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Open Forum Infectious Diseases ; 8(SUPPL 1):S777-S778, 2021.
Article in English | EMBASE | ID: covidwho-1746287


Background. Hematopoietic stem cell transplantation (HCT), and other forms of cellular therapies such as chimeric antigen receptor T cell therapy (CAR-T), while of critical therapeutic value, confers significant, long-term risk of infectious complications. Recipients would benefit from evaluation by infectious disease (ID) specialists. However, amidst many existing guidelines from ID and oncology societies, pre-transplant ID evaluation and management practices vary across US institutions. To better understand these variations and identify targets for standardization, we conducted a survey of ID and oncology providers at transplant centers in the US. Methods. A 38-question, anonymous, voluntary, online survey was distributed via Google Forms to a professional organization e-mail list of ID providers as well as to followers of relevant Twitter accounts. Responses were collected and analyzed. Results. A total of 51 responses were received, the majority of which (68.6%) came from ID providers. 60.8% of respondents worked at healthcare facilities with over 500 beds. 43 respondents (84.3%) reported that their center performed autologous and allogeneic HCT as well as CAR-T. 56.8% of CAR-T centers use a standardized template, compared to 70.8% of those providing HCT. For allogeneic HCT centers, 8% reported that no ID evaluation is offered;34% reported that it is offered "sometimes." Practices varied for treatment of latent tuberculosis infection prior to HCT: 26.5% treat "All the time;" 10.2% treat "Very rarely." In assessing risk factors, only 63% and 54% identified HIV infection and healthcare occupation, respectively, as epidemiologic risk factors for tuberculosis infection. 59.2% answered that < 10% of patients are screened for Strongyloides. Only 5 respondents reported universal Strongyloides screening prior to transplant. COVID-19 vaccination for family is recommended "Always" by 95.5% of respondents. 25% have offered influenza vaccination to family through the transplant clinic. Conclusion. Practices around pre-HCT infectious disease evaluation and management are heterogenous among the centers surveyed. The adoption of standardized screening for and management of infectious diseases in this patient population would likely be beneficial.

Blood ; 138:2537, 2021.
Article in English | EMBASE | ID: covidwho-1736299


It is well established that COVID-19 carries a higher risk of morbidity and mortality in patients (pts) with hematologic malignancies. Emerging data suggests that despite the 3 COVID-19 vaccines with emergency use authorization (EUA) by the FDA inducing high levels of immunity in the general population, pts with hematologic malignancies have lower rates of seroconversion for the SARS-CoV-2 Spike antibody (Spike IgG) and thus possibly lower protection against severe COVID-19. We established a program of rapid vaccination and evaluation of response in an inner city minority population to help determine the factors that contribute to the poor seroconversion to COVID-19 vaccination in pts with hematologic malignancies. We conducted a cross-sectional cohort study of pts with hematologic malignancies seen at Montefiore Medical Center between March 29, 2021 and July 8, 2021 who completed their vaccination series with 1 of the 3 FDA EUA COVID-19 vaccines, Moderna, Pfizer, or Johnson & Johnson (J&J). We qualitatively measured Spike IgG production in all pts using the AdviseDx Spike IgG assay and performed quantitative analysis on pts who completed their vaccination series with at least 14 days (d) after the 2 nd dose of the Moderna or Pfizer vaccines or 28d after the single J&J vaccine. Safety data was collected via questionnaires or as part of the electronic medical record. We analyzed the characteristics of these pts using standard descriptive statistics and associations between pts characteristics, cancer subtypes, treatments, and vaccine response using a Fisher Exact test, Kruskal-Wallis Rank Sum test, or Kendall Tau-b test. A total of 121 pts with hematologic malignancies were enrolled and another 10 pts were included by retrospective chart review. Five pts did not have a Spike IgG performed after consent and excluded. Ten patients had Spike IgG testing before completion of their vaccination series and excluded from quantitative analyses. A total of 116 pts were included in immunogenicity analysis and 106 pts in quantitative analysis. Baseline characteristics and representative malignancies are listed in Table 1. Seventy pts (60%) received Pfizer, 36 pts (31%) Moderna, and 10 pts (9%) J&J. Median time from vaccination completion to Spike IgG was 40d. We observed a high-rate of seropositivity (86%) with 16 pts (14%) having a negative Spike IgG. Percent positivity was not statistically significant between vaccine types (p=0.50). We observed significantly lower seroconversion rates in pts with Non-Hodgkin lymphoma (p=0.005) and pts who received: cytotoxic chemotherapy (p=0.002), IVIG (p=0.01), CAR-T cell therapy (p=0.00002), and CD20 monoclonal antibodies (Ab) (p=0.0000008) especially within 6 mo of Spike Ab evaluation (p=0.01). All pts who received anti-CD19 (Axi-cel) CAR-T therapy (0/6) were seronegative, and 1 pt that received BCMA directed CAR-T (Cilta-cel) was seropositive with no association between timing CAR-T cell infusion and seroconversion/titer. Use of BCL2 inhibitors (p=0.04), CD20 monoclonal Ab (p=0.0009), CAR-T cell therapy (p=0.01), BTK inhibitors (p=0.04), current steroid use (p=0.002), and IVIG (p=0.003) also correlated with significantly lower Ab titers with a trend toward lower Ab titers in pts on any active cancer therapy at time of vaccination (p=0.051). Immunomodulatory drugs (p=0.01) and proteasome inhibitors (p=0.01) had significantly higher seroconversion rates, and pts with history prior COVID-19 (12/106) had significantly higher Ab titers (p=0.0003). Of 47 pts who received stem cell transplant, 43 received an autologous (37 seropositive, 6 seronegative) and 4 an allogeneic transplant (3 seropositive, 1 seronegative), with no significant association with seroconversion, Ab titer, or time since transplant (greater or less than 1 year). The majority of pts, 64% and 53%, reported no adverse effects (AE) to the 1 st and 2 nd dose respectively. The most common AE were mild in severity and included sore arm, muscle aches, fatigue, and fever. No life-threatening AE were observed. Our findings indicate hat vaccination is safe, effective, and well tolerated in the majority of pts with hematologic malignancies. We observed that pts receiving B-cell depleting therapies are unable to mount an effective serological response to COVID-19 vaccines and remain vulnerable to the disease. Novel immunization strategies (active or passive) are urgently needed in this population. [Formula presented] Disclosures: Gritsman: iOnctura: Research Funding. Shastri: Onclive: Honoraria;Kymera Therapeutics: Research Funding;Guidepoint: Consultancy;GLC: Consultancy. Halmos: Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding;Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding;Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding;AbbVie: Research Funding;Boehringer-Ingelheim: Membership on an entity's Board of Directors or advisory committees, Research Funding;Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding;GSK: Research Funding;Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding;Mirati: Research Funding;Elevation: Research Funding;Blueprint: Research Funding;Advaxis: Research Funding;Eli-Lilly: Research Funding;TPT: Membership on an entity's Board of Directors or advisory committees;Apollomics: Membership on an entity's Board of Directors or advisory committees;Guardant Health: Membership on an entity's Board of Directors or advisory committees. Verma: BMS: Research Funding;GSK: Research Funding;Novartis: Consultancy;Stelexis: Consultancy, Current equity holder in publicly-traded company;Eli Lilly: Research Funding;Curis: Research Funding;Medpacto: Research Funding;Incyte: Research Funding;Acceleron: Consultancy;Stelexis: Current equity holder in publicly-traded company;Celgene: Consultancy;Throws Exception: Current equity holder in publicly-traded company.

Blood ; 136:10-11, 2020.
Article in English | EMBASE | ID: covidwho-1348311


Background: Adoptive immunotherapy using CD19-targeted Chimeric Antigen Receptor T-cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). We have demonstrated the efficacy of FDA-approved axicabtagene ciloleucel (Yescarta) in a multiethnic New York City underserved population with 80% complete response (CR) rate in the first ten patients treated at our institution (Abbasi et al., 2020). There is limited data on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy. Methods: We conducted a retrospective study of patients who received CAR-T therapy at our institution between 2018-2020. Variables collected include patient demographics, absolute neutrophil (ANC), lymphocyte (ALC) and monocyte counts (AMC) at Day 30, hematologic reconstitution (ANC≥ 1500/µL) at Day 90 (D90), presence or absence of infections after D30 by clinical and/or microbiological parameters. Associations between presence of infection and D30 ANC, ALC, AMC, ANC/ALC ratio, AMC/ALC ratio were assessed using Kruskal-Wallis test. Association between infection and hematologic reconstitution at D90 was done using Chi-square test. Kaplan-Meier curves with log-rank test were used to evaluate overall survival (OS) and progression-free survival (PFS). Results: Nineteen patients were evaluated in our study, consisting of 42% (8) Hispanic, 32% (6) Caucasian, 21% (4) African-American, and 5% (1) Asian subjects. Based on clinical and microbiologic data, 47% (9) developed an infection after D30 (infection group) while 53% (10) of subjects remained infection-free after D30 (non-infection group). The most common infection type observed was viral (11 patients) followed by bacterial (8 patients) and fungal (3 patients) (Table 1). Of 25 total infectious events, 44% (11) were grade 1 or 2 and 48% (12) were grade 3 with 10 being viral in etiology. Two deaths occurred due to an infectious process. Three patients tested SARS-CoV-2 positive and were hospitalized with COVID-19 pneumonia. Median OS and PFS has not been reached in either group. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median ALC (1000/µL vs 600/µL p=0.04), a lower median ANC/ALC ratio (1.4 vs 4.5 p<0.01) and a lower median AMC/ALC at D30 (0.36 vs 1.33, p=0.01) (Table 2). In addition, patients in the infection group had a lower rate of hematologic reconstitution (ANC >1500/µL) at D90. We observed that only 22% (2) of patients had recovered ANC > 1500/µLin the infection group as opposed to 80% (8) in the non-infection group at D90 (p= 0.038). Rates of cytokine release syndrome (CRS) were comparable between the two groups (55.6% vs 70% p=0.52). Surprisingly, rates of immune-effector cell associated neurotoxicity syndrome (ICANS) was lower (55.6%) in the infection group compared to (90%) non-infection group (p=0.09). Fourteen of 19 patients had follow-up over one year, of which 8 (57%) remained in complete remission (CR). Conclusions: We demonstrate an infection rate of 47% (9) beyond D30 in patients undergoing CD19 CAR-T. Increased ALC, lower ANC/ALC and AMC/ALC ratios at D30 may be predictive of infectious complications. Median OS has not been reached in our cohort. Given the potential clinical impact, our observations should be corroborated using larger datasets. [Formula presented] Disclosures: Steidl: Pieris Pharmaceuticals: Consultancy;Bayer Healthcare: Research Funding;Stelexis Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees;Ai eron Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Janakiram: ADC Therapeutics, FATE therapeutics, TAKEDA pharmaceuticals: Research Funding. Verma: BMS: Consultancy, Research Funding;acceleron: Consultancy, Honoraria;Janssen: Research Funding;stelexis: Current equity holder in private company;Medpacto: Research Funding.