Table 1.
Demographics | Diagnosis and prior treatments | CAR-T-cell therapy and vaccine | Baseline immunologic findings7 | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Study ID1 | Age group (years) | Underlying diagnosis2 | Time HCT to vaccine (months)3 | mAb in 6 months before vaccine4 | CAR-Tx target5 | Approximate time from CAR-Tx to vaccine (years) | Vaccine type6 | IgG, mg/dL8 | CD19+ B-cells /μl | CD4+ T-cells /μl |
Pre-CAR-T cohort | ||||||||||
Pre-1 | 19–60 | ALL | yes | CD19 | IIV4 | 376 | 5 | 236 | ||
Pre-2 | 19–60 | NHL | ≤24 | CD19 | IIV4 | 552 | <1 | 103 | ||
Pre-3 | 61–75 | NHL | ≤24 | yes | CD19 | IIV4 | 592 | <1 | 123 | |
Pre-4 | 61–75 | NHL | yes | CD19 | IIV3-HD | 202 | <1 | 113 | ||
Pre-5 | 19–60 | MM | >24 | BCMA | IIV4 | 46 | 47 | 433 | ||
Pre-6* | 61–75 | MM | yes | BCMA | IIV4 | 21 | 21 | 470 | ||
Pre-7* | 61–75 | MM | >24 | yes | BCMA | IIV4 | 591 | 87 | 436 | |
Post-CAR-T cohort | ||||||||||
Post-1* | 10–18 | ALL | >24 | CD19 | 1–2 | NK | 264 | 2 | 1078 | |
Post-2* | 10–18 | ALL | CD19 | >2 | NK | 653 | 387 | 742 | ||
Post-3* | 19–60 | ALL | >24 | CD19 | 1–2 | IIV4 | 823 | 401 | 392 | |
Post-4 | 19–60 | ALL | >24 | CD19 | 1–2 | ccIIV4 | 371 | 0 | 176 | |
Post-5 | 19–60 | ALL | >24 | CD19 | >2 | IIV4 | 310 | <1 | 152 | |
Post-6* | 19–60 | CLL | CD19 | >2 | ccIIV4 | 334 | 14 | 488 | ||
Post-7 | 61–75 | CLL | CD19 | >2 | IIV4 | 217 | <1 | 480 | ||
Post-8 | 61–75 | CLL | CD19 | 1–2 | IIV3-HD | 286 | 3 | 332 | ||
Post-9 | 19–60 | NHL | CD19 | 1–2 | IIV4 | 527 | <1 | 394 | ||
Post-10 | 19–60 | NHL | CD19 | 1–2 | IIV4 | 416 | 1 | 353 | ||
Post-11 | 19–60 | NHL | >24 | CD19 | >2 | IIV4 | 447 | 95 | 504 | |
Post-12 | 61–75 | NHL | CD19 | 1–2 | IIV4 | 364 | 207 | 303 | ||
Post-13* | 61–75 | NHL | CD19 | >2 | ccIIV4 | 189 | 0 | 501 | ||
Post-14 | 61–75 | NHL | CD19 | 1–2 | IIV | 324 | <1 | 304 | ||
Post-15* | 61–75 | MM | >24 | BCMA | 1–2 | aIIV3 | 290 | 165 | 317 |
For de-identification, certain continuous variables were grouped and other variables are provided as summary measures in the manuscript text. All but two participants were white. Additional information is provided in Tables S1 and S2. Blank fields indicate not applicable. NK indicates not known. Baseline is defined as the day of the baseline blood sample prior to vaccination.
ALL indicates acute lymphoblastic leukemia; CAR-Tx, CAR-T-cell therapy; CLL, chronic lymphocytic leukemia; HCT, hematopoietic cell transplant; mAb, B-cell lineage targeted monoclonal antibody; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; NK, not known.
Vaccine abbreviations: IIV3, trivalent inactivated influenza vaccine; IIV4, quadrivalent inactivated influenza vaccine; HD, high dose; cc, cell culture based; a, adjuvant.
Individuals with an antibody response to at least one vaccine strain are indicated with a *.
All individuals in the pre-CAR-T cohort had relapsed/refractory disease at baseline. All individuals in the post-CAR-T cohort had complete remission or very good partial remission at baseline.
Autologous HCT in 4 individuals in the pre-CAR-T cohort and in 1 individual in the post-CAR-T cohort. Allogeneic HCT in 4 individuals in the post-CAR-T cohort.
Monoclonal antibodies were: blinatumomab, rituximab/polatuzumab or daratumumab.
One individual with NHL received a CD20 targeted CAR-T-cell therapy but is indicated with CD19 for confidentiality.
Vaccine strains were A/Brisbane/02/2018 (H1N1)pdm09-like virus, A/Kansas/14/2017 (H3N2)-like virus, B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) for IIV3, with the addition of a B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage) for IIV4.
Lower limit of normal; IgG, 610 mg/dL; CD19+ B-cells, 100 cells/μL; CD4+ T-cells, 500 cells/μL.
For IgG MM, total IgG was estimated by subtracting the monoclonal component from the gamma region of serum protein electrophoresis. Four individuals received IGRT 3–4 months prior to baseline (Table S2) and had IgG levels between 25 and 450 mg/dL.