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  • 1
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3465-3465
    Abstract: Introduction: Myeloid Derived Suppressive Cells (MDSC) constitute a heterogeneous population of immature myeloid cells characterized by their capacity to suppress innate and adaptive immune responses. As such, they have been proven, in solid tumors, to modulate malignancy by increasing tumor cell survival, angiogenesis, metastasis and tissue invasion. By contrast, reports on the role of MDSC in either acute myeloid (AML) or lymphoid (ALL) leukemias are very limited with unknown established impact on long-term outcomes. Patients and Methods: This monocentric prospective study included all adult patients eligible for first-line intensive chemotherapy for AML or ALL. The main objective was to investigate the presence of peripheral blood monocytic MDSC at diagnosis and after induction in such patients and to correlate their levels to complete remission (CR/CR with incomplete platelet recovery), cytologic relapse, leukemia-free (LFS) and overall (OS) survivals. Monocytic MDSCs were defined as CD15- CD34- CD16- CD14+ CD33+ CD11b+ DR-/low cells and assessed in a lysis-no-wash flow cytometry technique. Data acquisition was performed on a Navios® flow cytometer (Beckman Coulter, Miami, FL). MDSC were expressed as a percentage (%) of total nucleated cells defined as CD45+. MDSC% were compared to those of 21 healthy controls. The study was registered at the French Commission Nationale de l'Informatique et des Libertés as CNIL 2016-038. All patients gave informed consent. Analyses were performed in July 2021. Results: Between October 2017 and March 2021, 73 AML and 14 ALL were enrolled (Table 1). The median MDSC% in controls was 0.24% (range: 0.02-1.21). This % was significantly higher in AML compared to ALL (0.19% (range: 0-0.54) vs 0.14% (range: 0-0.35), p=0,01) and differed significantly from controls in ALL (p=0.0004) but not in AML (p=0.94). MDSC% after chemotherapy induction were available for 61 AML and 13 ALL at medians of 37,5 and 37 days, respectively. At that time, median MDSC% were similar between AML (0.84%, range: 0-28) and ALL (0.97%, range: 0-4.75) patients (p=0.52) but significantly higher than in controls for AML patients (p=0.001; ALL p=0.07). AML: MDSC% were not correlated to any other factors, especially ELN2017 classification (p=0.79). ROC curves for LFS established the threshold of 0,55% of MDSC at diagnosis as the best cut-off for analyses. MDSC% ( & lt; vs & gt;0,55%) was not predictive of CR/CRp (86.6% n=39/45 vs 78.5% n=22/28, p=0.56). However, 2-year LFS (67.7+8% vs 30.1+10%, p=0.005) and 2-year OS (71.5+8% vs 30.1+10%, p=0.001). (Figure 1) were significantly higher for patients with low MDSC% ( & lt;0.55%). The incidence of cytologic relapse after achieving CR/CRp was significantly lower in these low MDSC% patients (12.8% n=5/39 vs 45.4% n=10/22, p=0.01). The median percentage of MDSC increased significantly between diagnosis (0,19%) and post-induction (0,84%; p=0.001). Median post-induction MDSC% were similar between patients achieving CR/CRp (0.9%, n=53 evaluable) vs others (0.44%, n=8 evaluable, p=0.34). No impact on relapse incidence nor on LFS and OS was observed when comparing patients based on the median post-induction level of MDSC and ROC curves did not identify thresholds able to predict LFS or OS using MDSC% post-induction. Multivariate analysis confirmed the independent prognostic value of MDCS% at diagnosis for AML patients (LFS p=0.026, HR 3.6, 95%CI 1.88-6.91; OS p=0.02-, HR 2.6, 95%CI 1.11-5.95) together with ELN 2017 classification (LFS p=0.0001, HR 2.34, 95%CI 1.10-4.97; OS p=0.01, HR 2.57, 95%CI 1.18-4.11). ALL: MDSC% at diagnosis were not predictive of response as 13/14 patients achieved CR/CRp after induction. The percentage of MDSC increased significantly between diagnosis (0.14%) and post- induction (0.97%; p=0.002). Again, this had no consequence on relapse incidence in CR/CRp patients nor on LFS and OS when comparing patients based on median post induction MDSC%. Discussion: This study evidenced that a higher percentage of peripheral monocytic MDSC at diagnosis predict lower survivals in AML patients because of more relapse. This result has to be confirmed on larger cohorts as it may implicate to propose immune intervention before or in combination with chemotherapy to improve these patients' outcome. Indeed, these cells seem to be an independent biomarker and potentially promising targets for the development of novel therapeutic strategies. Figure 1 Figure 1. Disclosures Moreau: Sanofi: Honoraria; Amgen: Honoraria; Celgene BMS: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Oncopeptides: Honoraria.
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    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 2
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-09-21)
    Abstract: Graft-versus host disease (GVHD) remains one of the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (ASCT). Prophylactic T cell depletion via antithymocyte globulin (ATG) during ASCT conditioning is one of the standards of care for GVHD prophylaxis, although the optimal dosing strategy is still unclear. Recent studies have reported that absolute lymphocyte count at the time of ATG administration could predict survivals in ASCT from unrelated donors. Here this issue was examined in 116 patients receiving peripheral blood stem cells (PBSC) ASCT with purine analog/busulfan-based conditioning regimens between 2009 and 2019 in our department. The impact of lymphopenia at the time of ATG administration was evaluated in terms of overall survival, disease-free survival and GVHD-free/relapse-free survival. After a median follow-up of 4 years, no adverse effect of a profound lymphopenia was observed on patients’ outcome. Notably, a reduced dose of ATG in patients with profound lymphopenia did not translate into better survivals. This study indicates that ATG can be administered whatever the recipient’s lymphocyte counts in patients receiving a PBSC purine analog/busulfan-based conditioning regimen ASCT.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 3
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1812-1812
    Abstract: Introduction: The use of high-dose post-transplant cyclophosphamide (PTCY) has revolutionized graft-versus-host disease (GVHD) prophylaxis and allowed to successfully reconsider haplotransplant in recent years. As this strategy significantly reduces the incidence of both acute and chronic GVHD, PTCY has been thereafter considered not only in matched settings but also as sole GVHD prophylaxis, at least when considering myeloablative allotransplant using matched sibling (MSD) or unrelated (MUD) donors and bone marrow as source of graft. Here, PTCY, as a sole GVHD prophylaxis, was tested in a reduced-intensity conditioning (RIC) setting, using peripheral blood stem cells (PBSC) as source of graft considering that this platform is currently broadly used worldwide in adults. Methods: This prospective monocentric phase 2 study was designed with the main objective to demonstrate the feasibility and safety of using only PTCY (without cyclosporine A nor mycophenolate mofetyl after transplant) in adults (18-70 years old) eligible for a RIC PBSC transplant with MSD or MUD. The Baltimore platform with 2 days of PTCY 50mg/kg/day on days 3 and 4 post infusion was considered as conditioning regimen, using fludarabine for lymphoid disease or clofarabine for myeloid disease. The primary objective was to appreciate the incidence of corticosteroid-resistant acute grade 3-4 GVHD (CR 3-4 GVHD) within 100 days post-transplant. According to statistical rules, patients have to be included in a step by step fashion (3, 3, 6, 15, 15 and 17 patients) for a total of 59 evaluable patients (meaning having received PTCY), in order to stop the protocol soon enough in case of excessive rate of deleterious severe acute GVHD (graded according to Mount Sinai International Consortium). Thus, the trial had to be stopped in case of documentation of & gt; 2 CR 3-4 GVHD for the first 3 patients, & gt;3 CR 3-4 GVHD for the first 6 patients, & gt; 4 CR 3-4 GVHD for the first 12 patients, & gt; 6 3-4 CR GVHD for the first 27 patients, & gt; 8 CR 3-4 GVHD for the first 42 patients and finally as soon as & gt; 9 CR 3-4 GVHD for the last included patients. All patients gave informed consent. The trial was registered at ClinicalTrials.gov Identifier: NCT03263767. Results: The results of the first 27 first patients (males n=17 and female n=10; median age: 59 years old (yo), range: 26-70) are reported here. They were included between February 2018 and November 2020. Diagnoses were AML (N=8), MDS (N=5), CMML (N=2), myelofibrosis (N=5), CML (N=1), DLBCL (N=1), T-cell lymphoma (N=1), Philadelphia positive B-ALL (N=1), CLL (N=1), lymphoblastic lymphoma (N=1) and mixed phenotype acute leukemia (N=1). Donors were MSD in 10 cases and MUD in 17. Only one primary graft failure was documented in a 61 yo MDS patient with active disease at transplant. He is however still alive in response after autologous reconstitution. With a median follow-up of 17.6 months (range: 10-42) for alive patients at the time of analysis (July 2021), 1-year and 2-year survivals were 80.9+7% and 74.7+9%, respectively, for both OS et DFS. GVHD-free/relapse-free survival (GRFS) at 1-year and 2-year was 58.7+9% and 52.2+10%, respectively. Three relapses (11%) and 6 deaths occurred. Deaths were due to acute GVHD in 4 patients (including 1 with sepsis and 1 with SARS-COVID 19 infection) and relapse in 2. Grade 2, 3 and 4 acute GVHD occurred in 11, 1 and 4 patients, respectively, for a total of 59% of grade 2-4 acute GVHD. CR 3-4 GVHD was observed in all of 5 patients with acute grade 3-4 GVHD and 4 died related to GVHD. Moderate/severe chronic GVHD occurred in 5/22 (22.7%) evaluable patients, including 4 still on immunosuppressive therapy at 40, 28, 25 and 16 months post-transplant. Overall non-relapse mortality (NRM) was 14.8% and related to acute GVHD. However, the number of cases conducting to stop the protocol was not reached. Conclusion: PTCY as a sole GVHD prophylaxis is here demonstrated as possible and relatively safe for adults receiving a matched PBSC Baltimore-based RIC allograft. The very good survivals reported here may be related to a strong GVL effect associated with the high incidence of acute GVHD. However, because of this high incidence and the fact that NRM was related to GVHD after this first analysis, we have now made an amendment to test the addition to PTCY of one day of anti-thymoglobulin (ATG) 2.5 mg/kg on day-2 for the next 32 patients to be included. This second cohort receiving PTCY+ATG as a sole prophylaxis is ongoing. Disclosures Moreau: Celgene BMS: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Oncopeptides: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 4
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1985-1985
    Abstract: Introduction: Prophylactic T cell depletion with antithymocyte globulin (ATG) remains a standard of care for GVHD prophylaxis during allotransplant (ASCT). Although the optimal ATG dosing strategy is still unknown, recent studies have reported that recipient absolute lymphocyte counts (ALC) at the time of ATG administration may predict survivals in ASCT with unrelated donors, suggesting that the dose (especially at the cut off of 〈 0.1x109/L) and timing of ATG administration must be taken into account (Soiffer et al, JCO 2017; Kennedy et al, BBMT 2018). Our experience on the impact of lymphopenia at the time of ATG administration during allotransplant is reported here. Materials & Methods: All adults transplanted in our department between 01/2009 and 03/2019 with a Purine analogue/Busulfan/ATG based conditioning regimen and PBSC as source of graft from a matched or 9/10 mismatched donor were eligible. Reduced-intensity conditioning (RIC) regimen consisted of fludarabine 30mg/m²/day (d) from d-6 to d-2, busulfan 3,4 mg/kg/d from d-4 to d-3 and ATG (Thymoglobuline, Sanofi, Lyon, France) 2,5 mg/Kg/d, d-2 and d-1 (FB2A2) or the same but with clofarabine 30mg/m²/d in replacement of fludarabine with 1 or 2 d of ATG (CloB2A2/CloB2A1). Reduced-toxicity myeloablative conditioning regimens (RT-MAC) consisted of the same as FB2A2 but with 3 or 4 d of busulfan instead of 2 (FB3A2/FB4A2). All grafts were administered freshly on the day of the collection while patients (pts) had already received ATG. GVHD prophylaxis was ciclosporine alone for pts with a sibling donor while pts grafted with a matched (MUD) or a 9/10 mismatch (mmUD) unrelated donor received ciclosporine+MMF. We exhaustively looked at pts for whom a blood differential was available at the time of ATG administration in order to study the impact on OS, DFS and GRFS (no grade 3-4 acute GVHD, no moderate/severe chronic GVHD and no relapse) of a profound lymphopenia vs not. Results: Of 395 eligible pts, 116 (median follow-up for alive pts: 49 months) were documented with a differential at time of ATG administration, confirming that this analysis is not a routine practice in our department and probably in many centers. RIC was administered in 80 (69%) of the pts including 39 FB2A2, 12 CLOB2A2 and 29 CLOB2A1. RT-MAC was administered in 36 (31%) pts, including 27 FB3A2 and 9 FB4A2. Seventy-six pts had a myeloid disease while 40 had a lymphoid disease. Donor types were siblings (n=33), MUD (n=70) or 9/10 mmUD (n=13). For the entire cohort, 4y OS, DFS and GRFS were 56.2% (47-66), 40.9% (32-51) and 34.5% (26-45), respectively. No difference in survivals was observed between lymphoid vs myeloid pts, pts transplanted with sibling vs other donors, pts receiving a RIC vs a MAC or a CloB2 vs a FB2 RIC regimen. Median ALC at time of start of conditioning was .915x109/L (range: .010-15.780). No difference in terms of survivals was observed when considering pts under this threshold vs others. ROC curve analysis failed to identify a cut-off allowing to predict better survivals according to ALC at the time of ATG administration (ALC/ATG). Median ALC/ATG was .070x109/L (range: 0-2.300). No difference in terms of survivals was observed when considering pts under this threshold vs others. The same was true when considering .100x109/L as ALC/ATG cut-off. Regarding MAC, the median ALC/ATG was .100x109/L with no difference in survivals between pts under or above this value. The same was true for RIC with ALC/ATG cut-offs 〈 median (.055x109/L) or 〈 .100 x109/L. Interestingly, considering pts with ALC/ATG 〈 .100 x109/L within the RIC setting, survivals were similar between those who received 1d (n=25) vs 2d (n=28) of ATG. This analysis was not performed for pts with ALC/ATG 〉 .100 x109/L as only 4 of them received 1d of ATG vs 23 2d. The dose of CD34+ and CD3+ T cells infused had no impact also on survivals. Conclusion: This study demonstrates that profound lymphopenia at the time of ATG administration as part of a RIC as well as a RT-MAC Purine analogue/Busulfan/ATG based conditioning regimen has no impact on outcomes. Moreover, a reduced dose of ATG in RIC pts with profound lymphopenia at the time of ATG administration did not translate into better survivals. Other unknown factors rather than recipient lymphopenia remain to be discovered to optimize individualized dosing of ATG. Disclosures Peterlin: AbbVie Inc: Consultancy; Astellas: Consultancy; Jazz Pharma: Consultancy; Daiichi-Sankyo: Consultancy. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Le Gouill:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Roche-Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support. Chevallier:Daiichi Sankyo: Honoraria; Incyte: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 5
    In: Annals of Hematology, Springer Science and Business Media LLC, Vol. 98, No. 6 ( 2019-6), p. 1441-1447
    Type of Medium: Online Resource
    ISSN: 0939-5555 , 1432-0584
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
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  • 6
    In: Cancer Medicine, Wiley, Vol. 10, No. 20 ( 2021-10), p. 7194-7202
    Abstract: Three different scoring systems have been developed to assess pre‐transplant comorbidity in allogeneic hematopoietic stem cell transplantation (Allo‐HSCT): the Hematopoietic Cell Transplantation‐Specific Comorbidity Index, the Comorbidity/Age index, and the Augmented Comorbidity/Age index. All were devised to predict overall survival (OS) and disease‐free survival (DFS) survivals and non‐relapse mortality (NRM) in patients receiving HLA‐matched Allo‐HSCT, but their performance has scarcely been studied in the haploidentical Allo‐HSCT setting with post‐transplant cyclophosphamide, a procedure in constant expansion worldwide. Methods To address this issue, their impact on survivals and NRM was examined in a cohort of 223 patients treated with haploidentical Allo‐HSCT in four different centers. Results With a median follow‐up of 35.6 months, 3‐year OS, DFS, and NRM were 48.1% ± 4%, 46.3% ± 4%, and 30.0% ± 3%, respectively. No impact was found for any of the three comorbidity scores in univariate analysis. In multivariate analyses, the only three factors associated with lower OS were DRI ( p   〈  0.001), an older age of recipients (≥55 years old, p  = 0.02) and of donors (≥40 years old, p  = 0.005). Older donor age was also associated with lower DFS and higher NRM. Conclusion The comorbidity scores do not predict survivals nor NRM in haploidentical Allo‐HSCT with PTCY, suggesting that pre‐transplant comorbidities should not be a contra‐indication to this procedure.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
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    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 7
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4914-4914
    Abstract: Introduction: Allogeneic stem cell transplantation (allo-SCT) remains the only curative option for patients with myelodysplastic syndrome (MDS). If recent data have shown encouraging results with haploidentical (haplo) donors in this context, no comparison with allo-SCT using other source of graft (matched sibling [MSD] or unrelated [MUD] donors) has been reported so far. Methods: We retrospectively considered 102 consecutive adults transplanted for MDS between March 2010 and August 2020 in our Department, comparing outcomes between those receiving a graft from a MSD, a MUD or a haplo-donor. Results : Thirty-three, 48 and 21 patients respectively received a graft from a MSD, MUD or haplo donor. Peripheral blood stem cells (PBSC) were the source of graft for all patients. The median age of the whole cohort was 63 years old (range: 20-74) and the median follow-up was 23 months (range: 0-125). The three groups shared similar characteristics (gender, type of MDS, disease status, disease risk index, CMV status, ABO compatibility, peripheral blood stem cells graft count, conditioning regimen) except median recipient age which was younger in matched patients ( 61 vs 65 MUD vs 65 Haplo, p=0,04) and median donor age which was older in matched transplant ( 61 vs 34 MUD vs 42 Haplo, p & lt; 0,001) (Table 1). With a median follow-up of 46,4 months, the 4-year OS (Figure 1) was comparable between the three groups (haplo: 60.1 % ± 11,0 % , MSD: 59,0 % ±9,4 % and MUD: 61.2 % ± 7,2 %, p = 0.88) as well as the 4-year DFS (Figure 2) (55.9 % ± 11,1 % vs 51,2 % ±9,2 % vs 59.6 % ± 7,2 %, p = 0.78) and the cumulative incidence (CI) of NRM (34.6 % ±12,4 % , 15,4% ± 6,4% and 23.8 % ± 6,4 %, p = 0.21). Also, the 4-year CI of acute grade 3-4 GVHD (14,3% vs 15,2% vs 20,8%, p=0.79) and of moderate/severe chronic GVHD (14,3% vs 24.2% vs 27,1%, p=0.56) were not significantly different. The 4-year GRFS seemed better with haplo (Figure 3) but this was not statistically significant (56,1 % ± 11,0% vs 28,1% ±9,2 % vs 32,8 % ± 7,4%,p=0 .41). Conclusions: These data suggest that haplo-identical donors represent a valid alternative in MDS patients lacking a MSD or a MUD for allo-SCT. Figure 1 Figure 1. Disclosures Moreau: Oncopeptides: Honoraria; Amgen: Honoraria; Celgene BMS: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 8
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 254-254
    Abstract: Introduction: Data regarding the efficacy of anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) messenger RNA vaccines in immunocompromised hosts are scarce and no data yet appear to be available for patients with hematological malignancies who also received chimeric antigen receptor-T (CAR-T) cells therapy. Methods: The efficacy and safety of one and/or two injections of the BNT162b2 (Pfizer-BioNTech) vaccine was evaluated retrospectively in 23 CAR-T recipients in our Hematology Department, compared to a cohort of 25 healthy caregivers, vaccinated concomitantly between January 28 and May 31, 2021. None of these individuals had a previous clinical history of COVID-19. Results: Overall, the patients (14 males and 9 females) had a median age of 62 years old (range: 21-79) and had received CAR-T for high-grade lymphoma (n= 20) or acute lymphoblastic leukemia (n= 3). Eight and 3 had been respectively previously autografted or allografted and two were allografted after CAR-T. All patients were pretreated for lymphodepletion by fludarabine + cyclophosphamide before CAR-T infusion. The CAR-T provided were axicabtagene ciloleucel (Yescarta, Kite/Gilead, n=16, tisagenlecleucel (Kymriah, Novartis Pharma, n=5 and brexucabtagene autoleucel (KTE-X19, Tecartus, Kite/Gilead, n=1). One additional patient received allogeneic UCART19 (Servier). The median delay between CAR-T administration and the first vaccine (V1) was 401 days (d; range: 113-819). All patients but 2 were in complete remission at V1 and 3 were still on therapy (revlimid n=1, tafasitamab n=1, chemotherapy n=1). After V1, antibody response to the SARS-CoV-2 spike protein receptor-binding domain was tested by the Roche Elecsys® assay at a median time of 29 d (range: 16-32) in 19 patients and 23 d (range:18-32) in controls. At that time, only 4/23 patients (21%) but all controls (100%) had a positive anti-spike antibody response (p & lt;0.001). Among seropositive cases, median IgG titers were higher in controls (35.1 U/mL, range 2.2- & gt;250) than in patients (5.9 U/mL range 4.1-41.6, p=0.06). The highest IgG titer ( & gt;250) was obtained in 2 controls. The median delay between V1 and the second vaccine (V2) was 28 d (range: 14-46) for patients and 23 d (range: 18-32) for controls. Among the 20 patients tested after V2, 17 had also been tested after V1 while 3 were tested only after V2. All controls were tested after V2. The second serology assay was performed at a median interval from V2 of 52 d (range: 21-99) for patients and 58 d (range: 32-71) for controls. This serology assay was positive in 6 patients (30%), while all controls (100%, p & lt;0.001) had again a positive response. Three out of these 6 patients (15% of all patients) achieved the highest IgG titer according to the serology assay used. Among the 4 patients with positive antibody titers after V1, 3 remained positive including one reaching the highest IgG titer. The fourth patient has not yet received V2. Median IgG titers could not be compared with controls because various methods of detection were used after V2. However, all controls tested again by Roche Elecsys® displayed the highest IgG titer ( & gt;250) after V2. The two patients in relapse and treated by chemotherapy or tafasitamab did not develop antibodies after V2 conversely to the patient under maintenance by revlimid. The delay between CAR-T infusion and vaccine did not influence the antibody response nor did the rate of lymphopenia as almost all patients remained under a lymphocyte threshold of 1x10 9/L. Finally, with a median follow up from V1 of 77 d (range: 49-127) in patients and 81 d (range: 62-95) in controls, no COVID-19 infection has been documented in any of these participants. Conclusion: This study shows that the administration of two doses of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine provides a low rate of seroconversion (30%) in recipients of CAR-T therapy. This is likely related to the profound B-cell depletion induced by this treatment precisely targeting CD19+ cells. Investigation of the development of specific T-cell responses in these individuals could provide more information about the efficacy of vaccination in this context. Disclosures Moreau: Celgene BMS: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; Oncopeptides: Honoraria.
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    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 9
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3908-3908
    Abstract: Introduction In a previous observational study of 117 allogeneic hematopoietic stem cell transplant (Allo-HSCT) recipients, we found that 83 % of them achieved a specific humoral response after two doses (V1 and V2) of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine (Pfizer BioNTech). However, although 61.5% of the patients achieved the highest detectable IgG titers, this proportion remained significantly lower than what was observed in healthy controls, where 100% reached these highest antibody titers. Here, we investigated whether a third dose of vaccine would improve the anti- SARS-CoV-2 response in Allo-HSCT recipients. Methods This monocentric retrospective study aimed at evaluating the efficacy of a third vaccine (V3) of BNT162b2 in a cohort of Allo-HSCT adult recipients. Patients with previous clinical or asymptomatic biological COVID-19 infection at V1 were excluded from the study. A cohort of healthy volunteers (caregivers from the Clinical Hematology Department) who had also already received V1 and V2 was considered as controls. All participants were vaccinated between January 20 and June 1, 2021. Analyses were performed in July 2021. Antibody response to the SARS-CoV-2 spike protein receptor-binding domain was tested after V2 for all subjects (Serology post V2, SpV2) using the Roche Elecsys® assay. All subjects benefited later from another evaluation of specific serum antibodies as monitoring (Serology post V2+, SpV2+) or after V3 (Serology post V3, SpV3). Various serological methods were used for these later assays because performed outside of our hospital for some patients. Considering thresholds of negativity and positivity as well as highest values for each test, we were able nevertheless to distinguish 4 sub-groups: i) negativity at both SpV2 & SpV2+/SpV3, ii) increase of the IgG titer between SpV2 & SpV2+/SpV3, including patients showing seroconversion, iii) decreased or stable IgG titer between SpV2 & SpV2+/SpV3 and iv) highest IgG titers at both SpV2 and SpV2+/SpV3. Results A cohort of 25 controls and 114 patients, including 91 who received V3 (V3+) and 23 who did not (V3-) was considered for the purpose of this study. The characteristics of participants and delays from SpV2 to SpV2+ or SpV2 to SpV3 are reported in Tables 1 and 2. The serological methods used for the latest assays are reported in Table 2 with criteria of negativity, positivity and highest IgG titer values. V3- patients were younger, with less myeloid disease than V3+ cases and had not received myeloablative conditioning. However, both V3+ and V3- groups shared similar median intervals between Allo-HSCT and V1, incidence of previous graft versus host disease (GVHD), proportions of patients under chemotherapy or immunosuppressive drugs and median lymphocyte counts at V1, suggesting similar immune status. The reasons for not receiving V3 were forgetting, refusal or surveillance after detection of the highest IgG titer at SV2. Samples from controls, all evaluated by Roche Elecsys®, showed the highest anti-spike antibody value ( & gt;250U/mL) at both SpV2 and SpV2+, suggesting a persistent response without the need of a third vaccine in this healthy population. The proportion of patients still negative at SpV2+/SpV3 was similar between V3- and V3+ patients (17% vs 12%, p=0.74). However, the proportion of patients showing a decreased/stable IgG titer between SpV2 and SpV2+/SpV3 was significantly higher for V3- cases (35% vs 4%, p=0.0001) (Table 2). Moreover, the proportion of patients with the highest IgG titer at SpV2+/SpV3 was significantly higher in the V3+ sub-group (80% vs 43%, p=0.001), even if it remained significantly lower than in controls (p=0.03). The proportion of patients showing an IgG titer increase between SpV2 and SpV2+/SpV3 was higher in V3+ vs V3- patients (24% vs 4%, p=0.06). The difference was not significant as surprisingly one V3- case showed a seroconversion without any argument for SARS-CoV-2 infection between SpV2 and SpV2+. Three patients out of 14 (21%), with a negative SpV2, showed a seroconversion after V3. Finally, with a median follow up from V1 of 106 days in V3+ patients, 138 days in V3- patients and 154 days in controls, no COVID-19 infection was documented in any participant. Conclusion This study shows the interest of a third dose of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine after allograft as more patients are documented with less decrease of IgG titers and the highest IgG values after V3. Figure 1 Figure 1. Disclosures Moreau: Abbvie: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Celgene BMS: Honoraria; Oncopeptides: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Transplantation and Cellular Therapy, Elsevier BV, Vol. 28, No. 5 ( 2022-05), p. 279.e1-279.e4
    Type of Medium: Online Resource
    ISSN: 2666-6367
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 3056525-X
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