VACARME : Analysis of humoral protection at baseline and after vaccination in patients with refractory/relapsed lymphoma and myeloma treated with CD19 and BCMA CAR T-cells.
Year: 2025
Type: conference-abstract
Abstract: Introduction Introduction. CART-cell therapy targeting CD19 and B-cell maturation antigen (BCMA) has improved the prognosis of patients (pts) with relapsed/refractory (R/R) non-hodgkin lymphoma (NHL) and multiple myeloma (MM). Upon sustained remission, infections are major causes of morbidity and mortality, some of which are vaccine-preventable. Still, there are limited evidence on vaccine immunogenicity and seroprotection after CAR T-cell therapy. This explains that the vaccination schedule after CAR T-cell is translated from guidelines used in recipients of hematopoietic stem cell transplantation. This study aims to assess humoral vaccine-induced response after vaccination in comparison with baseline in pts with R/R NHL and MM treated with anti-CD19 or anti-BCMA CAR T-cells. Patients and Methods. Pts eligible for the study had a progression-free survival of 6 months or more after CAR T-cells. Pts who had received infusion of immunoglobulins within the past 2 months were excluded. Samples were collected at the time of lymphodepletion and at least six months after CAR T-cell infusion. The seroprotection rate was defined using pre-established cutoffs (or 4 fold increases after vaccination) of IgG-specific antibodies. Post-vaccination titers were obtained at least one month after the final dose was administered. Results From 509 pts treated by CAR T-cell therapy targeting CD19 and BCMA between 2017 and 2024 in a tertiary department of hematology, we retrospectively included 92 pts who were evaluated for seroprotection levels against diphtheria (D), tetanus (T), Haemophilus influenzae (Hib), hepatitis A (HA) and B viruses (HB), the varicella-zoster virus (VZV), and the measles virus (Mv). Median age was 66 (IQR 58-72) and 64 (54-71) year old for MM and NHL pts, respectively. In MM pts, the median number of previous lines was 3 [IQR 3-5], among whom 76% (n=19/25) had received an autologous stem cell transplantation (ASCT). In NHL pts the median number of previous lines was 2 [IQR 1-3], among whom 21% (n=15/68) had received an ASCT. Forty-five pts received a three-dose revaccination schedule with the pediatric combined D, T, acellular Pertussis (aP), HB, inactivated poliovirus (IPV), Hib conjugate vaccine (DTaP-HB-IPV-Hib) and with the pneumococcal (Pc) conjugate vaccine containing 13-valent. Upon lymphodepletion preceding CAR T-cell infusion, MM pts (n = 24) had significantly lower sero-protection rates compared to NHL pts (n=68) against D: 4/23 (17%) vs. 30/60 (50%), T: 8/24 (33%) vs. 57/62 (92%), Hib: 2/24 (8%) vs. 29/61 (48%), VZV: 7/24 (29%) vs. 57/62 (92%), and Mv: 12/24 (50%) vs. 58/62 (94%). There was a trend toward lower HB sero-protection titers in MM pts [4/24 (17%)] compared to NHL pts [23/62 (37%)] (p=0.12). Similar immunization rates were found for HA (52% for both groups). At least 6 months after CAR T-cell infusion, the seroprotection rates of pts against D, T, Hib,VZV and Mv remained similar. In vaccinated pts, the median time from CAR-T cell infusion to first vaccine administration was 7 months (IQR, 6-11). Among pts who were not protected prior to vaccination, the response rates were as follows: 82% for D (14/17), 100% for T (4/4), 26% for Hib (6/23), 52% for HB (14/27), and 12% for pneumococcus (Pc) (3/26). The geometric mean titers (GMTs) increased significantly after revaccination against D (0.08 to 0.49; p =0.001), T (0.35 to 0.61; p =0.015), Pc (8.93 to 14.35; p =0.057), and HB (5.54 to 16.12; p =0.035), but not for Hib (0.30 to 0.81; p =0.104). Among immune factors, we found that pts with detectable circulating B lymphocytes CD20+ (cut off > 64 cells/mL) exhibited significantly higher antibody titers following the D and HB vaccines compared to pts with undetectable B cells (p <0.01 and p<0.01, respectively). Conclusion Pts treated with CAR T-cells retain immunity of prior vaccines. We observed lower sero-protection in MM pts treated by BCMA CAR T-cell compared to NHL pts treated with anti CD19 CAR T-cells, due to prior treatments targeting long-lived plasma cells. Immunization against D, T, Hib, and HB is effective in CAR-T cell recipients at least six months after infusion suggesting that memory B cells can be remobilized. These findings highlight the clinical relevance of implementing early and targeted revaccination strategies to restore protective immunity and prevent severe infections in CAR T-cell recipients.
Source: Blood
Authors: Stéphanie Cordeil, Anne Conrad, Violaine Safar, Remi Pescarmona, Yanis Merad, Emmanuelle Ferrant, Baptiste Jean, Camille Golfier, Lionel Karlin, Anne Lazareth, Zofia Gross, Dana Ghergus, Caroline Le Lan, Edith Julia, Estelle Bourbon, Helene Lequeu, Gabriel Antherieu, Emmanuel Bachy, Fabienne Venet, Herve Ghesquieres, Pierre Sesques, Florence Ader
Institution: Hospices Civils de Lyon
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417016197
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