately place the focus of the NIH Guidelines squarely back on laboratory biosafety.”

RAC was originally established in 1974 to advise the NIH director on research involving manipulation of nucleic acids, but was later expanded to review and discuss protocols for gene therapy in humans.

The proposed structure provides an opportunity “to return the RAC to the spirit in which it was founded. ... The NIH envisions using the RAC as an advisory board on today’s emerging technologies, such as gene editing, synthetic biology, and neurotechnology, while harnessing the attributes that have long ensured its transparency,” they wrote.

This latest proposal follows a suite of FDA draft guidances on gene therapies issued in July that proposed new guidance on manufacturing issues, long-term follow-up, and pathways for clinical development in certain areas.

The guidance is scheduled for publication in the Federal Register on Aug. 17.

[email protected]

SOURCE: Collins FS and Gottlieb S. N Engl J Med. doi: 10.1056/NEJMp1810628.

Release Date: July 15, 2018
Expiration Date: July 14, 2019

Note: This activity is no longer available for credit

Introductory Comments: (Duration: 9 minutes)

Aaron P. Rapoport, MD
Bone Marrow Transplant Program
University of Maryland School of Medicine
Baltimore, MD

Presentation: (Duration: 39 minutes)

Carl H. June, MD
Richard W. Vague Professor in Immunotherapy
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA

Provided by:

Learning Objectives

• Review clinical data and individual case studies to determine where CAR T-cell therapy might be appropriate in the treatment of adult and pediatric patients with leukemia, lymphoma, and multiple myeloma.

• Discuss the management of cytotoxicity of CAR T-cell therapy.

Target Audience

Hematologists, oncologists, and other members of the healthcare team who treat or manage patients with hematologic malignancies.

Statement of Need

It is critical that clinicians managing patients with acute leukemia and other hematologic malignancies are cognizant of exciting breakthroughs and are also able to integrate recent progress into practice. However, given the overwhelming influx of data, it is no surprise that many hematology professionals face difficulties in identifying the most relevant findings for clinical practice. Hematologists are unable to stay abreast of the latest evidence on investigational agents. Educational programs are thus crucial to address this important professional practice gap.

Faculty

Carl H. June, MD
Richard W. Vague Professor in Immunotherapy
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA
Disclosures: Consultant: Novartis; Grant/Research support and royalties/IPR: Novartis
Stockholder: Tmunity Therapeutics, Inc.

Aaron P. Rapoport, MD
Bone Marrow Transplant Program
University of Maryland School of Medicine
Baltimore, Maryland
Disclosures: No relevant financial relationships with a commercial supporter

Permissions

• Slide 3: Complex tumor, host and environmental factors govern the strength and timing of anti-cancer immune responses
  • Reprinted from Immunity, Vol 39/No 1, Chen DS, Mellman I, Oncology meets immunology: the cancer-immunity cycle, pp 1-10, 2013, with permission from Elsevier
• Slide 9: Genes differentially expressed in CART19 cellular infusion products from CLL patients
  • From Fraietta JA, Lacey SF, Orlando EJ, . . . June CH, Melenhorst JJ. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med 2018; 24:563-571
• Slide 10: Characterization of CLL CAR T cells in NSG CLL model
  • Same as slide 9
• Slide 15: First adult ALL patient
  • Photos originally published in Kaiser Health News/Photo courtesy of Dr Keith Eaton. Available at: https://khn.org/news/cascade-of-costs-could-push-new-gene-therapy-above-1-million-per-patient/
• Slide 21: Efficient trafficking of CTL019 T Cells to CNS in ALL
  • From N Engl J Med, Grupp SA, Kalos M, Barrett D, . . V. June CH, Chimeric antigen receptor-modified T cells for acute lymphoid leukemia, Volume No 368, pp 1509-1518. Copyright © 2013 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
• Slide 26: Long-term persistence and expression of CTL019 is associated with durable remission in leukemia: Predictive Biomarker
  • From Porter DL, Hwang WT, Frey NV . . . June CH. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 2015; 7(303):303ra139. Reprinted with permission from AAAS.
• Slide 28: Rapid massive expansion of clonal CART cell population in patient #10
  • Initially published in Fraietta JA, Nobles CL, Sammons MA, . . . June CH, Melenhors JJ. Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells. Nature 2018; 558(7709):307-312
• Slide 29: Mapping CAR integration site in Pt #10
  • Same as slide 28.
• Slide 31: Long-term stable persistence of TET2-deficient CAR T cells in Pt #10
  • Same as slide 28
• Slide 32: Epigenetic and genetic changes uncovered by ATAC-seq in Pt #10
  • Same as slide 28.
• Slide 33: TET2 knock down in healthy donor T cells
  • Same as slide 28.
• Slide 34: TET2 knock down in healthy donor T cells
  • Same as slide 28.
• Slide 36: CAR T for myeloma: BCMA
  • From Rickert RC, Jellusova J, Miletic AV. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev 2011; 244(1):115-33. Reprinted with permission from John Wiley and Sons.
• Slide 38: CAR T for myeloma: Patient #1
  • Photo originally published by UT Southwestern Medical Center. Available at: https://www.utsouthwestern.edu/newsroom/articles/year-2018/wright-car-t.html
• Slide 39: Autoimmunity is the “Achilles’ Heel” of immunotherapy
  • First published in June CH, Warshauer JT, and Bluestone JA. Is autoimmunity the Achilles’ heel of cancer immunotherapy? Nat Med 2017;23(5):540-7
• Slide 41: Multiplex CRISPR /Cas9 editing: Universal T cells TCR, HLA, PD-1, CTLA-4 and Fas
  • From Ren J, Zhang X, Liu X, Fang C, Jiang S, June CH, Zhao Y. A versatile system for rapid multiplex genome-edited CAR T cell generation. Oncotarget 2017; 8:17002-17011.
• Slide 45: CAR T-cell trials for cancer are now global
  • From June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science 2018; 359:1361-1365. Reprinted with permission from AAAS.

Disclaimer

The content and views presented in this educational activity are those of the author and do not necessarily reflect those of Hemedicus or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.

Release Date: July 15, 2018
Expiration Date: July 14, 2019

Note: This activity is no longer available for credit

Introductory Comments: (Duration: 9 minutes)

Aaron P. Rapoport, MD
Bone Marrow Transplant Program
University of Maryland School of Medicine
Baltimore, MD

Presentation: (Duration: 39 minutes)

Carl H. June, MD
Richard W. Vague Professor in Immunotherapy
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA

Provided by:

Learning Objectives

• Review clinical data and individual case studies to determine where CAR T-cell therapy might be appropriate in the treatment of adult and pediatric patients with leukemia, lymphoma, and multiple myeloma.

• Discuss the management of cytotoxicity of CAR T-cell therapy.

Target Audience

Hematologists, oncologists, and other members of the healthcare team who treat or manage patients with hematologic malignancies.

Statement of Need

It is critical that clinicians managing patients with acute leukemia and other hematologic malignancies are cognizant of exciting breakthroughs and are also able to integrate recent progress into practice. However, given the overwhelming influx of data, it is no surprise that many hematology professionals face difficulties in identifying the most relevant findings for clinical practice. Hematologists are unable to stay abreast of the latest evidence on investigational agents. Educational programs are thus crucial to address this important professional practice gap.

Faculty

Carl H. June, MD
Richard W. Vague Professor in Immunotherapy
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA
Disclosures: Consultant: Novartis; Grant/Research support and royalties/IPR: Novartis
Stockholder: Tmunity Therapeutics, Inc.

Aaron P. Rapoport, MD
Bone Marrow Transplant Program
University of Maryland School of Medicine
Baltimore, Maryland
Disclosures: No relevant financial relationships with a commercial supporter

Permissions

• Slide 3: Complex tumor, host and environmental factors govern the strength and timing of anti-cancer immune responses
  • Reprinted from Immunity, Vol 39/No 1, Chen DS, Mellman I, Oncology meets immunology: the cancer-immunity cycle, pp 1-10, 2013, with permission from Elsevier
• Slide 9: Genes differentially expressed in CART19 cellular infusion products from CLL patients
  • From Fraietta JA, Lacey SF, Orlando EJ, . . . June CH, Melenhorst JJ. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med 2018; 24:563-571
• Slide 10: Characterization of CLL CAR T cells in NSG CLL model
  • Same as slide 9
• Slide 15: First adult ALL patient
  • Photos originally published in Kaiser Health News/Photo courtesy of Dr Keith Eaton. Available at: https://khn.org/news/cascade-of-costs-could-push-new-gene-therapy-above-1-million-per-patient/
• Slide 21: Efficient trafficking of CTL019 T Cells to CNS in ALL
  • From N Engl J Med, Grupp SA, Kalos M, Barrett D, . . V. June CH, Chimeric antigen receptor-modified T cells for acute lymphoid leukemia, Volume No 368, pp 1509-1518. Copyright © 2013 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
• Slide 26: Long-term persistence and expression of CTL019 is associated with durable remission in leukemia: Predictive Biomarker
  • From Porter DL, Hwang WT, Frey NV . . . June CH. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 2015; 7(303):303ra139. Reprinted with permission from AAAS.
• Slide 28: Rapid massive expansion of clonal CART cell population in patient #10
  • Initially published in Fraietta JA, Nobles CL, Sammons MA, . . . June CH, Melenhors JJ. Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells. Nature 2018; 558(7709):307-312
• Slide 29: Mapping CAR integration site in Pt #10
  • Same as slide 28.
• Slide 31: Long-term stable persistence of TET2-deficient CAR T cells in Pt #10
  • Same as slide 28
• Slide 32: Epigenetic and genetic changes uncovered by ATAC-seq in Pt #10
  • Same as slide 28.
• Slide 33: TET2 knock down in healthy donor T cells
  • Same as slide 28.
• Slide 34: TET2 knock down in healthy donor T cells
  • Same as slide 28.
• Slide 36: CAR T for myeloma: BCMA
  • From Rickert RC, Jellusova J, Miletic AV. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev 2011; 244(1):115-33. Reprinted with permission from John Wiley and Sons.
• Slide 38: CAR T for myeloma: Patient #1
  • Photo originally published by UT Southwestern Medical Center. Available at: https://www.utsouthwestern.edu/newsroom/articles/year-2018/wright-car-t.html
• Slide 39: Autoimmunity is the “Achilles’ Heel” of immunotherapy
  • First published in June CH, Warshauer JT, and Bluestone JA. Is autoimmunity the Achilles’ heel of cancer immunotherapy? Nat Med 2017;23(5):540-7
• Slide 41: Multiplex CRISPR /Cas9 editing: Universal T cells TCR, HLA, PD-1, CTLA-4 and Fas
  • From Ren J, Zhang X, Liu X, Fang C, Jiang S, June CH, Zhao Y. A versatile system for rapid multiplex genome-edited CAR T cell generation. Oncotarget 2017; 8:17002-17011.
• Slide 45: CAR T-cell trials for cancer are now global
  • From June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science 2018; 359:1361-1365. Reprinted with permission from AAAS.

Disclaimer

The content and views presented in this educational activity are those of the author and do not necessarily reflect those of Hemedicus or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.

Release Date: July 15, 2018
Expiration Date: July 14, 2019

Note: This activity is no longer available for credit

Introductory Comments: (Duration: 9 minutes)

Aaron P. Rapoport, MD
Bone Marrow Transplant Program
University of Maryland School of Medicine
Baltimore, MD

Presentation: (Duration: 39 minutes)

Carl H. June, MD
Richard W. Vague Professor in Immunotherapy
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA

Provided by:

Learning Objectives

• Review clinical data and individual case studies to determine where CAR T-cell therapy might be appropriate in the treatment of adult and pediatric patients with leukemia, lymphoma, and multiple myeloma.

• Discuss the management of cytotoxicity of CAR T-cell therapy.

Target Audience

Hematologists, oncologists, and other members of the healthcare team who treat or manage patients with hematologic malignancies.

Statement of Need

It is critical that clinicians managing patients with acute leukemia and other hematologic malignancies are cognizant of exciting breakthroughs and are also able to integrate recent progress into practice. However, given the overwhelming influx of data, it is no surprise that many hematology professionals face difficulties in identifying the most relevant findings for clinical practice. Hematologists are unable to stay abreast of the latest evidence on investigational agents. Educational programs are thus crucial to address this important professional practice gap.

Faculty

Carl H. June, MD
Richard W. Vague Professor in Immunotherapy
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA
Disclosures: Consultant: Novartis; Grant/Research support and royalties/IPR: Novartis
Stockholder: Tmunity Therapeutics, Inc.

Aaron P. Rapoport, MD
Bone Marrow Transplant Program
University of Maryland School of Medicine
Baltimore, Maryland
Disclosures: No relevant financial relationships with a commercial supporter

Permissions

• Slide 3: Complex tumor, host and environmental factors govern the strength and timing of anti-cancer immune responses
  • Reprinted from Immunity, Vol 39/No 1, Chen DS, Mellman I, Oncology meets immunology: the cancer-immunity cycle, pp 1-10, 2013, with permission from Elsevier
• Slide 9: Genes differentially expressed in CART19 cellular infusion products from CLL patients
  • From Fraietta JA, Lacey SF, Orlando EJ, . . . June CH, Melenhorst JJ. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med 2018; 24:563-571
• Slide 10: Characterization of CLL CAR T cells in NSG CLL model
  • Same as slide 9
• Slide 15: First adult ALL patient
  • Photos originally published in Kaiser Health News/Photo courtesy of Dr Keith Eaton. Available at: https://khn.org/news/cascade-of-costs-could-push-new-gene-therapy-above-1-million-per-patient/
• Slide 21: Efficient trafficking of CTL019 T Cells to CNS in ALL
  • From N Engl J Med, Grupp SA, Kalos M, Barrett D, . . V. June CH, Chimeric antigen receptor-modified T cells for acute lymphoid leukemia, Volume No 368, pp 1509-1518. Copyright © 2013 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
• Slide 26: Long-term persistence and expression of CTL019 is associated with durable remission in leukemia: Predictive Biomarker
  • From Porter DL, Hwang WT, Frey NV . . . June CH. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 2015; 7(303):303ra139. Reprinted with permission from AAAS.
• Slide 28: Rapid massive expansion of clonal CART cell population in patient #10
  • Initially published in Fraietta JA, Nobles CL, Sammons MA, . . . June CH, Melenhors JJ. Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells. Nature 2018; 558(7709):307-312
• Slide 29: Mapping CAR integration site in Pt #10
  • Same as slide 28.
• Slide 31: Long-term stable persistence of TET2-deficient CAR T cells in Pt #10
  • Same as slide 28
• Slide 32: Epigenetic and genetic changes uncovered by ATAC-seq in Pt #10
  • Same as slide 28.
• Slide 33: TET2 knock down in healthy donor T cells
  • Same as slide 28.
• Slide 34: TET2 knock down in healthy donor T cells
  • Same as slide 28.
• Slide 36: CAR T for myeloma: BCMA
  • From Rickert RC, Jellusova J, Miletic AV. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev 2011; 244(1):115-33. Reprinted with permission from John Wiley and Sons.
• Slide 38: CAR T for myeloma: Patient #1
  • Photo originally published by UT Southwestern Medical Center. Available at: https://www.utsouthwestern.edu/newsroom/articles/year-2018/wright-car-t.html
• Slide 39: Autoimmunity is the “Achilles’ Heel” of immunotherapy
  • First published in June CH, Warshauer JT, and Bluestone JA. Is autoimmunity the Achilles’ heel of cancer immunotherapy? Nat Med 2017;23(5):540-7
• Slide 41: Multiplex CRISPR /Cas9 editing: Universal T cells TCR, HLA, PD-1, CTLA-4 and Fas
  • From Ren J, Zhang X, Liu X, Fang C, Jiang S, June CH, Zhao Y. A versatile system for rapid multiplex genome-edited CAR T cell generation. Oncotarget 2017; 8:17002-17011.
• Slide 45: CAR T-cell trials for cancer are now global
  • From June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science 2018; 359:1361-1365. Reprinted with permission from AAAS.

Disclaimer

The content and views presented in this educational activity are those of the author and do not necessarily reflect those of Hemedicus or Frontline Medical Communications. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.

Physicians may finally have some clarity on payment for inpatient administration of two chimeric antigen receptor–T-cell therapies if a proposed rule from the Centers of Medicare & Medicaid Services becomes final.

The agency is seeking to assign ICD-10-PCS codes XW033C3 and XW043C3 to the use of axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) in the inpatient setting for fiscal year 2019. The agency is also considering the creation of a new Medicare Severity–Diagnosis Related Group (MS-DRG) code for procedures involving the use of chimeric antigen receptor (CAR) T-cell therapy drugs. The proposal was published in May in the Federal Register.

The proposal demonstrates that CMS is listening to physicians’ concerns about CAR T payments and working to provide a more reasonable framework, said Stephanie Farnia, director of health policy and strategic relations for the American Society for Blood and Marrow Transplantation.

“The primary point of significance is that CAR-T care episodes should be assigned to a specific MS-DRG in FY2019, which will give physicians a clearer sense of inpatient reimbursement in advance,” she said in an interview.

Uncertainty about inpatient payment for administration of the two approved CAR-T therapies have been a lingering concern of specialists using, or interested in using, the therapies. In April 2018, CMS announced payment rates for outpatient administration of the two drugs, settling on $395,380 for axicabtagene ciloleucel and $500,839 for tisagenlecleucel. The two medications have list prices of $373,000 and $475,000, respectively.

However, physicians noted that even if the drugs are first administered in the outpatient setting, inpatient care is likely to occur with CAR T-cell therapies because some patients will need to be admitted in order to be monitored for serious side effects. In such cases, all payments will become part of the inpatient stay per CMS’ 3-day payment window rule.

In outlining the most recent payment proposal, CMS stated that its clinical advisers believe that patients receiving treatment with CAR T-cell therapy would have similar clinical characteristics and comorbidities as patients treated with autologous bone marrow transplant therapy, who are currently assigned to MS-DRG 016 “Autologous Bone Marrow Transplant with CC/MCC”. Therefore, CMS officials said they are suggesting ICD-10-PCS procedure codes XW033C3 and XW043C3 to pre-MDC MS-DRG 016. Additionally, the agency is proposing to revise the title of MS-DRG 016 from “Autologous Bone Marrow Transplant with CC/MCC” to “Autologous Bone Marrow Transplant with CC/MCC or T-cell Immunotherapy.”

However, the agency emphasized that it invites public comment on alternative payment approaches for CAR T-cell therapies in the context of the pending, new technology add-on payment applications by the CAR-T drugmakers Novartis Pharmaceuticals and Kite Pharma. If approved in the final rule, the technology add-on payments would provide an additional and separate payment equivalent to up to 50% of the product cost plus the MS-DRG payment received for the episode of care.

Other items in the proposed rule include approximate base payments for hematopoietic stem cell transplantation for fiscal 2019, which starts Oct. 1, 2018. The approximate per unit payment is $5,498, which translates to a total base payment of $64,790 for allogeneic bone marrow transplant (MS-DRG 014) for instance. In an American Society for Blood and Marrow Transplantation blog, Ms. Farnia outlined the approximate base weights and estimated reimbursements calculated from the rule.

CMS did not make any changes to the payment model for allogeneic hematopoietic cell transplantation despite continued requests by physicians for donor acquisition charges. Ms. Farnia encourages doctors to express to CMS the importance of such reimbursement during the comment period.

Public comments on the inpatient payment proposal are due by June 25, 2018, and can be submitted at https://www.regulations.gov. Additionally, CMS will convene a meeting of the Medicare Evidence Development & Coverage Advisory Committee on August 22, 2018, to consider whether to issue a national coverage policy for CAR T-cell therapies that would set consistent parameters for patient access.

Physicians may finally have some clarity on payment for inpatient administration of two chimeric antigen receptor–T-cell therapies if a proposed rule from the Centers of Medicare & Medicaid Services becomes final.

The agency is seeking to assign ICD-10-PCS codes XW033C3 and XW043C3 to the use of axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) in the inpatient setting for fiscal year 2019. The agency is also considering the creation of a new Medicare Severity–Diagnosis Related Group (MS-DRG) code for procedures involving the use of chimeric antigen receptor (CAR) T-cell therapy drugs. The proposal was published in May in the Federal Register.

The proposal demonstrates that CMS is listening to physicians’ concerns about CAR T payments and working to provide a more reasonable framework, said Stephanie Farnia, director of health policy and strategic relations for the American Society for Blood and Marrow Transplantation.

“The primary point of significance is that CAR-T care episodes should be assigned to a specific MS-DRG in FY2019, which will give physicians a clearer sense of inpatient reimbursement in advance,” she said in an interview.

Uncertainty about inpatient payment for administration of the two approved CAR-T therapies have been a lingering concern of specialists using, or interested in using, the therapies. In April 2018, CMS announced payment rates for outpatient administration of the two drugs, settling on $395,380 for axicabtagene ciloleucel and $500,839 for tisagenlecleucel. The two medications have list prices of $373,000 and $475,000, respectively.

However, physicians noted that even if the drugs are first administered in the outpatient setting, inpatient care is likely to occur with CAR T-cell therapies because some patients will need to be admitted in order to be monitored for serious side effects. In such cases, all payments will become part of the inpatient stay per CMS’ 3-day payment window rule.

In outlining the most recent payment proposal, CMS stated that its clinical advisers believe that patients receiving treatment with CAR T-cell therapy would have similar clinical characteristics and comorbidities as patients treated with autologous bone marrow transplant therapy, who are currently assigned to MS-DRG 016 “Autologous Bone Marrow Transplant with CC/MCC”. Therefore, CMS officials said they are suggesting ICD-10-PCS procedure codes XW033C3 and XW043C3 to pre-MDC MS-DRG 016. Additionally, the agency is proposing to revise the title of MS-DRG 016 from “Autologous Bone Marrow Transplant with CC/MCC” to “Autologous Bone Marrow Transplant with CC/MCC or T-cell Immunotherapy.”

However, the agency emphasized that it invites public comment on alternative payment approaches for CAR T-cell therapies in the context of the pending, new technology add-on payment applications by the CAR-T drugmakers Novartis Pharmaceuticals and Kite Pharma. If approved in the final rule, the technology add-on payments would provide an additional and separate payment equivalent to up to 50% of the product cost plus the MS-DRG payment received for the episode of care.

Other items in the proposed rule include approximate base payments for hematopoietic stem cell transplantation for fiscal 2019, which starts Oct. 1, 2018. The approximate per unit payment is $5,498, which translates to a total base payment of $64,790 for allogeneic bone marrow transplant (MS-DRG 014) for instance. In an American Society for Blood and Marrow Transplantation blog, Ms. Farnia outlined the approximate base weights and estimated reimbursements calculated from the rule.

CMS did not make any changes to the payment model for allogeneic hematopoietic cell transplantation despite continued requests by physicians for donor acquisition charges. Ms. Farnia encourages doctors to express to CMS the importance of such reimbursement during the comment period.

Public comments on the inpatient payment proposal are due by June 25, 2018, and can be submitted at https://www.regulations.gov. Additionally, CMS will convene a meeting of the Medicare Evidence Development & Coverage Advisory Committee on August 22, 2018, to consider whether to issue a national coverage policy for CAR T-cell therapies that would set consistent parameters for patient access.

Physicians may finally have some clarity on payment for inpatient administration of two chimeric antigen receptor–T-cell therapies if a proposed rule from the Centers of Medicare & Medicaid Services becomes final.

The agency is seeking to assign ICD-10-PCS codes XW033C3 and XW043C3 to the use of axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) in the inpatient setting for fiscal year 2019. The agency is also considering the creation of a new Medicare Severity–Diagnosis Related Group (MS-DRG) code for procedures involving the use of chimeric antigen receptor (CAR) T-cell therapy drugs. The proposal was published in May in the Federal Register.

The proposal demonstrates that CMS is listening to physicians’ concerns about CAR T payments and working to provide a more reasonable framework, said Stephanie Farnia, director of health policy and strategic relations for the American Society for Blood and Marrow Transplantation.

“The primary point of significance is that CAR-T care episodes should be assigned to a specific MS-DRG in FY2019, which will give physicians a clearer sense of inpatient reimbursement in advance,” she said in an interview.

Uncertainty about inpatient payment for administration of the two approved CAR-T therapies have been a lingering concern of specialists using, or interested in using, the therapies. In April 2018, CMS announced payment rates for outpatient administration of the two drugs, settling on $395,380 for axicabtagene ciloleucel and $500,839 for tisagenlecleucel. The two medications have list prices of $373,000 and $475,000, respectively.

However, physicians noted that even if the drugs are first administered in the outpatient setting, inpatient care is likely to occur with CAR T-cell therapies because some patients will need to be admitted in order to be monitored for serious side effects. In such cases, all payments will become part of the inpatient stay per CMS’ 3-day payment window rule.

In outlining the most recent payment proposal, CMS stated that its clinical advisers believe that patients receiving treatment with CAR T-cell therapy would have similar clinical characteristics and comorbidities as patients treated with autologous bone marrow transplant therapy, who are currently assigned to MS-DRG 016 “Autologous Bone Marrow Transplant with CC/MCC”. Therefore, CMS officials said they are suggesting ICD-10-PCS procedure codes XW033C3 and XW043C3 to pre-MDC MS-DRG 016. Additionally, the agency is proposing to revise the title of MS-DRG 016 from “Autologous Bone Marrow Transplant with CC/MCC” to “Autologous Bone Marrow Transplant with CC/MCC or T-cell Immunotherapy.”

However, the agency emphasized that it invites public comment on alternative payment approaches for CAR T-cell therapies in the context of the pending, new technology add-on payment applications by the CAR-T drugmakers Novartis Pharmaceuticals and Kite Pharma. If approved in the final rule, the technology add-on payments would provide an additional and separate payment equivalent to up to 50% of the product cost plus the MS-DRG payment received for the episode of care.

Other items in the proposed rule include approximate base payments for hematopoietic stem cell transplantation for fiscal 2019, which starts Oct. 1, 2018. The approximate per unit payment is $5,498, which translates to a total base payment of $64,790 for allogeneic bone marrow transplant (MS-DRG 014) for instance. In an American Society for Blood and Marrow Transplantation blog, Ms. Farnia outlined the approximate base weights and estimated reimbursements calculated from the rule.

CMS did not make any changes to the payment model for allogeneic hematopoietic cell transplantation despite continued requests by physicians for donor acquisition charges. Ms. Farnia encourages doctors to express to CMS the importance of such reimbursement during the comment period.

Public comments on the inpatient payment proposal are due by June 25, 2018, and can be submitted at https://www.regulations.gov. Additionally, CMS will convene a meeting of the Medicare Evidence Development & Coverage Advisory Committee on August 22, 2018, to consider whether to issue a national coverage policy for CAR T-cell therapies that would set consistent parameters for patient access.

NEWPORT BEACH, CALIF. – A revised hematopoietic stem cell transplantation comorbidity index developed for adolescents and young adults is useful for predicting nonrelapse mortality in this specific population, according to Brian Friend, MD.

In a retrospective study of 241 patients aged 15-39 years who underwent a first allogeneic hematopoietic stem cell transplant (HCT) between 2005 and 2015 at the University of California, Los Angeles, nonrelapse mortality incidence was particularly high, with rates of 26%, 28%, and 30% at 1, 2, and 3 years, respectively, Dr. Friend, a clinical research fellow at the David Geffen School of Medicine, Los Angeles, reported in a poster at the Acute Leukemia Forum of Hemedicus.

Sharon Worcester/MDedge News

“We sought to develop a modified HCT-CI that would be more practical and efficient in predicting outcomes of adolescent and young adult patients,” he wrote.

Data were collected on 15 comorbidities included in the original HCT-CI study, as well as the psychosocial risk factors. The relationship between multiple variables and the incidence of nonrelapse mortality was investigated via the Fine and Gray competing risk model with adjustments for patient- and transplant-specific factors.

A few things were “looked at differently,” he said, explaining, for example, that multiple cardiovascular risk factors were combined into one since they are rare in younger patients.

The study demonstrated that an index including only a few comorbidities important in adolescents and young adults is more predictive in these younger patients vs. adults, suggesting that a simpler model is more practical and useful, Dr. Friend said.

A larger study is planned in conjunction with the Center for International Blood and Marrow Transplant Research (CIBMTR). The researchers for that study will take an in-depth look at this younger population in an effort to develop a novel risk score for them. Other future efforts will focus on developing interventions to target high risk patients – and in particular, modifiable risk factors – with a focus on preventive measures, he said.

Dr. Friend reported having no financial disclosures.

[email protected]

NEWPORT BEACH, CALIF. – A revised hematopoietic stem cell transplantation comorbidity index developed for adolescents and young adults is useful for predicting nonrelapse mortality in this specific population, according to Brian Friend, MD.

In a retrospective study of 241 patients aged 15-39 years who underwent a first allogeneic hematopoietic stem cell transplant (HCT) between 2005 and 2015 at the University of California, Los Angeles, nonrelapse mortality incidence was particularly high, with rates of 26%, 28%, and 30% at 1, 2, and 3 years, respectively, Dr. Friend, a clinical research fellow at the David Geffen School of Medicine, Los Angeles, reported in a poster at the Acute Leukemia Forum of Hemedicus.

Sharon Worcester/MDedge News

“We sought to develop a modified HCT-CI that would be more practical and efficient in predicting outcomes of adolescent and young adult patients,” he wrote.

Data were collected on 15 comorbidities included in the original HCT-CI study, as well as the psychosocial risk factors. The relationship between multiple variables and the incidence of nonrelapse mortality was investigated via the Fine and Gray competing risk model with adjustments for patient- and transplant-specific factors.

A few things were “looked at differently,” he said, explaining, for example, that multiple cardiovascular risk factors were combined into one since they are rare in younger patients.

The study demonstrated that an index including only a few comorbidities important in adolescents and young adults is more predictive in these younger patients vs. adults, suggesting that a simpler model is more practical and useful, Dr. Friend said.

A larger study is planned in conjunction with the Center for International Blood and Marrow Transplant Research (CIBMTR). The researchers for that study will take an in-depth look at this younger population in an effort to develop a novel risk score for them. Other future efforts will focus on developing interventions to target high risk patients – and in particular, modifiable risk factors – with a focus on preventive measures, he said.

Dr. Friend reported having no financial disclosures.

[email protected]

NEWPORT BEACH, CALIF. – A revised hematopoietic stem cell transplantation comorbidity index developed for adolescents and young adults is useful for predicting nonrelapse mortality in this specific population, according to Brian Friend, MD.

In a retrospective study of 241 patients aged 15-39 years who underwent a first allogeneic hematopoietic stem cell transplant (HCT) between 2005 and 2015 at the University of California, Los Angeles, nonrelapse mortality incidence was particularly high, with rates of 26%, 28%, and 30% at 1, 2, and 3 years, respectively, Dr. Friend, a clinical research fellow at the David Geffen School of Medicine, Los Angeles, reported in a poster at the Acute Leukemia Forum of Hemedicus.

Sharon Worcester/MDedge News

“We sought to develop a modified HCT-CI that would be more practical and efficient in predicting outcomes of adolescent and young adult patients,” he wrote.

Data were collected on 15 comorbidities included in the original HCT-CI study, as well as the psychosocial risk factors. The relationship between multiple variables and the incidence of nonrelapse mortality was investigated via the Fine and Gray competing risk model with adjustments for patient- and transplant-specific factors.

A few things were “looked at differently,” he said, explaining, for example, that multiple cardiovascular risk factors were combined into one since they are rare in younger patients.

The study demonstrated that an index including only a few comorbidities important in adolescents and young adults is more predictive in these younger patients vs. adults, suggesting that a simpler model is more practical and useful, Dr. Friend said.

A larger study is planned in conjunction with the Center for International Blood and Marrow Transplant Research (CIBMTR). The researchers for that study will take an in-depth look at this younger population in an effort to develop a novel risk score for them. Other future efforts will focus on developing interventions to target high risk patients – and in particular, modifiable risk factors – with a focus on preventive measures, he said.

Dr. Friend reported having no financial disclosures.

[email protected]

SALT LAKE CITY – The presence of p2X7 receptor single nucleotide polymorphisms (SNPs) associated with gain and loss of function may help predict outcomes after allogeneic stem cell transplantation, according to findings from a clinical correlate analysis of recipient and donor DNA samples.

The findings require validation in future studies, but suggest that the presence of the SNPs and p2X7 haplotypes 2 and 4 could be incorporated into disease risk models to improve transplant decision making, David Stuart Ritchie, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The analysis, which specifically looked for the presence of 16 previously identified SNPs and the haplotypes 2 and 4 in p2x7, was performed on pretransplant DNA samples from 333 allogeneic stem cell transplant recipients and 228 donors at a single center between 2002 and 2013. The findings were correlated with patient outcomes.

Five SNPs were excluded from correlation because of low frequency, and of the 11 remaining SNPs, 3 were found to be significantly associated with reduced incidence of acute and/or chronic graft-versus-host disease (GVHD), and 2 were significantly associated with increased relapse or transplant-related mortality, said Dr. Ritchie of the University of Melbourne, Parkville, Australia.

The loss-of-function SNPs rs28360457 and rs3751133 – each linked with decreased inflammation – were significantly associated with a reduced incidence of acute GVHD when comparing grade 0 with grades 1-4 GVHD (P = .0234 and P = .0411, respectively), but not when comparing grades 0-1 and grades 2-4 GVHD.

SNP rs3751133 was also significantly associated with reduced incidence of chronic GVHD when comparing grade 0 with grades 0-4 GVHD (P = .01), but not when comparing grades 0-1 and grades 2-4 GVHD, he said.

The loss-of-function SNP rs1653624 – which is linked with decreased phagocytosis – was associated with an increased incidence of acute GVHD when comparing grade 0 vs. grade 1-4 GVHD (P = .01), but not when comparing grades 0-1 and grades 2-4 GVHD (P = NS).

Sharon Worcester/MDedge News

[email protected]

SOURCE: Koldej R et al. The 2018 BMT Tandem Meetings, Abstract 22.

SALT LAKE CITY – The presence of p2X7 receptor single nucleotide polymorphisms (SNPs) associated with gain and loss of function may help predict outcomes after allogeneic stem cell transplantation, according to findings from a clinical correlate analysis of recipient and donor DNA samples.

The findings require validation in future studies, but suggest that the presence of the SNPs and p2X7 haplotypes 2 and 4 could be incorporated into disease risk models to improve transplant decision making, David Stuart Ritchie, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The analysis, which specifically looked for the presence of 16 previously identified SNPs and the haplotypes 2 and 4 in p2x7, was performed on pretransplant DNA samples from 333 allogeneic stem cell transplant recipients and 228 donors at a single center between 2002 and 2013. The findings were correlated with patient outcomes.

Five SNPs were excluded from correlation because of low frequency, and of the 11 remaining SNPs, 3 were found to be significantly associated with reduced incidence of acute and/or chronic graft-versus-host disease (GVHD), and 2 were significantly associated with increased relapse or transplant-related mortality, said Dr. Ritchie of the University of Melbourne, Parkville, Australia.

The loss-of-function SNPs rs28360457 and rs3751133 – each linked with decreased inflammation – were significantly associated with a reduced incidence of acute GVHD when comparing grade 0 with grades 1-4 GVHD (P = .0234 and P = .0411, respectively), but not when comparing grades 0-1 and grades 2-4 GVHD.

SNP rs3751133 was also significantly associated with reduced incidence of chronic GVHD when comparing grade 0 with grades 0-4 GVHD (P = .01), but not when comparing grades 0-1 and grades 2-4 GVHD, he said.

The loss-of-function SNP rs1653624 – which is linked with decreased phagocytosis – was associated with an increased incidence of acute GVHD when comparing grade 0 vs. grade 1-4 GVHD (P = .01), but not when comparing grades 0-1 and grades 2-4 GVHD (P = NS).

Sharon Worcester/MDedge News

[email protected]

SOURCE: Koldej R et al. The 2018 BMT Tandem Meetings, Abstract 22.

SALT LAKE CITY – The presence of p2X7 receptor single nucleotide polymorphisms (SNPs) associated with gain and loss of function may help predict outcomes after allogeneic stem cell transplantation, according to findings from a clinical correlate analysis of recipient and donor DNA samples.

The findings require validation in future studies, but suggest that the presence of the SNPs and p2X7 haplotypes 2 and 4 could be incorporated into disease risk models to improve transplant decision making, David Stuart Ritchie, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The analysis, which specifically looked for the presence of 16 previously identified SNPs and the haplotypes 2 and 4 in p2x7, was performed on pretransplant DNA samples from 333 allogeneic stem cell transplant recipients and 228 donors at a single center between 2002 and 2013. The findings were correlated with patient outcomes.

Five SNPs were excluded from correlation because of low frequency, and of the 11 remaining SNPs, 3 were found to be significantly associated with reduced incidence of acute and/or chronic graft-versus-host disease (GVHD), and 2 were significantly associated with increased relapse or transplant-related mortality, said Dr. Ritchie of the University of Melbourne, Parkville, Australia.

The loss-of-function SNPs rs28360457 and rs3751133 – each linked with decreased inflammation – were significantly associated with a reduced incidence of acute GVHD when comparing grade 0 with grades 1-4 GVHD (P = .0234 and P = .0411, respectively), but not when comparing grades 0-1 and grades 2-4 GVHD.

SNP rs3751133 was also significantly associated with reduced incidence of chronic GVHD when comparing grade 0 with grades 0-4 GVHD (P = .01), but not when comparing grades 0-1 and grades 2-4 GVHD, he said.

The loss-of-function SNP rs1653624 – which is linked with decreased phagocytosis – was associated with an increased incidence of acute GVHD when comparing grade 0 vs. grade 1-4 GVHD (P = .01), but not when comparing grades 0-1 and grades 2-4 GVHD (P = NS).

Sharon Worcester/MDedge News

[email protected]

SOURCE: Koldej R et al. The 2018 BMT Tandem Meetings, Abstract 22.

SALT LAKE CITY – Comprehensive assessment of functional status and endurance prior to allogeneic hematopoietic cell transplantation (HCT) provides important insights into posttransplant outcomes, and when used in combination with other measures may improve the patient selection process, a chart review suggests.

In 349 patients, results of the prospective assessment of physical performance and endurance, along with HCT Comorbidity Index (HCT-CI) score and Karnofsky Performance Scale score (KPS), were compared with day 100-plus nonrelapse mortality and overall survival. The measures were also compared with the novel measures of hospital length of stay, and death during HCT admission, Shabnam Rehman, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

FatCamera/Getty Images

“Similarly, patients who are able to perform at least 11 sit-to-stands in 30 seconds are more likely to be discharged earlier (63% vs. 14% discharged within 30 days),” she said. “The converse is also true.”

That is, only 16% of those not able to recover their heart rate within 3 minutes had a 30-day or shorter stay, while 31% had at least a 60-day stay. In addition, just 13% of those with limited endurance had a 30-day stay or shorter, while 24% had at least a 60-day stay, she explained.

Further, patients with limited endurance, and those unable to perform 10 or more sit-to-stands in 30 seconds were more likely to die during their first transplant admission. Of those with limited endurance, 31% died during admission and 13% survived, and of those with good endurance 69% died during admission and 87% survived. Among patients who were unable to perform more than 10 sit-to-stands, 42% died during admission and 20% survived, and of those able to perform 11 or more, 38% died during admission, and 53% survived.

Overall survival was associated with age, KPS, HCT-CI, and age-adjusted HCT-CI, she noted.

“Patients who were over age 40 and more, and patients with a KPS of 60 or 70, belong to the high- to intermediate-risk group more likely to have decreased overall survival as has been shown in previous studies,” she said. “In addition to validating these findings, we also found that the semiquantitative measures, including pain and endurance, were also associated with overall survival.”

Those with pain present or limited endurance had significantly poorer overall survival (P = .007 and P = .01, respectively), and this finding was reflected in the quantitative measures of sit-to-stands (P = .01) and step-ups (P = .001), even when stratified by age-adjusted HCT-CI, she said.

In addition, a number of risk factors present at the pretreatment assessment were found to be significantly associated with requirement of an assistive device at discharge. These included pain, weakness in the lower extremities, use of an assistive device, inability to perform 25 step-ups and more than 10 sit-to-stands in 30 seconds, and limited endurance (P values ranging from .02 to less than .0001). Requirement of a device was associated with poorer overall survival (P = .03), she said.

Study participants were adults aged 18 years and older (median, 58 years) undergoing a first allogeneic HCT at a single center between 2010 and 2016. Most (83%) were older than age 40 years and 58% were men. About half (51%) had acute myeloid leukemia, and 64% overall had a KPS score of 60-70.

Physical therapists assessed physical performance of all patients within 4 weeks pre-HCT; testing included 25 7-inch step-ups on each side, unassisted sit-to-stands from an 18-inch chair in 30 seconds, weight-bearing ability, need for assistance with ambulation, motor strength in four extremities, sensory or coordination impairment, self-reported pain, and time to recovery of heart rate and oxygen saturation to pre-exercise levels.

“The HCT-CI is a validated tool that predicts nonrelapse mortality and overall survival, but comorbidity alone as a single domain is not a surrogate of overall health or reflection on the true biological age of our patients,” Dr. Rehman said, noting that studies have shown that functional impairment is associated with shorter overall survival, and that patient-reported physical functioning is predictive of overall survival. “The assessment of functional impairment becomes more critical given the aging U.S. population and older patients receiving transplant.”

Traditionally, functional status has been assessed via the KPS, which is a subjective measure and lacks precision, and the HCT-CI has not been studied in the context of the novel outcome measures addressed in the current study, she noted.

The current findings highlight the prognostic value of a more quantitative pretransplant assessment, which can help improve the patient selection process.

“We are in the process of analyzing some more outcomes of these pretransplant assessments, and developing a score that can, in conjunction with other predictive tools, help us improve pretransplant risk stratification and devise interventions that can improve the endurance and overall survival of the patients,” she concluded.

Dr. Rehman reported having no financial disclosures.

[email protected]

SOURCE: Rehman S et al., The 2018 BTM Tandem Meetings, Abstract 19.

SALT LAKE CITY – Comprehensive assessment of functional status and endurance prior to allogeneic hematopoietic cell transplantation (HCT) provides important insights into posttransplant outcomes, and when used in combination with other measures may improve the patient selection process, a chart review suggests.

In 349 patients, results of the prospective assessment of physical performance and endurance, along with HCT Comorbidity Index (HCT-CI) score and Karnofsky Performance Scale score (KPS), were compared with day 100-plus nonrelapse mortality and overall survival. The measures were also compared with the novel measures of hospital length of stay, and death during HCT admission, Shabnam Rehman, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

FatCamera/Getty Images

“Similarly, patients who are able to perform at least 11 sit-to-stands in 30 seconds are more likely to be discharged earlier (63% vs. 14% discharged within 30 days),” she said. “The converse is also true.”

That is, only 16% of those not able to recover their heart rate within 3 minutes had a 30-day or shorter stay, while 31% had at least a 60-day stay. In addition, just 13% of those with limited endurance had a 30-day stay or shorter, while 24% had at least a 60-day stay, she explained.

Further, patients with limited endurance, and those unable to perform 10 or more sit-to-stands in 30 seconds were more likely to die during their first transplant admission. Of those with limited endurance, 31% died during admission and 13% survived, and of those with good endurance 69% died during admission and 87% survived. Among patients who were unable to perform more than 10 sit-to-stands, 42% died during admission and 20% survived, and of those able to perform 11 or more, 38% died during admission, and 53% survived.

Overall survival was associated with age, KPS, HCT-CI, and age-adjusted HCT-CI, she noted.

“Patients who were over age 40 and more, and patients with a KPS of 60 or 70, belong to the high- to intermediate-risk group more likely to have decreased overall survival as has been shown in previous studies,” she said. “In addition to validating these findings, we also found that the semiquantitative measures, including pain and endurance, were also associated with overall survival.”

Those with pain present or limited endurance had significantly poorer overall survival (P = .007 and P = .01, respectively), and this finding was reflected in the quantitative measures of sit-to-stands (P = .01) and step-ups (P = .001), even when stratified by age-adjusted HCT-CI, she said.

In addition, a number of risk factors present at the pretreatment assessment were found to be significantly associated with requirement of an assistive device at discharge. These included pain, weakness in the lower extremities, use of an assistive device, inability to perform 25 step-ups and more than 10 sit-to-stands in 30 seconds, and limited endurance (P values ranging from .02 to less than .0001). Requirement of a device was associated with poorer overall survival (P = .03), she said.

Study participants were adults aged 18 years and older (median, 58 years) undergoing a first allogeneic HCT at a single center between 2010 and 2016. Most (83%) were older than age 40 years and 58% were men. About half (51%) had acute myeloid leukemia, and 64% overall had a KPS score of 60-70.

Physical therapists assessed physical performance of all patients within 4 weeks pre-HCT; testing included 25 7-inch step-ups on each side, unassisted sit-to-stands from an 18-inch chair in 30 seconds, weight-bearing ability, need for assistance with ambulation, motor strength in four extremities, sensory or coordination impairment, self-reported pain, and time to recovery of heart rate and oxygen saturation to pre-exercise levels.

“The HCT-CI is a validated tool that predicts nonrelapse mortality and overall survival, but comorbidity alone as a single domain is not a surrogate of overall health or reflection on the true biological age of our patients,” Dr. Rehman said, noting that studies have shown that functional impairment is associated with shorter overall survival, and that patient-reported physical functioning is predictive of overall survival. “The assessment of functional impairment becomes more critical given the aging U.S. population and older patients receiving transplant.”

Traditionally, functional status has been assessed via the KPS, which is a subjective measure and lacks precision, and the HCT-CI has not been studied in the context of the novel outcome measures addressed in the current study, she noted.

The current findings highlight the prognostic value of a more quantitative pretransplant assessment, which can help improve the patient selection process.

“We are in the process of analyzing some more outcomes of these pretransplant assessments, and developing a score that can, in conjunction with other predictive tools, help us improve pretransplant risk stratification and devise interventions that can improve the endurance and overall survival of the patients,” she concluded.

Dr. Rehman reported having no financial disclosures.

[email protected]

SOURCE: Rehman S et al., The 2018 BTM Tandem Meetings, Abstract 19.

SALT LAKE CITY – Comprehensive assessment of functional status and endurance prior to allogeneic hematopoietic cell transplantation (HCT) provides important insights into posttransplant outcomes, and when used in combination with other measures may improve the patient selection process, a chart review suggests.

In 349 patients, results of the prospective assessment of physical performance and endurance, along with HCT Comorbidity Index (HCT-CI) score and Karnofsky Performance Scale score (KPS), were compared with day 100-plus nonrelapse mortality and overall survival. The measures were also compared with the novel measures of hospital length of stay, and death during HCT admission, Shabnam Rehman, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

FatCamera/Getty Images

“Similarly, patients who are able to perform at least 11 sit-to-stands in 30 seconds are more likely to be discharged earlier (63% vs. 14% discharged within 30 days),” she said. “The converse is also true.”

That is, only 16% of those not able to recover their heart rate within 3 minutes had a 30-day or shorter stay, while 31% had at least a 60-day stay. In addition, just 13% of those with limited endurance had a 30-day stay or shorter, while 24% had at least a 60-day stay, she explained.

Further, patients with limited endurance, and those unable to perform 10 or more sit-to-stands in 30 seconds were more likely to die during their first transplant admission. Of those with limited endurance, 31% died during admission and 13% survived, and of those with good endurance 69% died during admission and 87% survived. Among patients who were unable to perform more than 10 sit-to-stands, 42% died during admission and 20% survived, and of those able to perform 11 or more, 38% died during admission, and 53% survived.

Overall survival was associated with age, KPS, HCT-CI, and age-adjusted HCT-CI, she noted.

“Patients who were over age 40 and more, and patients with a KPS of 60 or 70, belong to the high- to intermediate-risk group more likely to have decreased overall survival as has been shown in previous studies,” she said. “In addition to validating these findings, we also found that the semiquantitative measures, including pain and endurance, were also associated with overall survival.”

Those with pain present or limited endurance had significantly poorer overall survival (P = .007 and P = .01, respectively), and this finding was reflected in the quantitative measures of sit-to-stands (P = .01) and step-ups (P = .001), even when stratified by age-adjusted HCT-CI, she said.

In addition, a number of risk factors present at the pretreatment assessment were found to be significantly associated with requirement of an assistive device at discharge. These included pain, weakness in the lower extremities, use of an assistive device, inability to perform 25 step-ups and more than 10 sit-to-stands in 30 seconds, and limited endurance (P values ranging from .02 to less than .0001). Requirement of a device was associated with poorer overall survival (P = .03), she said.

Study participants were adults aged 18 years and older (median, 58 years) undergoing a first allogeneic HCT at a single center between 2010 and 2016. Most (83%) were older than age 40 years and 58% were men. About half (51%) had acute myeloid leukemia, and 64% overall had a KPS score of 60-70.

Physical therapists assessed physical performance of all patients within 4 weeks pre-HCT; testing included 25 7-inch step-ups on each side, unassisted sit-to-stands from an 18-inch chair in 30 seconds, weight-bearing ability, need for assistance with ambulation, motor strength in four extremities, sensory or coordination impairment, self-reported pain, and time to recovery of heart rate and oxygen saturation to pre-exercise levels.

“The HCT-CI is a validated tool that predicts nonrelapse mortality and overall survival, but comorbidity alone as a single domain is not a surrogate of overall health or reflection on the true biological age of our patients,” Dr. Rehman said, noting that studies have shown that functional impairment is associated with shorter overall survival, and that patient-reported physical functioning is predictive of overall survival. “The assessment of functional impairment becomes more critical given the aging U.S. population and older patients receiving transplant.”

Traditionally, functional status has been assessed via the KPS, which is a subjective measure and lacks precision, and the HCT-CI has not been studied in the context of the novel outcome measures addressed in the current study, she noted.

The current findings highlight the prognostic value of a more quantitative pretransplant assessment, which can help improve the patient selection process.

“We are in the process of analyzing some more outcomes of these pretransplant assessments, and developing a score that can, in conjunction with other predictive tools, help us improve pretransplant risk stratification and devise interventions that can improve the endurance and overall survival of the patients,” she concluded.

Dr. Rehman reported having no financial disclosures.

[email protected]

SOURCE: Rehman S et al., The 2018 BTM Tandem Meetings, Abstract 19.

SALT LAKE CITY – Both male and female recipients of childhood hematopoietic stem cell transplantation (HSCT) were very likely to have severely decreased fertility potential, even in the setting of preserved puberty, according to a recent study of adolescent and young adult HSCT recipients.

A reduced intensity conditioning regimen did not protect this cohort from decreased fertility, a finding that surprised the study’s lead author.

“We had hypothesized that, as compared to myeloablative conditioning, reduced intensity conditioning in children who received HSCT would lower the risk of infertility and lessen gonadal failure,” said Helen Oquendo del Toro, MD. In fact, Dr. Oquendo del Toro and her collaborators found that more than 90% of semen samples available for analysis had results that indicated infertility or severely impaired fertility, regardless of the type of pretransplant conditioning the patient had received.

The study highlights the need for fertility preservation when possible before HSCT, and makes clear that “normal puberty does not equate to normal fertility,” said Dr. Oquendo del Toro, of Cincinnati Children’s Hospital Medical Center.

Dr. Oquendo del Toro presented results of an observational cohort study of late effects of HSCT that included individuals aged 1-40 years old who received a single HSCT at, or after, 1 year of age.

Twenty-one males in the study had semen available for analysis. Of the 10 males who received myeloablative conditioning (MAC), 8 had azoospermia, and 2 more had oligoteratospermia (low sperm count with abnormal morphology). For the 11 males who received reduced intensity conditioning (RIC), eight had azoospermia, two had semen samples that showed oligoteratospermia, and one had a normal semen analysis.

The median age at transplant for these males was 14.5 years, and patients were a median of 19 years old at follow-up, Dr. Oquendo del Toro said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

[email protected]

SOURCE: Oquendo del Toro H et al. The 2018 BMT Tandem Meetings, Abstract 88.

SALT LAKE CITY – Both male and female recipients of childhood hematopoietic stem cell transplantation (HSCT) were very likely to have severely decreased fertility potential, even in the setting of preserved puberty, according to a recent study of adolescent and young adult HSCT recipients.

A reduced intensity conditioning regimen did not protect this cohort from decreased fertility, a finding that surprised the study’s lead author.

“We had hypothesized that, as compared to myeloablative conditioning, reduced intensity conditioning in children who received HSCT would lower the risk of infertility and lessen gonadal failure,” said Helen Oquendo del Toro, MD. In fact, Dr. Oquendo del Toro and her collaborators found that more than 90% of semen samples available for analysis had results that indicated infertility or severely impaired fertility, regardless of the type of pretransplant conditioning the patient had received.

The study highlights the need for fertility preservation when possible before HSCT, and makes clear that “normal puberty does not equate to normal fertility,” said Dr. Oquendo del Toro, of Cincinnati Children’s Hospital Medical Center.

Dr. Oquendo del Toro presented results of an observational cohort study of late effects of HSCT that included individuals aged 1-40 years old who received a single HSCT at, or after, 1 year of age.

Twenty-one males in the study had semen available for analysis. Of the 10 males who received myeloablative conditioning (MAC), 8 had azoospermia, and 2 more had oligoteratospermia (low sperm count with abnormal morphology). For the 11 males who received reduced intensity conditioning (RIC), eight had azoospermia, two had semen samples that showed oligoteratospermia, and one had a normal semen analysis.

The median age at transplant for these males was 14.5 years, and patients were a median of 19 years old at follow-up, Dr. Oquendo del Toro said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

[email protected]

SOURCE: Oquendo del Toro H et al. The 2018 BMT Tandem Meetings, Abstract 88.

SALT LAKE CITY – Both male and female recipients of childhood hematopoietic stem cell transplantation (HSCT) were very likely to have severely decreased fertility potential, even in the setting of preserved puberty, according to a recent study of adolescent and young adult HSCT recipients.

A reduced intensity conditioning regimen did not protect this cohort from decreased fertility, a finding that surprised the study’s lead author.

“We had hypothesized that, as compared to myeloablative conditioning, reduced intensity conditioning in children who received HSCT would lower the risk of infertility and lessen gonadal failure,” said Helen Oquendo del Toro, MD. In fact, Dr. Oquendo del Toro and her collaborators found that more than 90% of semen samples available for analysis had results that indicated infertility or severely impaired fertility, regardless of the type of pretransplant conditioning the patient had received.

The study highlights the need for fertility preservation when possible before HSCT, and makes clear that “normal puberty does not equate to normal fertility,” said Dr. Oquendo del Toro, of Cincinnati Children’s Hospital Medical Center.

Dr. Oquendo del Toro presented results of an observational cohort study of late effects of HSCT that included individuals aged 1-40 years old who received a single HSCT at, or after, 1 year of age.

Twenty-one males in the study had semen available for analysis. Of the 10 males who received myeloablative conditioning (MAC), 8 had azoospermia, and 2 more had oligoteratospermia (low sperm count with abnormal morphology). For the 11 males who received reduced intensity conditioning (RIC), eight had azoospermia, two had semen samples that showed oligoteratospermia, and one had a normal semen analysis.

The median age at transplant for these males was 14.5 years, and patients were a median of 19 years old at follow-up, Dr. Oquendo del Toro said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

[email protected]

SOURCE: Oquendo del Toro H et al. The 2018 BMT Tandem Meetings, Abstract 88.

The next major approval in the chimeric antigen receptor (CAR) T-cell therapy arena will target multiple myeloma, and will “completely transform oncology,” according to Carl June, MD.

That approval is anticipated sometime in 2019.

“Myeloma is the most common blood cancer in adults, and there’s never been a curative therapy, but now there is a subset of patients who look like they’re cured with CAR T cells,” Dr. June, the Richard W. Vague Professor in Immunotherapy and a pioneer in CAR T-cell research at the University of Pennsylvania, Philadelphia, said in an interview.

The first treated patient in a trial of a novel anti-B-cell maturation antigen (BCMA)-specific CAR T-cell therapy (CART-BCMA) developed by University of Pennsylvania researchers in collaboration with Novartis is part of that subset.

Woodring Wright, MD, a professor of cell biology and medicine at the University of Texas Southwestern Medical Center (UT Southwestern) in Dallas recently outed himself as that first patient, announcing in a Feb. 14, 2018, UT Southwestern press report that CART-BCMA saved his life.

Dr. Wright, who holds the Southland Financial Corporation Distinguished Chair in Geriatrics at UT Southwestern, was diagnosed with multiple myeloma about 12 years ago and failed 11 prior chemotherapies before he was enrolled in the CART-BCMA trial.

“Now he considers himself cured,” Dr. June said.

Sharon Worcester/MDedge News

[email protected]

The next major approval in the chimeric antigen receptor (CAR) T-cell therapy arena will target multiple myeloma, and will “completely transform oncology,” according to Carl June, MD.

That approval is anticipated sometime in 2019.

“Myeloma is the most common blood cancer in adults, and there’s never been a curative therapy, but now there is a subset of patients who look like they’re cured with CAR T cells,” Dr. June, the Richard W. Vague Professor in Immunotherapy and a pioneer in CAR T-cell research at the University of Pennsylvania, Philadelphia, said in an interview.

The first treated patient in a trial of a novel anti-B-cell maturation antigen (BCMA)-specific CAR T-cell therapy (CART-BCMA) developed by University of Pennsylvania researchers in collaboration with Novartis is part of that subset.

Woodring Wright, MD, a professor of cell biology and medicine at the University of Texas Southwestern Medical Center (UT Southwestern) in Dallas recently outed himself as that first patient, announcing in a Feb. 14, 2018, UT Southwestern press report that CART-BCMA saved his life.

Dr. Wright, who holds the Southland Financial Corporation Distinguished Chair in Geriatrics at UT Southwestern, was diagnosed with multiple myeloma about 12 years ago and failed 11 prior chemotherapies before he was enrolled in the CART-BCMA trial.

“Now he considers himself cured,” Dr. June said.

Sharon Worcester/MDedge News

[email protected]

The next major approval in the chimeric antigen receptor (CAR) T-cell therapy arena will target multiple myeloma, and will “completely transform oncology,” according to Carl June, MD.

That approval is anticipated sometime in 2019.

“Myeloma is the most common blood cancer in adults, and there’s never been a curative therapy, but now there is a subset of patients who look like they’re cured with CAR T cells,” Dr. June, the Richard W. Vague Professor in Immunotherapy and a pioneer in CAR T-cell research at the University of Pennsylvania, Philadelphia, said in an interview.

The first treated patient in a trial of a novel anti-B-cell maturation antigen (BCMA)-specific CAR T-cell therapy (CART-BCMA) developed by University of Pennsylvania researchers in collaboration with Novartis is part of that subset.

Woodring Wright, MD, a professor of cell biology and medicine at the University of Texas Southwestern Medical Center (UT Southwestern) in Dallas recently outed himself as that first patient, announcing in a Feb. 14, 2018, UT Southwestern press report that CART-BCMA saved his life.

Dr. Wright, who holds the Southland Financial Corporation Distinguished Chair in Geriatrics at UT Southwestern, was diagnosed with multiple myeloma about 12 years ago and failed 11 prior chemotherapies before he was enrolled in the CART-BCMA trial.

“Now he considers himself cured,” Dr. June said.

Sharon Worcester/MDedge News

[email protected]

NEWPORT BEACH, CALIF. – Use of atovaquone or pentamidine for Pneumocystis jiroveci pneumonia (PJP) prophylaxis was associated with an increased incidence of nocardiosis in allogeneic hematopoietic stem call transplant (HSCT) recipients at the University of California, Los Angeles, according to a review of patient records.

Of 10 cases of late-onset nocardiosis identified among patients who received HSCT between Jan. 1, 2000, and Aug. 30, 2017, 9 cases occurred in 411 patients (2.2%) treated between 2012 and 2017 – a period of increased use of atovaquone prophylaxis, compared with only 1 in 575 patients (0.17%) treated in the prior 12 years when trimethoprim-sulfamethoxazole (TMP-SMX) was used for prophylaxis, Alfonso Molina reported in a poster at the Acute Leukemia Forum of Hemedicus.

Sharon Worcester/MDedge News

[email protected]

SOURCE: Molina A et al., ALF 2018, Poster Session.

NEWPORT BEACH, CALIF. – Use of atovaquone or pentamidine for Pneumocystis jiroveci pneumonia (PJP) prophylaxis was associated with an increased incidence of nocardiosis in allogeneic hematopoietic stem call transplant (HSCT) recipients at the University of California, Los Angeles, according to a review of patient records.

Of 10 cases of late-onset nocardiosis identified among patients who received HSCT between Jan. 1, 2000, and Aug. 30, 2017, 9 cases occurred in 411 patients (2.2%) treated between 2012 and 2017 – a period of increased use of atovaquone prophylaxis, compared with only 1 in 575 patients (0.17%) treated in the prior 12 years when trimethoprim-sulfamethoxazole (TMP-SMX) was used for prophylaxis, Alfonso Molina reported in a poster at the Acute Leukemia Forum of Hemedicus.

Sharon Worcester/MDedge News

[email protected]

SOURCE: Molina A et al., ALF 2018, Poster Session.

NEWPORT BEACH, CALIF. – Use of atovaquone or pentamidine for Pneumocystis jiroveci pneumonia (PJP) prophylaxis was associated with an increased incidence of nocardiosis in allogeneic hematopoietic stem call transplant (HSCT) recipients at the University of California, Los Angeles, according to a review of patient records.

Of 10 cases of late-onset nocardiosis identified among patients who received HSCT between Jan. 1, 2000, and Aug. 30, 2017, 9 cases occurred in 411 patients (2.2%) treated between 2012 and 2017 – a period of increased use of atovaquone prophylaxis, compared with only 1 in 575 patients (0.17%) treated in the prior 12 years when trimethoprim-sulfamethoxazole (TMP-SMX) was used for prophylaxis, Alfonso Molina reported in a poster at the Acute Leukemia Forum of Hemedicus.

Sharon Worcester/MDedge News

[email protected]

SOURCE: Molina A et al., ALF 2018, Poster Session.

SALT LAKE CITY – Recipients of hematopoietic cell transplant with umbilical cord blood CD34+ cells expanded with an aryl hydrocarbon receptor (AHR) antagonist had a significantly higher rate of engraftment and comparable survival to a historical cohort of umbilical cord blood recipients.

The robust expansion of donor umbilical cord blood seen with the new technique opens the door for better use of umbilical cord blood inventory with superior human leukocyte antigen (HLA) matching, John Wagner, MD, said at a top abstracts session of the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The new technique still shared the benefits of low rates of graft-versus-host disease (GVHD) and high survival that have been seen in previous umbilical cord blood transplants, with no significant difference in overall survival, relapse, or acute or chronic GVHD.

Compared to historical controls (n = 151), patients receiving the AHR antagonist–expanded umbilical cord blood (UCB) cells with myeloablative conditioning (n = 9) saw complete and more rapid engraftment (100% vs. 89% engraftment at a median 14 days vs. 23 days; P less than .01), reported Dr. Wagner of the University of Minnesota, Minneapolis.

These and other results came from two arms of a phase 2 trial of MGTA-456 (the working name of the AHR-expanded UCB cells). Twenty patients were to receive MGTA-456 derived from partially matched umbilical cord blood units after either myeloablative or nonmyeloablative conditioning; one patient in each arm had low expansion of UCB, so a total of 18 patients received MGTA-456. Each intervention arm was compared with a historical control arm that had received conventional UCB units.

In the myeloablative arm, patient demographics and disease characteristics were similar to the control cohort except that the MGTA-456 patients were significantly heavier (93.8 kg vs. 66.7 kg; P less than .04).

[email protected]

SOURCE: Wagner J et al. 2018 BMT Tandem Meetings, Abstract 4.

SALT LAKE CITY – Recipients of hematopoietic cell transplant with umbilical cord blood CD34+ cells expanded with an aryl hydrocarbon receptor (AHR) antagonist had a significantly higher rate of engraftment and comparable survival to a historical cohort of umbilical cord blood recipients.

The robust expansion of donor umbilical cord blood seen with the new technique opens the door for better use of umbilical cord blood inventory with superior human leukocyte antigen (HLA) matching, John Wagner, MD, said at a top abstracts session of the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The new technique still shared the benefits of low rates of graft-versus-host disease (GVHD) and high survival that have been seen in previous umbilical cord blood transplants, with no significant difference in overall survival, relapse, or acute or chronic GVHD.

Compared to historical controls (n = 151), patients receiving the AHR antagonist–expanded umbilical cord blood (UCB) cells with myeloablative conditioning (n = 9) saw complete and more rapid engraftment (100% vs. 89% engraftment at a median 14 days vs. 23 days; P less than .01), reported Dr. Wagner of the University of Minnesota, Minneapolis.

These and other results came from two arms of a phase 2 trial of MGTA-456 (the working name of the AHR-expanded UCB cells). Twenty patients were to receive MGTA-456 derived from partially matched umbilical cord blood units after either myeloablative or nonmyeloablative conditioning; one patient in each arm had low expansion of UCB, so a total of 18 patients received MGTA-456. Each intervention arm was compared with a historical control arm that had received conventional UCB units.

In the myeloablative arm, patient demographics and disease characteristics were similar to the control cohort except that the MGTA-456 patients were significantly heavier (93.8 kg vs. 66.7 kg; P less than .04).

[email protected]

SOURCE: Wagner J et al. 2018 BMT Tandem Meetings, Abstract 4.

SALT LAKE CITY – Recipients of hematopoietic cell transplant with umbilical cord blood CD34+ cells expanded with an aryl hydrocarbon receptor (AHR) antagonist had a significantly higher rate of engraftment and comparable survival to a historical cohort of umbilical cord blood recipients.

The robust expansion of donor umbilical cord blood seen with the new technique opens the door for better use of umbilical cord blood inventory with superior human leukocyte antigen (HLA) matching, John Wagner, MD, said at a top abstracts session of the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The new technique still shared the benefits of low rates of graft-versus-host disease (GVHD) and high survival that have been seen in previous umbilical cord blood transplants, with no significant difference in overall survival, relapse, or acute or chronic GVHD.

Compared to historical controls (n = 151), patients receiving the AHR antagonist–expanded umbilical cord blood (UCB) cells with myeloablative conditioning (n = 9) saw complete and more rapid engraftment (100% vs. 89% engraftment at a median 14 days vs. 23 days; P less than .01), reported Dr. Wagner of the University of Minnesota, Minneapolis.

These and other results came from two arms of a phase 2 trial of MGTA-456 (the working name of the AHR-expanded UCB cells). Twenty patients were to receive MGTA-456 derived from partially matched umbilical cord blood units after either myeloablative or nonmyeloablative conditioning; one patient in each arm had low expansion of UCB, so a total of 18 patients received MGTA-456. Each intervention arm was compared with a historical control arm that had received conventional UCB units.

In the myeloablative arm, patient demographics and disease characteristics were similar to the control cohort except that the MGTA-456 patients were significantly heavier (93.8 kg vs. 66.7 kg; P less than .04).

[email protected]

SOURCE: Wagner J et al. 2018 BMT Tandem Meetings, Abstract 4.