ALBERT

Description: Introduction: A number of treatment (Tx) options are available for ND AML pts including high-intensity (HI) chemotherapy ("7+3" regimen) followed by consolidation chemotherapy or allogeneic hematopoietic cell transplantation, low/intermediate-intensity (LI) therapies (low-dose cytarabine or hypomethylating agents), best supportive care (BSC), or no Tx. While data describing HCRU by AML pts informs health systems, clinicians, and pts of the requirements for managing AML pts, HCRU studies in this population are lacking. An analysis of ND AML pts from the Connect® MDS/AML Disease Registry was conducted to examine HCRU in pts receiving different Tx modalities. Methods: The Connect MDS/AML Disease Registry (NCT01688011) is an ongoing, prospective observational cohort study of pts in the USA with ND AML (aged ≥ 55) or myelodysplastic syndromes (aged ≥ 18). All interventions are conducted in accordance with physicians' standard of care. Pt demographics, disease characteristics, and Tx information were collected at screening and every 3 months from AML pts enrolled from December 2013 to March 2018. HCRU was assessed in ND AML pts according to Tx groups defined as HI, LI, BSC, or no Tx initiated ≤ 45 days post-diagnosis. Unplanned hospitalizations related to disease or Tx-related complications were assessed in all pts at 3 and 6 months post-enrollment. Response to Tx was analyzed in pts receiving HI and LI therapy only. Number of transfusion episodes (red blood cell or platelet) was calculated over 6 months post-enrollment, and at each month in pts receiving HI or LI therapy; data for partial months were excluded to accurately assess transfusion episodes/month. Results: A total of 434 AML pts, treated at 20 academic and 85 community/government centers, were included in the analysis. Median age was 70 years (range 55-92), 65% were male, and 83% were white. 95 (21.9%) pts received BSC/no Tx, 153 (35.3%) received LI therapy and 186 (42.9%) received HI therapy. A higher proportion of pts receiving HI therapy had ≥ 1 hospitalization compared with LI and BSC/no Tx groups (59.7% vs 49.0% vs 24.2%; P 〈 0.05). Mean number of hospitalization days/month in the HI, LI, and BSC/no Tx groups was 6.8 vs 5.7 vs 3.2 days, respectively. During the first 3 months of Tx, pts in the HI group spent a mean of 20.5 days in hospital vs 11.4 days for pts in the LI group, and 9.5 days for pts receiving BSC/no Tx. During the last 3 months of the study period, the number of hospitalization days decreased across all Tx groups to 10.4, 7.0, and 7.7 days, respectively. There were significant differences in mean monthly transfusion burden over the first 6 months of the study for pts in the HI and LI groups (4.9 vs 2.7 transfusion episodes/month; P 〈 0.01). During month 1 post-enrollment, the mean number of transfusion episodes in the HI group was 8.3 vs 3.4 in those receiving LI therapy (P 〈 0.01 after adjusting for insurance status). Over the 6-month study period, the transfusion rate decreased in both groups with a mean decrease of 6.3 and 1.8 transfusion episodes from month 1 to month 6 for HI and LI therapy, respectively (P 〈 0.01). At month 4, the transfusion rate in pts receiving HI therapy fell below that of the LI group (Figure), coinciding with the end or near completion of consolidation chemotherapy in the HI group. In logistic regression analyses, pts receiving HI therapy were significantly more likely to achieve complete remission (CR) vs pts receiving LI therapy, after adjusting for age, comorbidities, and disease risk (odds ratio = 4.2, 95% confidence interval 1.7-9.1; P 〈 0.01). Results from a sensitivity analysis, which excluded pts who had received a transplant, were consistent with the main analysis. Mortality rates were not significantly different between LI and HI groups at day 30 and day 60 but were at day 180 (P 〈 0.01; Table). Conclusions: These findings from the Connect MDS/AML Disease Registry highlight the level of HCRU in ND AML pts treated with different intensity therapies. While HCRU, as measured by transfusion burden and unplanned hospitalizations, was highest in the HI group, pts in the HI group were significantly more likely to achieve CR, and had lower mortality rates at a 180-day landmark. Higher HCRU rates during early Tx in the HI group are likely a reflection of cytopenia-related complications due to the highly myelosuppressive nature of HI regimens. Therefore higher HCRU during early therapy in the HI group may be offset by improved pt outcomes. Disclosures Abedi: BMS: Speakers Bureau; CIRM: Research Funding; Amgen: Research Funding; Celgene: Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Speakers Bureau. Erba:Astellas: Research Funding; Janssen: Research Funding; Janssen: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Amgen: Research Funding; Pfizer: Consultancy, Other: grant; Novartis: Consultancy, Speakers Bureau; Amgen: Research Funding; Novartis: Consultancy, Speakers Bureau; Astellas: Research Funding; Celgene: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas: Research Funding; Janssen: Research Funding; Celgene: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Amgen: Research Funding; Immunogen: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; Janssen: Research Funding; Amgen: Research Funding; Jazz: Consultancy, Speakers Bureau; Immunogen: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Astellas: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Pfizer: Consultancy, Other: grant; Daiichi Sankyo: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Pfizer: Consultancy, Other: grant; Takeda/Millenium: Research Funding; MacroGenics: Consultancy; Pfizer: Consultancy, Other: grant; MacroGenics: Consultancy; Juno: Research Funding; Juno: Research Funding; Seattle Genetics: Consultancy, Research Funding; Agios: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Incyte: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Immunogen: Consultancy, Research Funding; MacroGenics: Consultancy; Jazz: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; MacroGenics: Consultancy; Immunogen: Consultancy, Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Juno: Research Funding; Celgene: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Juno: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Agios: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Agios: Consultancy, Speakers Bureau. Pollyea:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celyad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy; Curis: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Roboz:Novartis: Consultancy; Aphivena Therapeutics: Consultancy; Argenx: Consultancy; Celgene Corporation: Consultancy; Roche/Genentech: Consultancy; Eisai: Consultancy; Astex Pharmaceuticals: Consultancy; Pfizer: Consultancy; Janssen Pharmaceuticals: Consultancy; Otsuka: Consultancy; Sandoz: Consultancy; Daiichi Sankyo: Consultancy; Janssen Pharmaceuticals: Consultancy; Orsenix: Consultancy; AbbVie: Consultancy; Eisai: Consultancy; Cellectis: Research Funding; Astex Pharmaceuticals: Consultancy; Argenx: Consultancy; Sandoz: Consultancy; Roche/Genentech: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; AbbVie: Consultancy; Jazz Pharmaceuticals: Consultancy; Celltrion: Consultancy; Aphivena Therapeutics: Consultancy; Celgene Corporation: Consultancy; Daiichi Sankyo: Consultancy; Celltrion: Consultancy; Jazz Pharmaceuticals: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; Bayer: Consultancy; Cellectis: Research Funding. Louis:Celgene: Employment; Cellmedica: Patents & Royalties. Flick:Celgene: Employment. Nifenecker:Celgene: Employment. Kiselev:Celgene: Employment, Equity Ownership. Swern:Celgene: Employment, Equity Ownership. Cogle:Celgene: Other: Steering Committee Member of Connect MDS/AML Registry.

Description: Introduction: In prior studies, only 13-22% of lower-risk (LR) MDS pts and 11-69% of higher-risk (HR) MDS pts received potentially disease-modifying therapy despite the proven benefits of reduced blood transfusions and prolonged survival. Pt age, frailty, and comorbidities are commonly assumed to influence therapy choice; however, this has not been proven and other factors may govern treatment (tx) decisions. To identify factors associated with receiving first-line tx for MDS, health services data from the Connect® MDS/AML Registry, which includes MDS pts treated in US academic, community, and government-based centers, were analyzed. Methods: The Connect MDS/AML Registry (NCT01688011) is an ongoing, prospective observational cohort study of pts with newly diagnosed acute myeloid leukemia (AML) (aged ≥ 55 years) or MDS (aged ≥ 18 years). Local AML and MDS diagnoses are confirmed by an independent central review of all available diagnostic reports. Baseline demographics, disease characteristics, laboratory parameters, and ZIP-code-level per capita income were collected at enrollment on MDS pts from December 2013 to March 2018. Analyses were performed separately for LR-MDS pts, defined as having Low- or Intermediate (Int)-1-risk MDS according to the International Prognostic Scoring System (IPSS), and HR-MDS pts, defined as having Int-2- or High-risk MDS. Uni- and multivariable logistic regression analyses were used to identify factors associated with early use of first-line tx in MDS pts, defined as chemotherapy or biotherapy initiated ≤ 45 days after diagnosis. Univariable testing was performed for each potential predictor; those with an association of P 〈 0.15 were included in multivariable analysis. The final multivariable model was derived using a score-based selection method. Pts receiving first-line tx (regardless of intensity) were compared with a combined group of pts receiving best supportive care (BSC) or no tx. Results: As of March 8, 2018, data from 536 MDS pts (232 HR-MDS and 304 LR-MDS) from 130 institutions (20 academic and 110 community/government) were available for analysis. In the LR-MDS group, median age was 76 years (range 28-95), with 65% male, and 89% white; 19% had private insurance, and the average median ZIP-code-level per capita income was $28,000 ($10,000-$92,000). In the HR-MDS group, median age was 73 years (range 19-94), with 67% male and 86% white; 23% had private insurance, and the average median ZIP-code-level per capita income was $26,000 (range $14,000-$83,000). In LR-MDS pts, univariable predictors of early first-line therapy initiation included baseline transfusion dependency (defined as ≥ 1 transfusion episode in the 8 weeks prior to diagnosis), comorbidities (higher Adult Comorbidity Evaluation 27 [ACE-27] score), having fluorescence in situ hybridization (FISH) or molecular analyses performed, Int-1 IPSS risk score, primary vs secondary MDS, and higher bone marrow (BM) blast percentage. Multivariable logistic regression analysis identified transfusion dependency (P = 0.001), Int-1 IPSS risk score (P = 0.026), BM blast percentage ≥ 5% (P = 0.002), and having both FISH and molecular genetic testing performed at diagnosis (P = 0.022) as factors significantly associated with early initiation of first-line tx (Table 1). Univariable analysis of HR-MDS pts showed insurance status, comorbidities (ACE-27 score ≤ 2), High IPSS risk score, primary vs secondary MDS, having flow cytometry analysis performed, lower baseline frailty, and BM blast percentage as univariable correlates associated with early tx. Multivariable logistic regression analysis identified private insurance coverage (P = 0.031) and BM blast percentage ≥ 10% (P = 0.021) as factors significantly associated with early initiation of first-line tx (Table 2). Conclusions: Early first-line tx in MDS pts was significantly associated with disease severity as indicated by transfusion dependency, higher IPSS risk score, and higher BM blast percentage. However, counter to common assumptions, age, frailty, and comorbidities were not associated with receiving early tx in MDS. Access to care may be an important factor in the tx of MDS pts, as having private health insurance and undergoing genetic testing were also significantly associated with receiving early tx. Additional pt-centered research with prescribing MDS physicians as stakeholders is needed to verify and extend these findings. Disclosures Cogle: Celgene: Other: Steering Committee Member of Connect MDS/AML Registry. Grinblatt:Celgene: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau; AbbVie: Consultancy. Komrokji:Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding. Savona:Boehringer Ingelheim: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding. Scott:Celgene: Consultancy, Honoraria, Research Funding. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Louis:Cellmedica: Patents & Royalties; Celgene: Employment. Flick:Celgene: Employment. Nifenecker:Celgene: Employment. Kiselev:Celgene: Employment, Equity Ownership. Swern:Celgene: Employment, Equity Ownership. Steensma:Takeda: Consultancy; Syros: Research Funding; Otsuka: Membership on an entity's Board of Directors or advisory committees; Onconova: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Janssen: Consultancy, Research Funding; H3 Biosciences: Research Funding; Celgene: Research Funding; Amphivena: Membership on an entity's Board of Directors or advisory committees; Acceleron: Consultancy.

Description: As immune-based therapies for cancer become potent, more effective, and more widely available, optimal management of their unique toxicities becomes increasingly important. Cytokine release syndrome (CRS) is a potentially life-threatening toxicity that has been observed following administration of natural and bispecific antibodies and, more recently, following adoptive T-cell therapies for cancer. CRS is associated with elevated circulating levels of several cytokines including interleukin (IL)-6 and interferon γ, and uncontrolled studies demonstrate that immunosuppression using tocilizumab, an anti-IL-6 receptor antibody, with or without corticosteroids, can reverse the syndrome. However, because early and aggressive immunosuppression could limit the efficacy of the immunotherapy, current approaches seek to limit administration of immunosuppressive therapy to patients at risk for life-threatening consequences of the syndrome. This report presents a novel system to grade the severity of CRS in individual patients and a treatment algorithm for management of CRS based on severity. The goal of our approach is to maximize the chance for therapeutic benefit from the immunotherapy while minimizing the risk for life threatening complications of CRS.

Description: Background: Diagnosing and risk stratifying MDS requires an integrated approach including morphologic, cytogenetic, and molecular genetic assessments to inform treatment decisions and aid prognostication. The WHO classification criteria for diagnosis of MDS were updated in 2016 (Arber DA, et al. Blood. 2016;127:2391-405) with specific recommendations; however, the impact of these updates on clinical practice patterns is unclear. We investigated testing patterns for pts with ND MDS treated in predominantly community- and government-based centers in the Connect® MDS/AML Registry and compared these practices with the WHO 2016 criteria. Methods: The Connect® MDS/AML Disease Registry (NCT01688011) is a large, US, multicenter, prospective observational cohort study of pts with ND acute myeloid leukemia (AML; aged ≥ 55 years) or MDS (aged ≥ 18 years). Baseline demographics, disease characteristics, and laboratory testing parameters were collected on MDS pts at enrollment to the Registry from December 2013 to March 2019. Pts were classified according to the International Prognostic Scoring System (IPSS) as having lower-risk MDS (LR-MDS; IPSS Low- or Intermediate-1-risk MDS) or higher-risk MDS (HR-MDS; IPSS Intermediate-2- or High-risk MDS). Differences in testing rates at enrollment between LR- and HR-MDS pts were assessed using a chi-square test with P 〈 0.05 considered statistically significant. Concordance with the recommendations of the WHO 2016 criteria, including frequency of SF3B1 testing, was assessed. Results: As of March 8, 2019, 694 pts with MDS were enrolled in the Registry; 392 (56.5%) with LR-MDS and 302 (43.5%) with HR-MDS. Median age was 75.0 vs 73.0 years, 66.3% vs 64.9% were male, and 70.6% vs 75.6% were insured by Medicare/Medicaid. There was a significant difference in bone marrow blast enumeration method between LR- and HR-MDS pts; the most common method was manual differential (75.9% vs 72.1%), followed by immunohistochemistry (IHC) (11.5% vs 21.5%) (P = 0.002). The mean (standard deviation) number of cells counted on manual differential was 361.7 (151.3) in LR-MDS pts and 348.2 (163.6) in HR-MDS pts. This was not significantly different between pt groups, but was below the recommended 500 cells. Presence of ring sideroblasts (RS) was more common in LR- than HR-MDS pts (39.8% vs 34.1%; P = 0.02); median percentage of RS was also higher in LR- than HR-MDS pts (25.0% vs 7.5%; P 〈 0.0001). The majority of pts underwent complete cytogenetic analysis at baseline; 97.4% of LR- and 95.7% of HR-MDS pts. Flow cytometry testing to assess cell lineage was widely done; 97.0% of HR-MDS pts and 93.6% of LR-MDS pts. To assess changes in diagnostic testing patterns following publication of the WHO 2016 criteria, LR- and HR-MDS pts were grouped based on their date of enrollment: pts enrolled prior to January 1, 2017, and pts enrolled from January 1, 2017 onward. Molecular testing rates increased in pts enrolled after January 1, 2017, from testing rates seen prior to 2017, in LR- and HR-MDS pts; however, testing rates remained 〈 40% (Table). Testing rates for specific mutations were higher in pts enrolled after January 1, 2017 than in those enrolled prior to 2017. In parallel with overall testing rates, testing rates for SF3B1 were also higher in pts enrolled after January 1, 2017; however, they remained at approximately 50% in these pts. During this time, rates of fluorescence in situ hybridization testing decreased by 36.1% and 26.0% in HR- and LR-MDS pts, respectively. Conclusions: In this analysis from the Connect® MDS/AML Registry, increased SF3B1 testing rates were observed following the publication of the WHO 2016 criteria, suggesting uptake of this recommendation by physicians. The increase in testing rates for other specific mutations associated with targeted therapies coincides with the approval of these new therapies by the US FDA. However, further education to increase molecular testing rates for specific mutations, improve prognostication, as well as to ensure the appropriate use of targeted therapies is required. The use of IHC rather than manual differential for blast enumeration, as recommended by the WHO, and the significant difference in enumeration method between LR- and HR-MDS pts, may be due to higher levels of fibrosis in HR pts and poor-quality aspirates rather than a lack of awareness of the recommendations; however, the recommended counting of 500 cells was not performed in all pts. Disclosures George: Novartis: Honoraria; Blueprint Medicines: Consultancy; Deciphera: Consultancy; Allakos: Consultancy. Garcia-Manero:Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding; Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding. Grinblatt:Celgene: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy. Komrokji:Incyte: Consultancy; DSI: Consultancy; Celgene: Consultancy; Agios: Consultancy; Janssen: Consultancy; Pfizer: Consultancy; Alexion: Speakers Bureau; Novartis: Speakers Bureau; Jazz: Speakers Bureau. Savona:Boehringer Ingelheim: Patents & Royalties; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Selvita: Membership on an entity's Board of Directors or advisory committees. Scott:Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Agios: Speakers Bureau. Sekeres:Millenium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees. Steensma:Stemline: Consultancy; Onconova: Consultancy; Aprea: Research Funding; Arrowhead: Equity Ownership; H3 Biosciences: Other: Research funding to institution, not investigator.; Astex: Consultancy; Summer Road: Consultancy; Pfizer: Consultancy. Flick:Celgene Corporation: Employment. Kiselev:Celgene Corporation: Employment, Equity Ownership. Louis:Celgene Corporation: Employment, Equity Ownership. Nifenecker:Celgene Corporation: Employment, Equity Ownership. Swern:Celgene Corporation: Employment, Equity Ownership. Foucar:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees.

Description: We generated MHC-independent chimeric antigen receptors (CARs) directed to the GD2 antigen expressed by neuroblastoma tumor cells and treated patients with this disease. Two distinguishable forms of this CAR were expressed in EBV-specific cytotoxic T lymphocytes (EBV-CTLs) and activated T cells (ATCs). We have previously shown that EBV-CTLs expressing GD2-CARs (CAR-CTLs) circulated at higher levels than GD2-CAR ATCs (CAR-ATCs) early after infusion, but by 6 weeks, both subsets became low or undetectable. We now report the long-term clinical and immunologic consequences of infusions in 19 patients with high-risk neuroblastoma: 8 in remission at infusion and 11 with active disease. Three of 11 patients with active disease achieved complete remission, and persistence of either CAR-ATCs or CAR-CTLs beyond 6 weeks was associated with superior clinical outcome. We observed persistence for up to 192 weeks for CAR-ATCs and 96 weeks for CAR-CTLs, and duration of persistence was highly concordant with the percentage of CD4+ cells and central memory cells (CD45RO+CD62L+) in the infused product. In conclusion, GD2-CAR T cells can induce complete tumor responses in patients with active neuroblastoma; these CAR T cells may have extended, low-level persistence in patients, and such persistence was associated with longer survival. This study is registered at www.clinialtrials.gov as #NCT00085930.

Description: Treatment of Epstein-Barr virus (EBV)–positive nasopharyngeal carcinoma (NPC) with EBV-specific cytotoxic T cells (EBV-specific CTL) has been promising, producing clinical responses. However, infused EBV-specific CTL did not expand in vivo, likely limiting their antitumor activity. Lymphodepleting patients with chemotherapy before T-cell transfer enhances in vivo T-cell expansion, but results in nonspecific destruction of the resident immune system and can have significant toxicity. To evaluate if monoclonal antibodies (mAbs) can produce a more selective lymphodepletion, we conducted a clinical study in which NPC patients received a pair of lymphodepleting mAbs targeted to the CD45 antigen (CD45 mAbs) before EBV-specific CTL infusion. Eight patients with recurrent NPC received CD45 mAbs followed by escalating doses of auto-logous EBV-specific CTL. Infusion of CD45 mAbs resulted in transient lymphopenia in all patients and an increase in interleukin-15 (IL-15) levels in 6 out 8 patients. All patients had an increase in their peripheral blood frequency of EBV-specific T cells after CTL infusion. Three patients with a persistent increase had clinical benefits including 1 complete response (〉 24 months) and 2 with stable disease (for 12 and 15 months). Lymphodepleting mAbs prior CTL transfer may represent an alternative to chemotherapy to enhance expansion of infused CTL. This study is registered at http://www.clinialtrials.gov as NCT00608257.

Description: Introduction: Outcomes among pts with AML have improved over the last 20 years with the introduction of novel, targeted, and reformulated chemotherapy agents, as well as the optimization of allogeneic hematopoietic stem cell transplantation (HSCT) strategies. The majority of pts, however, relapse after achieving remission, particularly those who are ineligible for or choose not to proceed to HSCT. To date, there is limited information available characterizing real-world Tx patterns of therapies offered to pts with AML who achieve complete remission (CR) or CR with incomplete hematologic recovery (CRi) and the subsequent impact on pt outcomes. Therefore, we analyzed data on post-remission therapy, including use of maintenance therapy, in pts with ND AML aged ≥ 55 years from the Connect® MDS/AML Disease Registry (NCT01688011), a large, multicenter, prospective observational cohort study of US pts with AML. Methods: Demographics, clinical characteristics, and Tx data were collected at the time of enrollment, and every 3 months during follow-up for pts enrolled in the Registry from Dec 2013 to the data cutoff for this analysis of Mar 2020. Pts were categorized as having received first-line therapy (intensive or non-intensive induction) or supportive care (including no Tx), based on medical records provided within 45 days of initial AML diagnosis. For pts achieving CR/CRi following induction, post-remission Tx was defined as: prolonged therapy (ongoing, non-intensive regimen similar to induction, administered until disease progression), consolidation (post-remission intensive chemotherapy), maintenance (non-intensive therapy administered for a prolonged period of time, with agent(s) not used during induction), and HSCT. Overall survival (OS), calculated from the time of CR/CRi, was determined using the Kaplan-Meier method. Results: As of Mar 2020, 638 pts with AML (median age 71 years; range 55−97) were enrolled in the Registry. The proportion of pts treated at community/government vs academic sites was 59% and 41%, respectively. A total of 587 ND AML pts had complete Tx data for analysis (evaluable population). Baseline characteristics are shown in the Table. Of the evaluable population, 299 (51%) received intensive induction, 280 (48%) non-intensive induction, and 8 (2%) supportive care only. A total of 233 (40%) evaluable pts achieved first CR/CRi following induction therapy: 183 received intensive induction and 50 received a non-intensive regimen. Tx patterns for pts achieving CR/CRi are shown in the Figure. Among the 587 evaluable pts, 108 (18%) received HSCT; of these, 81 (75%) proceeded to HSCT after achieving first CR/CRi with induction (77 [95%] received intensive induction, 4 [5%] received non-intensive induction) ± consolidation therapy. The most frequent reasons for transplant ineligibility were age (64%), comorbidities (49%), not achieving remission (30%), and Eastern Cooperative Oncology Group performance status (23%). Median OS was 48.2 months for pts in first CR/CRi who had HSCT vs 21.0 months for pts in first CR/CRi who did not. Among the 233 pts achieving CR/CRi, 51 (22%) received maintenance therapy: 36 (15%) had maintenance after induction ± consolidation, and 15 (6%) received maintenance therapy post HSCT. Median duration of maintenance was 112 days (range 3-786). Conclusions: Among pts with ND AML in the Connect® MDS/AML Disease Registry who achieved CR/CRi, more received an intensive induction regimen vs a non-intensive regimen. Additional time will be needed to accurately evaluate the impact of novel non-intensive induction regimens (e.g. IDH1/2 inhibitors, venetoclax, FLT3 inhibitors), which have shown improved remission rates and OS outcomes compared with prior low-intensity regimens. Fewer than one third of pts who achieved first CR/CRi following induction ± consolidation proceeded to HSCT, and those transplanted in first CR/CRi showed improved OS vs those without HSCT. These results suggest that real-world practices may tend to select younger, more fit pts with AML as candidates for intensive induction therapy and HSCT. Given that maintenance is not a widely established practice in AML, only 22% of pts in remission received maintenance therapy as a means to improve outcomes. This may change with the approval of novel therapies in the AML maintenance setting, which have the potential to prolong remission, delay relapse, and prolong OS following CR/CRi. Disclosures Roboz: Agios: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Array BioPharma: Consultancy; Bayer: Consultancy; Celltrion: Consultancy; Eisai: Consultancy; Jazz: Consultancy; Roche/Genentech: Consultancy; Sandoz: Consultancy; Actinium: Consultancy; Argenx: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; AstraZeneca: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; Takeda: Consultancy; Trovagene: Consultancy; Cellectis: Research Funding; Jasper Therapeutics: Consultancy; Epizyme: Consultancy; Helsinn: Consultancy; MEI Pharma: Consultancy; Celgene: Consultancy; Astex: Consultancy; Amphivena: Consultancy. Cogle:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Aptevo Therapeutics: Research Funding. Pollyea:Pfizer: Consultancy; Celgene/BMS: Consultancy; Takeda: Consultancy; Daiichi Sankyo: Consultancy; Abbvie: Consultancy, Research Funding; Syros: Consultancy; Syndax: Consultancy; Karyopharm: Consultancy; Novartis: Consultancy; Genentech: Consultancy; Amgen: Consultancy; Janssen: Consultancy; 47: Consultancy, Research Funding; Agios: Consultancy; Glycomimetics: Other. Abedi:AbbVie, BMS, Gilead Sciences, Seattle Genetics, Takeda: Speakers Bureau; BMS, Gilead Sciences: Research Funding. Thompson:Doximity: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Synapse Precision Medical Council: Other: Travel expenses; AIM Specialty Health, BMS, GlaxoSmithKline, Takeda, Via Oncology: Membership on an entity's Board of Directors or advisory committees. Nifenecker:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Flick:Bristol Myers Squibb: Current Employment. Kiselev:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Louis:Bristol Myers Squibb: Ended employment in the past 24 months. Little:Bristol Myers Squibb: Current Employment. Erba:AbbVie, Daiichi Sankyo, Forma, ImmunoGen, Jazz Pharmaceuticals, MacroGenics, Novartis, PTC: Research Funding; AbbVie, Agios, Celgene, Incyte, Jazz Pharmaceuticals, and Novartis: Speakers Bureau; AbbVie, Agios, Amgen, Astellas, Celgene, Daiichi Sankyo, Glycomimetics, ImmunoGen, Incyte, Jazz Pharmaceuticals, MacroGenics, Novartis, and Pfizer: Consultancy; Glycomimetics: Other: member of Scientific Steering Committee; Celgene: Other: chair of the Scientific Steering Committee; Covance (AbbVie): Other: chair of the Independent Review Committee.