196 - Antibodies to Vaccine-preventable Infections After CAR-T Cell Immunotherapy for B Cell Malignancies

Background: Chimeric antigen receptor-modified T (CAR-T) cell immunotherapy for B cell hematologic malignancies results in prolonged B cell depletion. Little is known about the effects of CAR-T cell therapy on pre-existing pathogen-specific humoral immunity.

Methods: We conducted a prospective, cross-sectional study of children and adults treated with CD19- or BCMA-CAR-T cell therapy. Eligible patients were ≥ 6 months post-CAR-T cell infusion and in remission without subsequent chemoimmunotherapy. We measured total immunoglobulin G (IgG), pathogen-specific IgG levels for 12 vaccine-preventable infections, and B cell subsets from blood. Seroprotective antibody titers were based on standard thresholds. We described the proportion of patients with seroprotective titers and tested for associations between clinical factors and seroprotection using generalized estimating equations.

Results: We enrolled 65 patients who received CD19- (n=54) or BCMA- (n=11) CAR-T cell therapy. Seven patients were < 18 years old. Samples were collected a median of 20 months (range, 7-68) after CAR T cell infusion. Seroprotection to vaccine-preventable pathogens was generally comparable to the U.S. population (Fig 1) even though blood CD19+ B cell counts were low (< 20 cells/mm³) in 60% of patients. Among 30 patients without IgG replacement in the prior 16 weeks (4 half-lives of IgG), 27 (90%) had hypogammaglobulinemia. Despite this, these individuals had seroprotection to a median of 67% (IQR, 59%-73%) of tested pathogens (Fig 2A). The proportion of patients with seroprotection was lowest for mumps, hepatitis A and B, H. influenzae type B (Hib), S. pneumoniae, and B. pertussis. Patients receiving BCMA-CAR-T cells had seroprotection to fewer pathogens than those receiving CD19-CAR-T cells (Fig 2B), but the difference did not reach statistical significance (Fig 3). There were no significant differences by other variables.Figure 1. Proportion of CAR-T cell recipients with seroprotection to vaccine-preventable infections compared to the U.S. population, stratified by receipt of IgG replacement in the previous 16 weeks.
Figure 2 A-B. Percentage of pathogens with seroprotective antibody titers among patients without IgG replacement in the previous 16 weeks.
Figure 3. Association of clinical factors with seroprotection to vaccine-preventable infections among patients without IgG replacement in the previous 16 weeks (n=30)


Conclusion: Seroprotection for vaccine-preventable infections after CD19-CAR-T cell therapy was comparable to the general population. BCMA-CAR-T cell recipients may benefit most from replacement IgG. Vaccinations after CAR-T cell therapy should be considered and prioritized for S. pneumoniae, Hib, hepatitis viruses, and B. pertussis.

Presenting Author(s)

• 

  Carla S. Walti, MD

  Dr.
  Fred Hutchinson Cancer Research Center, Seattle, WA
  Basel, Basel-Stadt, Switzerland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

  Slides Slides and Audio

Co-Author(s)

• JM

  Joyce Maalouf, MS, MPH

  Ms.
  Fred Hutchinson Cancer Research Center, Seattle, WA
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• JB

  Jim Boonyaratanakornkit, MD PhD

  Dr.
  Fred Hutchinson Cancer Research Center
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• JK

  Jacob Keane-Candib, n/a

  Mr.
  Fred Hutchinson Cancer Research Center, Seattle, WA
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• JT

  Justin J. Taylor, PhD

  Assistant Professor
  Fred Hutchinson Cancer Research Center / University of Washington, Seattle, WA
  Seattle, Washington

  Disclosure: Vir Biotechnology (Grant/Research Support)
• AH

  Alexandre V. Hirayama, MD

  Dr.
  Fred Hutchinson Cancer Research Center, Seattle, WA
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• MB

  Merav Bar, MD

  Associate Professor / Associate Professor, Division of Medical Oncology
  Fred Hutchinson Cancer Research Center / Department of Medicine University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• RG

  Rebecca A. Gardner, MD

  Associate Professor
  University of Washington / Seattle Children's Hospital / Ben Towne Center for Childhood Cancer Research
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• DG

  Damian J. Green, MD

  Associate Professor
  Fred Hutchinson Cancer Research Center / Seattle Care Cancer Alliance / University of Washington School of Medicine, Seattle, WA
  Seattle, Washington

  Disclosure: Cellectar Biosciences (Grant/Research Support)GSK (Advisor or Review Panel member)Juno Therapeutics (Grant/Research Support, Advisor or Review Panel member, Other Financial or Material Support, Royalities)Seattle Genetics (Grant/Research Support, Advisor or Review Panel member)
• 

  Michael Boeckh, MD PhD

  Member
  Fred Hutchinson Cancer Research Center
  Seattle, Washington

  Disclosure: AlloVir (Consultant)EvrysBio (Advisor or Review Panel member, Other Financial or Material Support, share options)Gilead (Consultant, Grant/Research Support)GSK (Consultant)Helocyte (Advisor or Review Panel member, Shareholder)Lophius (Grant/Research Support)Merck (Consultant, Grant/Research Support)SymBio (Consultant)VirBio (Consultant, Grant/Research Support)
• DM

  David G. Maloney, MD, PhD

  Professor
  Fred Hutchinson Cancer Research Center / Seattle Care Cancer Alliance / University of Washington, Seattle, WA
  Seattle, Washington

  Disclosure: A2 Biotherapeutics (Consultant, Other Financial or Material Support, Stock Options)Bioline Rx (Consultant)Celgene (Consultant, Grant/Research Support)Gilead (Consultant)Juno Therapeutics (Consultant, Research Grant or Support, Other Financial or Material Support, four pending patents, not issued, licensed, no royalities, no licensees)Kite Pharma (Consultant, Grant/Research Support)Novartis (Consultant)Pharmacyclics (Consultant)
• EK

  Elizabeth M. Krantz, MS

  Statistical Research Associate
  Fred Hutch Cancer Research Center
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• CT

  Cameron J. Turtle, MBBS, PhD

  Associate Professor
  Fred Hutchinson Cancer Research Center / Seattle Care Cancer Alliance / University of Washington School of Medicine, Seattle, WA
  Seattle, Washington

  Disclosure: Allogene (Other Financial or Material Support, Ad hoc advisory board (last 12 months))ArsenalBio (Advisor or Review Panel member, Other Financial or Material Support, Stock/options)AstraZeneca (Grant/Research Support, Other Financial or Material Support, Ad hoc advisory board (last 12 months))Caribou Biosciences (Advisor or Review Panel member, Other Financial or Material Support, Stock/options)Century Therapeutics (Advisor or Review Panel member)Eureka Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Stock/options)Juno Therapeutics (Grant/Research Support, Other Financial or Material Support, Patent: Licensed to Juno Therapeutics)Myeloid Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Stock/options)Nektar Therapeutics (Grant/Research Support, Other Financial or Material Support, Ad hoc advisory board (last 12 months))PACT Pharma (Other Financial or Material Support, Ad hoc advisory board (last 12 months))Precision Biosciences (Advisor or Review Panel member, Other Financial or Material Support, Stock/options)TCR2 Therapeutics (Grant/Research Support)T-CURX (Advisor or Review Panel member)
• 

  Joshua A. Hill, MD

  Assistant Professor
  Fred Hutchinson Cancer Research Center; University of Washington
  Seattle, Washington

  Disclosure: Allogene (Consultant)Allovir (Consultant)Gilead (Consultant)Karius (Grant/Research Support, Scientific Research Study Investigator)Takeda (Grant/Research Support, Scientific Research Study Investigator)