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PURPOSE Adult T-cell lymphoma/leukemia (ATL) is a rare and aggressive peripheral T-cell malignancy caused by human T-cell lymphotropic virus-1 infection, which occurs in areas of high prevalence, predominantly in Japan and the Caribbean basin. Most ATL literature is derived from Japan and little is published about Caribbean patients. We describe the clinicopathologic characteristics and treatment outcomes of our Caribbean patients who have ATL at the State University of New York Downstate Medical Center and Kings County Hospital. PATIENTS AND METHODS We conducted a retrospective analysis of our patients with ATL who were diagnosed between 2005 and 2017. Medical records were reviewed for clinicopathologic data and treatment outcomes. The final analysis included acute and lymphomatous subtypes only. For the univariable analysis, outcomes were calculated by using a log-rank test, and survival curves were estimated by the Kaplan-Meier method. RESULTS We identified 63 patients with acute (55%) and lymphomatous (45%) subtypes, 95% of whom had Ann Arbor stage III to IV disease. The median age was 54 years, and the study population was predominantly female (65%). Most patients (82%) received first-line etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone (EPOCH) or cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) chemotherapy (10%) with an overall response rate of 46%. The median overall survival was 5.5 months, and the median progression-free survival was 4 months. Incidence of atypical immunophenotype (32%) was higher than previously reported in the Japanese literature and was associated with worse survival ( P = .04). Abnormal cytogenetics correlated with shorter progression-free survival ( P < .05). CONCLUSION We describe here the clinicopathologic characteristics and treatment outcomes of our Caribbean patients with aggressive ATL, which is largely chemotherapy resistant, and the challenges of treating a population with unmet medical needs.

Background Isocitrate dehydrogenase (IDH1 and IDH2) mutations commonly co-occur with FMS-like tyrosine kinase 3 (FLT3) mutations in patients with acute myeloid leukemia (AML). Methods The authors reviewed cases of patients with FLT3-internal tandem duplication (FLT3-ITD)-mutated AML with concurrent IDH mutations diagnosed between January 2011 and December 2018. Results A total of 91 patients with FLT3-ITD and IDH1 or IDH2 "double-mutated" AML were identified; 36 patients had concurrent FLT3-ITD/IDH1 mutations (18 in the frontline and 18 in the recurrent and/or refractory [R/R] setting) and 55 patients had concurrent FLT3-ITD/IDH2 mutations (37 in the frontline and 18 in the R/R setting). FLT3 and/or IDH inhibitors (FLT3Is and/or IDHIs) were given as a single agent or in combination with cytotoxic chemotherapy (CCT) or low-intensity therapy (LIT). Rates of complete remission (CR) plus CR with incomplete count recovery (CRi) with the use of CCT and FLT3Is were 100% and 64%, respectively, in patients in the frontline and R/R settings. CCT with IDHIs was given in 2 frontline patients and both achieved a CR. LIT with FLT3Is in the frontline and R/R settings demonstrated CR and CRi rates of 67% and 28%, respectively. Single-agent FLT3Is and IDHIs demonstrated limited activity with a CR and/or CRi rate of 14% in patients with disease in the R/R setting. Conclusions The combination of FLT3I-based therapy with CCT or LIT appeared to be effective in both the frontline and R/R settings among patients with FLT3-ITD/IDH co-mutated disease. Fewer patients with double-mutated disease received CCT or LIT with IDH1/2 inhibitor in the frontline setting; however, high response rates also were noted with this approach. Lay summary The prognostic influence of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) and isocitrate dehydrogenase (IDH) co-mutation status on outcomes in patients with acute myeloid leukemia receiving an FLT3 inhibitor, non-FLT3/IDH inhibitor-based regimens, or an IDH inhibitor is unclear. This is an important clinical question because multiple targeted therapies for FLT3 and IDH1/2 mutations have become available. The results of the current study demonstrated that a combination of a FLT3 inhibitor with cytotoxic chemotherapy or low-intensity therapy appears to be an effective approach in patients with FLT3-ITD/IDH co-mutated disease in both the frontline and recurrent and/or refractory settings. Fewer dual-mutated patients received cytotoxic chemotherapy or low-intensity therapy with an IDH1/2 inhibitor in the frontline setting; however, excellent responses also were observed with this approach.

The coronavirus disease (COVID‐19) pandemic has posed several challenges to the hematology community to re‐organize the medical care of patients with hematologic malignancies. Whereas the oncology societies favored a more or less conservative approach which considered the possibility of delaying treatment administration on a case‐by‐case basis, the hematology community guidelines were less stringent and recommended adequate individualized regimens. As countries are de‐escalating the lockdown and the medical community is unable to foresee the end of the current outbreak will and whether the pandemic would eventually come back as a seasonal infection, there is interest in screening of patients with hematology malignancies with COVID‐19 instead of limiting access to curative treatments. The rapidly accumulating knowledge about COVID‐19 allows a better understanding of the diagnostic tools that may be potentially used in screening. Herein, we briefly review the pathophysiology of COVID‐19, the rationale of screening of patients with hematologic malignancies, tools for screening, and available guidelines. This article is protected by copyright. All rights reserved.

Recent years have witnessed major advances that have improved outcome of adults with acute lymphoblastic leukemia (ALL). The emergence of the concept of measurable residual disease has fine-tuned our prognostic models and guided our treatment decisions. The treatment paradigms of ALL have been revolutionized with the advent of tyrosine kinase inhibitors targeting BCR-ABL1, monoclonal antibodies targeting CD20 (rituximab), antibody-drug conjugates targeting CD22 (inotuzumab ozogamicin), bispecific antibodies (blinatumomab), and CD19 chimeric antigen receptor T cell therapy (tisagenlecleucel). These highly effective new agents are allowing for novel approaches that reduce reliance on intensive cytotoxic chemotherapy and hematopoietic stem cell transplantation in first remission. This comprehensive review will focus on the recent advances and future directions in novel therapeutic strategies in adult ALL.

Burkitt leukemia/lymphoma (BL) and high-grade B-cell lymphoma (HGBL) have a high incidence of central nervous system (CNS) involvement, which is associated with poor prognosis. The hyper-cyclophosphamide, vincristine, Adriamycin, and dexamethasone plus rituximab (CVAD-R) regimen includes systemic and intrathecal CNS-directed therapy to treat and prevent CNS disease. We report here the long-term safety and efficacy of the hyper-CVAD-R regimen in adults with BL and HGBL, focusing on its efficacy to prevent CNS relapse. Among 79 adults (54 BL, 25 HGBL), the median age was 44 years (25% ≥60 years old), 73% had bone marrow (BM) involvement, and 28% had CNS involvement. The complete response rate was 91% (BL 96%; HGBCL 79%; P = .16). The 5-year relapse-free survival (RFS) and overall survival (OS) rates were 58% and 52%, respectively. The cumulative incidence of relapse (CIR) was 21% (BL 14%; HGBCL 37%, P = .06) and was associated with baseline BM (27% vs 0%; P = .02) and CNS (42% vs 12%; P < .01) involvement. In multivariate analyses, age and CNS involvement were independent predictors for OS and RFS. The 5-year CNS CIR was 6% (BL 4%; HGBL 11%; P = .31); 16% with baseline CNS involvement (P = .03). Our data support the use of hyper-CVAD-R in preventing CNS relapse, especially among high-risk patients with BM or CNS involvement.

This case highlights the first reported association of doxorubicin with takotsubo cardiomyopathy (TC) presenting as cardiogenic shock during the first continuous infusion in a patient with adult T‐cell leukemia/lymphoma. We aim to raise awareness to recognize and distinguish between irreversible doxorubicin‐associated cardiomyopathy and reversible doxorubicin‐associated TC in patients with cancer.

Metastatic spread from breast cancer to the gastrointestinal tract is rare. Such cases are predominantly lobular carcinomas and they usually occur later on during the course of disease progression with the stomach being the most common site involved. Furthermore, occult breast primary tumor is extremely uncommon. To the best of our knowledge, we describe here the first case of incidental colonic metastasis as first presentation of an occult breast ductal carcinoma. We also provide a review of the literature on gastrointestinal—and specifically colonic—involvement from breast ductal carcinoma.

Background The achievement of a 3-month complete molecular response (CMR) is a major prognostic factor for survival in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, 25% of patients relapse during therapy with tyrosine kinase inhibitors (TKIs). Methods The authors reviewed 204 patients with Ph-positive ALL who were treated between January 2001 and December 2018 using the combination of hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) plus a TKI (imatinib, 44 patients [22%]; dasatinib, 88 patients [43%]; or ponatinib, 72 patients [35%]). Progression-free survival (PFS) was defined as the time from the start date of therapy to the date of relapse, death, or last follow-up. Overall survival (OS) was defined as the time from the start date of therapy to the date of death or last follow-up. Results Overall, a 3-month CMR was observed in 57% of patients, including 32% of those who received imatinib, 52% of those who received dasatinib, and 74% of those who received ponatinib. The median follow-up was 74 months (imatinib, 180 months; dasatinib, 106 months; ponatinib, 43 months). Among 84 patients in 3-month CMR, 17 (20%) proceeded to undergo allogeneic stem cell transplantation (ASCT). The 5-year PFS and OS rates were 68% and 72%, respectively. By multivariate analysis, ponatinib therapy was the only significant favorable independent factor predicting for progression (P = .028; hazard ratio, 0.388; 95% CI, 0.166-0.904) and death (P = .042; hazard ratio, 0.379; 95% CI, 0.149-0.966). ASCT was not a prognostic factor for PFS and OS by univariate analysis. Conclusions In patients with Ph-positive ALL, ponatinib is superior to other types of TKIs in inducing and maintaining a CMR, thus preventing disease progression. ASCT does not improve outcome once a 3-month CMR is achieved.

Despite promising results with FLT3 inhibitors (FLT3i), response durations remain short. We studied pretreatment and relapse bone marrow samples from patients with FLT3-mutated acute myeloid leukemia (AML) treated with FLT3i-based therapies (secondary resistance cohort), and pretreatment bone marrow samples from patients with no response to FLT3i-based therapies (primary resistance cohort). Targeted next-generation sequencing (NGS) at relapse identified emergent mutations involving on-target FLT3, epigenetic modifiers, RAS/MAPK pathway, and less frequently WT1 and TP53. RAS/MAPK and FLT3-D835 mutations emerged most commonly following type I and II FLT3i-based therapies, respectively. Patients with emergent mutations at relapse had inferior overall survival compared with those without emergent mutations. Among pretreatment RAS-mutated patients, pretreatment cohort-level variant allelic frequencies for RAS were higher in nonresponders, particularly with type I FLT3i-based therapies, suggesting a potential role in primary resistance as well. These data demonstrate distinct pathways of resistance in FLT3-mutated AML treated with type I versus II FLT3i. Significance: Sequential NGS-based mutational analysis at relapse after FLT3i-based therapies showed distinct pathways of secondary resistance between type I and II FLT3i. FLT3 mutations may be lost at relapse after FLT3i-based therapies. Pretreatment RAS/MAPK mutations may also be associated with primary resistance in patients treated with type I FLT3i. See related commentary by Shastri et al., p. 113.

Background: The addition of tyrosine kinase inhibitors (TKIs) to chemotherapy has dramatically improved outcomes of patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). When allogeneic hematopoietic stem cell transplant (HSCT) is performed, maintenance TKI is generally given for a fixed duration. However, the optimal duration of TKI outside of HSCT remains unknown, and the common practice is to continue indefinitely. Here, we report characteristics and outcomes of 9 patients treated with chemotherapy + TKI without HSCT and later discontinued TKI. Methods: Among 188 patients with Ph-positive ALL who did not undergo HSCT, 9 of them discontinued maintenance TKI mainly due to side effects. Patients were closely monitored with serial PCR testing for the BCR-ABL1 transcript. Major molecular response (MMR) was defined as BCR-ABL1 transcript ≤0.1% on the international scale for p210 transcripts and a 3-log reduction from baseline for p190 transcripts. Deep molecular remission (DMR) was defined as the absence of quantifiable BCR-ABL1 transcripts with a sensitivity of 0.01%. Molecular relapse was defined as loss of MMR. Treatment-free remission (TFR) was defined from time of TKI discontinuation to molecular relapse, last follow-up, or death from any cause. Results: At the time of TKI discontinuation, transcript level was undetected in 6 patients, p = 0.096). Conclusion: TKI discontinuation outside of HSCT in Ph-positive ALL in the setting of compelling toxicity may be safe only among a highly selected group of patients with deep and prolonged DMR undergoing close and frequent monitoring. Validation of these findings in prospective clinical trials is highly needed.

Normal karyotype in therapy-related acute myeloid leukemia (t-AML) is rare and the relative contribution of prior exposure to chemotherapy or radiotherapy to outcomes in these patients remains uncertain. We performed a retrospective study of 742 patients with newly diagnosed AML and normal karyotype (t-AML, n = 61, and non-t-AML, n = 681). Patients with t-AML were older but had a similar mutational profile compared to those with non-t-AML. Overall survival (OS) and relapse-free survival (RFS) were significantly worse for patients with t-AML (P P = 0.02, respectively). Patients with t-AML had a higher cumulative incidence of death in remission (51% versus 16%, P P = 0.21). Both intensive induction and allogeneic hematopoietic stem cell transplantation in first remission were associated with improved OS and RFS in non-t-AML but not in t-AML. Overall, although disease biology appears similar between t-AML and non-t-AML with normal karyotype as indicated by similar risks of relapse, death in remission is the main driver of inferior outcome in t-AML. Careful therapeutic decisions are required to mitigate potential treatment-related toxicity in this rare subgroup of patients with t-AML and normal karyotype.

Background Unplanned 30-day readmissions are a frequent complication of acute leukemia therapy. However, there is limited data in acute lymphoblastic leukemia (ALL), with reported readmission rates (RaR) of 36% for pediatric ALL. Methods We retrospectively reviewed hospitalizations for ALL for adult patients >/= 18 years at our institution between January 2018 and December 2018. Unplanned readmissions were defined as any hospitalization within 30-days after discharge from the index admission, excluding all elective re-admissions for scheduled chemotherapy. Patients >/= 55 years of age receiving their initial induction therapy remained hospitalized for at least 21 days until bone marrow analysis and neutrophil count above 500/mm3. The primary objective was to identify the 30-day unplanned readmission rates, cause of readmissions, and predicted factors for readmissions. The secondary outcome included 30-day readmission mortality rate and inpatient mortality rate. Results There were a total of 841 ALL hospitalizations, 94 admissions for 63 pts (average 1.49 re-admit/pt) during frontline induction, 443 for 123 pts (average 3.6) during consolidation and 304 for 92 pts (average 3.3) with relapsed/refractory ALL (R/R ALL). The median age was 43 years for the frontline induction, 45 years for the consolidation group, and 42 years for R/R ALL patients. Baseline characteristics are listed in Table 1. The median length of index admission was 11 days for induction, 4 days during consolidation, and 8 days for R/R ALL. The 30-day unplanned RaR was 32% for induction, 28% for consolidation, and 36% for R/R ALL, with a median time to readmission of 6 days, 6 days, and 5 days, respectively. The most common causes of readmissions were infections (60%, 60% and 29% during induction, consolidation and R/R ALL respectively), including 30% neutropenic fever of unknown origin (NF), pain 20%, gastrointestinal infections 13%, neurologic causes (altered mental status, headache and LE weakness) 13%, and 10% bacteremia for induction; 19% neurologic causes, 17% NF, 15% upper respiratory infections, and11% pain during consolidation; and 9% bleeding, 8% NF, and 6% bacteremia for R/R ALL. (Figure 1) The median length of readmission was 5 days, 4 days, and 7 days for induction, consolidation, and R/R ALL patients, with a rate of ICU stay of 7%, 2%, and 18%, respectively. (Figure 2) While no significant differences were seen in the rate of ICU stay between readmissions and non-readmission for the induction and consolidation groups, R/R ALL patients had an increased incidence of ICU stay (18% vs. 11%, p=.001) and 30-day mortality (13% vs. 5% p=.010). We performed a logistical regression analysis to determine risk factors associated with readmissions. The multivariate analysis identified COPD (OR 3.30, p=.016) as an independent predictor for readmissions and male sex was associated with a decreased risk (OR 0.58, p=.016) during consolidation therapy; meanwhile, Philadelphia positive ALL (Ph+ALL) was negatively associated with RaR for R/R ALL pts (OR 0.33, p=.014). (Table 2) There was no significant association between the commonly used L.A.C.E. score and the risk of readmissions among consolidation and R/R ALL pts. However, during induction, a higher L.A.C.E score was negatively associated with the risk of readmission (OR 0.30, p=.027), likely due to a longer duration of hospital stay for high-risk patients (18 days vs. 8 days, p=.000). The 30-day mortality rate and inpatient mortality rate was 3% for unplanned induction readmissions, 0% for consolidation, and 13% for R/R ALL. One patient (3%) died after readmission during induction due to infection. The 30-day mortality rate after readmission for R/R ALL patients was 13%, with 50% of deaths due to infections and 30% due to disease progression. Conclusions Unplanned 30-day readmissions were frequent among patients with ALL, with similar rates between each sequential line of therapy, and the most common cause was infections. The 30-day mortality remains low for induction and consolidation pts, with a significantly higher risk for ICU stay and 30-day mortality for R/R ALL pts. We identified COPD, female sex, and non-Ph+ ALL as independent predictors for readmission. However, the majority of the pts were younger, with only 24-34% above 55 years of age. Implementing more frequent monitoring and increased precautions in high-risk pts could help reduce mortality in ALL. Disclosures Jain: Aprea Therapeutics: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Precision Bioscienes: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Fate Therapeutics: Research Funding; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Pfizer: Research Funding. Short:AstraZeneca: Consultancy; Astellas: Research Funding; Amgen: Honoraria; Takeda Oncology: Consultancy, Honoraria, Research Funding. Ravandi:Celgene: Consultancy, Honoraria; Orsenix: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Macrogenics: Research Funding; Xencor: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding. Borthakur:Abbvie: Research Funding; Curio Science LLC: Consultancy; Polaris: Research Funding; Jannsen: Research Funding; PTC Therapeutics: Consultancy; Argenx: Consultancy; PTC Therapeutics: Research Funding; GSK: Research Funding; FTC Therapeutics: Consultancy; Treadwell Therapeutics: Consultancy; BMS: Research Funding; AstraZeneca: Research Funding; Novartis: Research Funding; Incyte: Research Funding; Cyclacel: Research Funding; BioLine Rx: Consultancy; Xbiotech USA: Research Funding; BioLine Rx: Research Funding; Oncoceutics: Research Funding; BioTherix: Consultancy; Nkarta Therapeutics: Consultancy. Sasaki:Daiichi Sankyo: Consultancy; Novartis: Consultancy, Research Funding; Pfizer Japan: Consultancy; Otsuka: Honoraria. Cortes:Novartis: Consultancy, Research Funding; Merus: Research Funding; Immunogen: Research Funding; Bristol-Myers Squibb: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Amphivena Therapeutics: Research Funding; Arog: Research Funding; BiolineRx: Consultancy, Research Funding; Sun Pharma: Research Funding; Astellas: Research Funding; Telios: Research Funding; BioPath Holdings: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Kantarjian:Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Research Funding; Ariad: Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria; AbbVie: Honoraria, Research Funding; BMS: Research Funding; Novartis: Research Funding; Astex: Research Funding; Daiichi-Sankyo: Research Funding; Immunogen: Research Funding; Pfizer: Honoraria, Research Funding; Cyclacel: Research Funding; Jazz Pharma: Research Funding. Garcia-Manero:AbbVie: Honoraria, Research Funding; Acceleron Pharmaceuticals: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Helsinn Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Merck: Research Funding; Astex Pharmaceuticals: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Amphivena Therapeutics: Research Funding. Jabbour:AbbVie: Other: Advisory role, Research Funding; Pfizer: Other: Advisory role, Research Funding; BMS: Other: Advisory role, Research Funding; Amgen: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding; Takeda: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding. Kadia:Incyte: Research Funding; Celgene: Research Funding; Cellenkos: Research Funding; Genentech: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Cyclacel: Research Funding; Novartis: Honoraria; Pulmotec: Research Funding; Abbvie: Honoraria, Research Funding; Ascentage: Research Funding; Astra Zeneca: Research Funding; Amgen: Research Funding; Pfizer: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Astellas: Research Funding.

Background Unplanned 30-day readmissions are a frequent complication of acute myeloid leukemia (AML) therapy, with rates of 30-60% from published studies, including a 30% readmission rate (RaR) for induction and 40-50% RaR during consolidation. However, the data is still limited regarding predictors for readmissions. Methods We retrospectively reviewed hospitalizations for AML for adult patients >/= 18 years at our institution between January 2018 and December 2018. Unplanned readmissions were defined as any hospitalization within 30-days after discharge from the index admission, excluding all elective re-admissions for scheduled chemotherapy. Patients >/= 60 years of age receiving their initial induction therapy remained hospitalized for at least 21 days until bone marrow analysis and neutrophil count above 500/mm3. The primary objective was to identify the 30-day unplanned readmission rates, cause of readmissions, and predicted factors for readmissions. The secondary outcome included 30-day readmission mortality rate and inpatient mortality rate. Results There were a total of 1681 AML hospitalizations, 393 admissions for 273 pts (average 1.44 re-admit/pt) during frontline induction, 364 for 179 pts (average 2.03) during consolidation and 924 for 298 pts (average 3.1) with relapsed/refractory AML (R/R AML). The median age was 68 years for the frontline induction and consolidation groups and 60 years for R/R AML patients. Baseline characteristics are listed in Table 1. The median length of index admission was 21 days for induction, 4 days during consolidation, and 7 days for R/R AML. The 30-day unplanned RaR was 27% for induction, 30% for consolidation, and 46% for R/R AML, with a median time to readmission of 7 days, 11 days, and 7 days, respectively. The most common causes of readmissions were infections (80%, 75% and 75% during induction, consolidation and R/R AML respectively), including 39% neutropenic fever of unknown origin (NF), 13% pneumonia, and 8% bacteremia for induction; 24% NF, 20% pneumonia and 11% gastrointestinal infections during consolidation; and 18% NF, 20% pneumonia and 14% bacteremia for R/R AML. (Figure 1) The median length of readmission was 6 days for frontline pts and 8 days for R/R AML. The rate of ICU stay was 9% for induction, and 22% for consolidation, and 18% for R/R AML. (Figure 2). There was a significant increase of ICU stay for readmissions during consolidation (22% vs 5%, p=0.010) and R/R AML (18% vs 10% p= We confirmed hypoalbuminemia (OR 3.42; p= 0.006), thrombocytopenia (OR 2.10; p= 0.015) and history of diabetes (OR 1.93; p= 0.020) as an independent predictor for readmissions during induction by multivariate analysis, while history of diabetes was significantly associated with increased risk of readmission for consolidation (OR 1.69; p=0.04) and neutropenia (OR 1.32, p= The 30-day mortality rate and inpatient mortality rate was 6% for unplanned induction readmissions, 11% for consolidation, and 18% for R/R AML. With the exception of induction, there was a higher incidence of 30-mortality for unplanned re-admissions during consolidation and R/R AML. The most common causes of death after readmission were infections with 57% for induction, 70% for consolidation, and 73% for R/R AML pts. Conclusions Unplanned 30-day readmissions, most commonly due to infection, were common among patients with AML, with rates increasing with each sequential line of therapy. While the 30-day mortality and ICU admissions remain low for induction pts, those receiving consolidation or with R/R AML had significantly higher rates. We identified several factors, including hypoalbuminemia, thrombocytopenia, neutropenia and diabetes, as independent predictors for readmission. Implementing more frequent monitoring or trading increased length-of-stay for RaR in high-risk pts could help reduce mortality in AML. Disclosures Pemmaraju: Plexxikon: Research Funding; Incyte Corporation: Honoraria; Stemline Therapeutics: Honoraria, Research Funding; Cellectis: Research Funding; AbbVie: Honoraria, Research Funding; MustangBio: Honoraria; Celgene: Honoraria; Pacylex Pharmaceuticals: Consultancy; Affymetrix: Other: Grant Support, Research Funding; Samus Therapeutics: Research Funding; Daiichi Sankyo: Research Funding; DAVA Oncology: Honoraria; Roche Diagnostics: Honoraria; SagerStrong Foundation: Other: Grant Support; Blueprint Medicines: Honoraria; LFB Biotechnologies: Honoraria; Novartis: Honoraria, Research Funding. DiNardo:Takeda: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; MedImmune: Honoraria; ImmuneOnc: Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria, Research Funding; Syros: Honoraria; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Jazz: Honoraria; Novartis: Consultancy; Calithera: Research Funding; Notable Labs: Membership on an entity's Board of Directors or advisory committees. Daver:Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding; Servier: Research Funding; Genentech: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novimmune: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trovagene: Research Funding; Fate Therapeutics: Research Funding; ImmunoGen: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Trillium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees. Borthakur:Oncoceutics: Research Funding; Nkarta Therapeutics: Consultancy; Treadwell Therapeutics: Consultancy; BioTherix: Consultancy; Novartis: Research Funding; AstraZeneca: Research Funding; Incyte: Research Funding; Abbvie: Research Funding; Jannsen: Research Funding; GSK: Research Funding; Cyclacel: Research Funding; BioLine Rx: Research Funding; Polaris: Research Funding; Xbiotech USA: Research Funding; BioLine Rx: Consultancy; FTC Therapeutics: Consultancy; PTC Therapeutics: Research Funding; PTC Therapeutics: Consultancy; Argenx: Consultancy; Curio Science LLC: Consultancy; BMS: Research Funding. Cortes:Immunogen: Research Funding; Bristol-Myers Squibb: Research Funding; BiolineRx: Consultancy, Research Funding; Arog: Research Funding; Amphivena Therapeutics: Research Funding; Astellas: Research Funding; Telios: Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Merus: Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sun Pharma: Research Funding; BioPath Holdings: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Consultancy, Research Funding. Ravandi:Amgen: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Xencor: Consultancy, Honoraria, Research Funding; Macrogenics: Research Funding; Orsenix: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria. Kantarjian:Astex: Research Funding; Daiichi-Sankyo: Research Funding; Immunogen: Research Funding; Cyclacel: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Research Funding; Novartis: Research Funding; Agios: Honoraria, Research Funding; Ariad: Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria; AbbVie: Honoraria, Research Funding; BMS: Research Funding; Pfizer: Honoraria, Research Funding. Garcia-Manero:Novartis: Research Funding; Helsinn Therapeutics: Consultancy, Honoraria, Research Funding; Acceleron Pharmaceuticals: Consultancy, Honoraria; Amphivena Therapeutics: Research Funding; H3 Biomedicine: Research Funding; Jazz Pharmaceuticals: Consultancy; Astex Pharmaceuticals: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Merck: Research Funding; Onconova: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Kadia:Ascentage: Research Funding; Astra Zeneca: Research Funding; Novartis: Honoraria; Amgen: Research Funding; Pulmotec: Research Funding; Astellas: Research Funding; Cyclacel: Research Funding; JAZZ: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Incyte: Research Funding; Celgene: Research Funding; Cellenkos: Research Funding.

Context BL and HGBCL have a propensity for CNS involvement, which confers poor prognosis. Standard of care includes dose-intense chemoimmunotherapy (Hyper-CVAD or CODOX/MVAC with rituximab [R]). Despite favorable efficacy and tolerability of DA-EPOCH-R, outcomes are poor in patients with bone marrow (BM)/CNS disease with high rates of CNS relapse due to the lack of systemic directed CNS therapy (13%; Zayac ASH 2019). Objective To report the long-term outcomes with Hyper-CVAD-R in adults with BL and HGBCL. Main outcomes measured We evaluated complete remission (CR) rates, relapse- free survival (RFS), overall survival (OS), and cumulative incidence of relapse (CIR). Results Seventy-nine patients treated between 2000 and 2018 met WHO 2017 criteria (BL 54, HGBCL 25). Median age was 44 years (18–77 years); 25% were older than 60 years old. Most patients had high-risk disease; 73% BM involvement, 28% CNS involvement, and 63% had LDH > 3 times the normal level. Among the 25 patients with HGBCL, 7 (28%) had double-hit lymphomas (BCL-2 rearrangement), and the median international prognostic index was 3.5 (range 2–5). The CR rate was 91% (BL 96%; HGBCL 79%; P=0.16), and the 30-day mortality was 3%. The 5-year OS and RFS rates were 52% (BL 55%; HGBCL 44%; P=0.86) and 58% (BL 59%; HGBCL 57%; P=0.62), respectively. The CIR was 21% (BL 14%; HGBCL 37%, P=0.06); associated with BM involvement (27% vs 0%; P=0.02) and CNS involvement (42% vs 12%; P Conclusion Our data support the efficacy of Hyper-CVAD-R in preventing CNS relapse, especially among high-risk patients with BM or CNS involvement.

Context The combination of tyrosine kinase inhibitors (TKI) with intensive chemotherapy improves outcome of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-pos ALL), particularly among patients in molecular response within three months of therapy. Objective The aim of this study is to identify prognostic factors for relapse and/or death in patients with Ph-pos ALL after 3 months of therapy. Design Retrospective analysis of patients who enrolled on prospective clinical trials of the combination of hyper-CVAD (HCVAD) with a TKI. Setting MD Anderson Cancer Center. Patients or other participants We analyzed 204 patients with newly diagnosed Ph-pos ALL who were treated with HCVAD with a TKI; imatinib (N=44), dasatinib (N=88), and ponatinib (N=72). Interventions Molecular response was assessed at CR, at 3 months, every 3 months during the first 2 years, and every 3-6 months thereafter. Allogeneic stem cell transplantation was offered at the discretion of patient and treating physician. Ponatinib dose was reduced to 15 mg daily, once CMR is achieved. Main outcome measures Progression -free survival (PFS) was calculated from the date of treatment initiation until date of relapse, or death. Overall survival (OS) was calculated from the time of treatment initiation until death. Results By multivariate analysis for PFS and OS in patients who achieved CMR within 3 months of therapy, ponatinib therapy was the only significant independent factor predicting for progression (P=0.028; hazard ratio [HR], 0.388; 95% confidence interval [CI], 0.166-0.904) and death (P=0.042; HR, 0.379; 95% CI, 0.149-0.966); among patients who did not achieve CMR within 3 months, the achievement of major molecular response was a favorable prognostic factor. Though the number of patients with MMR and without molecular response (i.e., no CMR/MMR) is limited, there was a tendency of improved PFS in patients who received allogeneic stem cell transplant. Conclusions The achievement of CMR within 3 months of therapy is the landmark for long-term survival. Ponatinib maintains CMR, and prevents relapse and death in patients with newly diagnosed Ph-pos ALL. MMR within 3 months was associated with improved survival compared to the lack of MMR within 3 months of TKI therapy.

Context Limited data are available on the outcome of adults with relapsed-refractory (R/R) T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL). Objective We aimed to identify factors predictive for long-term survival and to establish the benchmark for expected outcomes in this setting. Main outcomes measured We reviewed characteristics and outcome of adults with R/R T-cell ALL or LBL treated at our institution between 2009 and 2019. We assessed response to salvage therapy and overall survival. To determine prognostic factors for survival, we performed univariate and multivariate analyses using the following baseline characteristics: age, disease type (ALL versus LBL), immunophenotypic subtype (early T-cell precursor [ETP] versus non-ETP), complex cytogenetics, central nervous system involvement at salvage, first complete remission (CR1) duration Results We identified 82 patients, including 39% in S1, 27% in S2, and 34% in S3+. ETP subtype was present in 35% of cases, and 16% had complex cytogenetics. Salvage therapy included standard-of-care regimens in 48 patients (59%), including nelarabine-based therapy in 21 patients (26%), pediatric-inspired asparaginase-based therapy in 11 patients (13%), clofarabine-based therapy in 9 patients (11%), and investigational-based therapies in 34 patients (41%), mainly venetoclax-based (18 patients; 22%). The CR/complete remission with incomplete hematological recovery (CRi) rate was 46%, with a median duration of response of 4 months. With a median follow-up of 37 months, the median OS was 8 months, and the 2-year OS was 23%. Only 14 patients were alive in remission at their last follow-up. In multivariate analysis, earlier salvage therapy was the only predictor for better survival (hazard ratio 0.57 [95% confidence interval, 0.33-0.99], P=0.049). A 3-month landmark analysis showed a survival benefit for consolidative hematopoietic stem cell transplant (HSCT) after CR to salvage therapy (2-year OS rate of 56% versus 24%, P=0.002). Conclusions The current study highlights the continuous unmet need of patients with R/R T-cell ALL treated with contemporary standard regimens and provides a reference for future clinical trials in this population.

The emergence of immunotherapy has provided significant clinical improvements in the treatment of metastatic solid tumors. Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) has dismal prognosis with median survival ranging between 6and12 months. Our aim is to review the current knowledge on the role of the immune system and immune checkpoint inhibitors in HNSCC. We will focus on the landmark trials that led to the regulatory approvals of pembrolizumab and nivolumab, and discuss a few promising contenders in clinical development and highlight the need to identify better biomarkers other than programmed death-ligand 1 to improve patient selection and help predict response.

Primary pulmonary Hodgkin's lymphoma (PPHL) is an uncommon disease. This entity is different from Hodgkin’s lymphoma with parenchymal or nodal lung involvement. In this report, we highlight the case of a young female presenting with a six-month history of a productive cough and constitutional B symptoms. Imaging showed cavitary lesions in the right-upper and right-middle lobes. The initial comprehensive infectious workup was negative. Histopathology and immunochemistry confirmed the diagnosis of PPHL. PPHL is an uncommon etiology of cavitary lung lesions. Despite its diagnostic difficulties, awareness of such a disease is crucial, given its high rate of response to treatment, especially in the young population.

Background: We have previously shown that CMR predicts better outcomes in Ph+ ALL. The lack of achievement of CMR and particularly major molecular response (MMR) at 3 months may confer poor outcomes. We sought to investigate the outcomes of pts who did not achieve CMR at 3 months as best response in terms of progression free survival (PFS) and overall survival (OS), and the role of allogeneic stem cell transplant (ASCT) in this population. Methods: We reviewed 204 pts with newly diagnosed Ph+ ALL treated at our institution between January 2001 and June 2019 with the combination of Hyper-CVAD plus tyrosine kinase inhibitors (TKI); dasatinib (n=88, 43%), ponatinib (n=72, 35%) and imatinib (n= 44, 22%). PFS was defined from the start of therapy to relapse or death. OS was defined from diagnosis to death or last follow-up. Backward multivariate Cox regression was used to identify prognostic factors for PFS and OS after variable selection at a p-value cutoff of 0.200. Time to ASCT was handled as a time-dependent variable. Survival curves were estimated by Kaplan-Meier method. Landmark analysis at the median time to ASCT was analyzed to evaluate the impact of ASCT. Results: We identified 94 pts (46%) who did not achieve 3-month CMR. Of pts treated with imatinib, 29 (66%) did not achieve 3-month CMR and 16 pts (36%) achieved 3-month MMR. Of pts treated with dasatinib, 42 (48%) did not achieve 3-month CMR and 29 pts (33%) achieved 3-month MMR. Of pts treated with ponatinib, 23 (32%) did not achieve 3-month CMR and 17 pts (24%) achieved 3-month MMR. Patient characteristics are summarized in table 1. Median age was 54 years (range: 21-80). The TKI administered was dasatinib, imatinib and ponatinib in 42 (45%), 29 (31%) and 23 (24%) pts, respectively. Overall, ASCT was performed in 28 pts (30%); 21 out of 62 pts (34%) with 3-month MMR, and 7 out of 32 pts (22%) who did not achieve MMR, within a median time of 5 months (range, 2.3-12.3). After a median follow-up of 97 months, median PFS was 21 months and median OS was 46 months. There was no difference in survival by TKI choice. The 5-year PFS and OS rates were 52% and 23% (p=0.001) (Figure 1A), and 58% and 26% (p=0.001) (Figure 1B) for pts with and without 3-month MMR, respectively. In multivariate analysis (table 2), 3-month MMR predicted longer PFS (p A 5-month landmark analysis was performed to assess the effect of ASCT on survival by 3-month MMR status. In pts who achieved 3-month MMR, 5-year PFS and OS rates were 60% and 58% (p=0.64) (Figure 2A) and 64% and 64% (p=0.73) (Figure 2B) in pts with and without ASCT, respectively. In contrast, among pts who did not achieve a 3-month MMR, there was a tendency for better PFS (5-PFS, 43% vs 21%; p=0.25) (Figure 2C) and OS (5-year OS, 43% vs. 26%; p=0.57) (Figure 2D) in favor of ASCT. Conclusions: The lack of achievement of MMR at 3 months predicted worse outcomes in Ph+ ALL. Higher survival rates were seen when ASCT was performed in pts who do not achieve 3-month MMR. Innovative targeted strategies aimed to eradicate minimal residual disease are needed to further improve long term outcomes. Disclosures Kantarjian: Cyclacel: Research Funding; AbbVie: Honoraria, Research Funding; BMS: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Research Funding; Jazz Pharma: Research Funding; Astex: Research Funding; Daiichi-Sankyo: Research Funding; Takeda: Honoraria; Amgen: Honoraria, Research Funding; Ariad: Research Funding; Immunogen: Research Funding; Agios: Honoraria, Research Funding; Novartis: Research Funding. Sasaki:Otsuka: Honoraria; Pfizer: Consultancy. Short:AstraZeneca: Consultancy; Takeda Oncology: Consultancy, Research Funding; Amgen: Honoraria. Khoury:Stemline Therapeutics: Research Funding; Angle: Research Funding; Kiromic: Research Funding. Champlin:Actinium: Consultancy; Johnson and Johnson: Consultancy; Sanofi-Genzyme: Research Funding. Kebriaei:Amgen: Research Funding; Jazz: Consultancy; Pfizer: Honoraria; Kite: Honoraria. Cortes:Forma Therapeutics: Consultancy, Honoraria, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; BiolineRx: Consultancy; Takeda: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Sun Pharma: Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Research Funding. Garcia-Manero:Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. Kadia:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bioline RX: Research Funding; BMS: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Research Funding. Borthakur:AstraZeneca: Research Funding; NKarta: Consultancy; Cyclacel: Research Funding; GSK: Research Funding; Xbiotech USA: Research Funding; Oncoceutics: Research Funding; Janssen: Research Funding; Incyte: Research Funding; Oncoceutics, Inc.: Research Funding; Eli Lilly and Co.: Research Funding; BMS: Research Funding; Tetralogic Pharmaceuticals: Research Funding; Strategia Therapeutics: Research Funding; Polaris: Research Funding; Arvinas: Research Funding; Merck: Research Funding; Cantargia AB: Research Funding; FTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Argenx: Membership on an entity's Board of Directors or advisory committees; BioTheryX: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; AbbVie: Research Funding; Bayer Healthcare AG: Research Funding; PTC Therapeutics: Consultancy; BioLine Rx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agensys: Research Funding; Eisai: Research Funding. Verstovsek:Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Promedior: Research Funding; CTI BioPharma Corp: Research Funding; Genetech: Research Funding; Blueprint Medicines Corp: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Research Funding; Pharma Essentia: Research Funding; Astrazeneca: Research Funding; Ital Pharma: Research Funding; Protaganist Therapeutics: Research Funding; Constellation: Consultancy; Pragmatist: Consultancy; Incyte: Research Funding. Daver:Agios: Consultancy; Hanmi Pharm Co., Ltd.: Research Funding; Genentech: Consultancy, Research Funding; Forty-Seven: Consultancy; Novartis: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; NOHLA: Research Funding; Glycomimetics: Research Funding; Otsuka: Consultancy; Celgene: Consultancy; Immunogen: Consultancy, Research Funding; Jazz: Consultancy; Astellas: Consultancy; BMS: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Servier: Research Funding; Abbvie: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Jain:Janssen Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Cellectis: Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, an AbbVie company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Konopleva:F. Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Ascentage: Research Funding; Kisoji: Consultancy, Honoraria; Reata Pharmaceuticals: Equity Ownership, Patents & Royalties; Ablynx: Research Funding; Astra Zeneca: Research Funding; Agios: Research Funding; Cellectis: Research Funding; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Eli Lilly: Research Funding; Forty-Seven: Consultancy, Honoraria; Calithera: Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding. O'Brien:Eisai: Consultancy; Gilead: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Kite: Research Funding; GlaxoSmithKline: Consultancy; Regeneron: Research Funding; TG Therapeutics: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Verastem: Consultancy; Vaniam Group LLC: Consultancy; Celgene: Consultancy; Astellas: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Acerta: Research Funding; Alexion: Consultancy; Amgen: Consultancy; Aptose Biosciences, Inc: Consultancy. Ravandi:Cyclacel LTD: Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Macrogenix: Consultancy, Research Funding; Menarini Ricerche: Research Funding; Selvita: Research Funding; Xencor: Consultancy, Research Funding. Jabbour:Adaptive: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Cyclacel LTD: Research Funding.

Background: Outcome of Ph+ALL has changed drastically with the availability of tyrosine kinase inhibitors (TKIs). We showed that 3-month CMR is a major factor predicting overall survival (OS). However, despite the achievement of CMR, 25% of pts progressed. The aim of this analysis is to assess the prognostic factors for progression and survival, and subsequently to assess the role of allogeneic stem cell transplant (ASCT) in pts who achieved CMR within 3 months of therapy. Methods: We performed a retrospective chart review of 204 pts with Ph+ ALL treated, at our institution between 01/2001 and 12/2018, with the combination of hyper-CVAD (HCVAD) with a TKI; imatinib, 44 (22%); dasatinib, 88 (43%); and ponatinib, 72 (35%). Among these pts, 3-month CMR was observed in 84 (41%); 11 (25%) with imatinib; 29 (33%) pts with dasatinib; and 44 (61%) with ponatinib. Poor risk cytogenetic abnormality was defined as the presence of +der(22)t(9;22) and/or −9/9p in the absence of high hyperdiploidy (51‐65 chromosomes). Progression-free survival (PFS) was defined as the time from the start date of therapy to the date of relapse, death, or the date of last follow-up. OS was defined as from the start date of therapy to the date of death or the date of last follow-up. To identify prognostic factors for PFS and OS, we performed backward multivariate Cox regression with the variable selection with a p-value cutoff of 0.200 by univariate Cox regression analysis. Time to ASCT was handled as a time-dependent variable. We performed landmark analysis to assess the impact of ASCT on PFS and OS. Results: Patient characteristics are summarized in Table 1. The median age was 48 years. 47% of pts (n=44) received ponatinib; 39% (n=29), dasatinib; 13% (n=11), imatinib. 77% of pts (n=65) had P190 transcript. Only 22% (n=15/67) had poor cytogenetic abnormalities with der(22)t(9;22) or del9p/-9 in the absence of high hyperdiploidy. The median follow-up was 64 months. Overall, the median PFS and OS was 125 and 125 months, respectively (Figure 1). The 5-years PFS and OS rates were 68% and 72%. The 5-years PFS rates by TKI were 64% for HCVAD-imatinib, 54% for HCVAD-dasatinib, and 81% for HCVAD-ponatinib. The respective 5-years OS rates were 64%, 62%, and 84% (Figure 2). By multivariate analysis for PFS and OS, ponatinib therapy was the only significant independent factor predicting for progression (P=0.028; hazard ratio [HR], 0.388; 95% confidence interval [CI], 0.166-0.904) and death (P=0.042; HR=0.379; 95% CI, 0.149-0.966) (Table 2). ASCT was not prognostic factor for PFS (P=0.902; HR, 0.941; 95% CI, 0.355-2.490) and OS (P=0.913; HR, 1.057; 95% CI, 0.393-2.838) by univariate analysis. We investigated the outcome of ASCT. 17 (20%) pts (imatinib n=2, dasatinib n=8, ponatinib n=7) received ASCT in CMR within a median of 4 months. After performing a landmark analysis at 4 months, there was no difference in PFS and OS among pts who received ASCT and those who did not, regardless of the TKI used (analysis performed overall and by TKI) (Figure 3). Conclusion: CMR predicts for the best long-term outcome. ASCT does not improve outcome once a CMR is achieved. Ponatinib is superior to other type of TKIs in inducing and maintaining CMR, and thus preventing progression. Disclosures Sasaki: Otsuka: Honoraria; Pfizer: Consultancy. Kantarjian:Agios: Honoraria, Research Funding; Immunogen: Research Funding; BMS: Research Funding; Jazz Pharma: Research Funding; Cyclacel: Research Funding; Amgen: Honoraria, Research Funding; Novartis: Research Funding; Pfizer: Honoraria, Research Funding; Astex: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; AbbVie: Honoraria, Research Funding; Daiichi-Sankyo: Research Funding; Ariad: Research Funding. Short:Amgen: Honoraria; Takeda Oncology: Consultancy, Research Funding; AstraZeneca: Consultancy. Khoury:Kiromic: Research Funding; Stemline Therapeutics: Research Funding; Angle: Research Funding. Konopleva:Astra Zeneca: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Kisoji: Consultancy, Honoraria; Ablynx: Research Funding; Agios: Research Funding; Cellectis: Research Funding; Amgen: Consultancy, Honoraria; F. Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Reata Pharmaceuticals: Equity Ownership, Patents & Royalties; Forty-Seven: Consultancy, Honoraria; Ascentage: Research Funding; Eli Lilly: Research Funding; Calithera: Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding. Jain:Janssen Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics, an AbbVie company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. DiNardo:abbvie: Consultancy, Honoraria; celgene: Consultancy, Honoraria; jazz: Honoraria; agios: Consultancy, Honoraria; syros: Honoraria; medimmune: Honoraria; daiichi sankyo: Honoraria; notable labs: Membership on an entity's Board of Directors or advisory committees. Garcia-Manero:Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. Kadia:Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bioline RX: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; BMS: Research Funding. Wierda:Miragen: Research Funding; Loxo Oncology Inc.: Research Funding; Gilead Sciences: Research Funding; Acerta Pharma Inc: Research Funding; Cyclcel: Research Funding; GSK/Novartis: Research Funding; Xencor: Research Funding; Pharmacyclics LLC: Research Funding; Genentech: Research Funding; Sunesis: Research Funding; KITE pharma: Research Funding; Janssen: Research Funding; Juno Therapeutics: Research Funding; Oncternal Therapeutics Inc.: Research Funding; AbbVie: Research Funding. Daver:Hanmi Pharm Co., Ltd.: Research Funding; Servier: Research Funding; Genentech: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Jazz: Consultancy; Forty-Seven: Consultancy; Jazz: Consultancy; Daiichi Sankyo: Consultancy, Research Funding; Hanmi Pharm Co., Ltd.: Research Funding; Novartis: Consultancy, Research Funding; Immunogen: Consultancy, Research Funding; Forty-Seven: Consultancy; Servier: Research Funding; Sunesis: Consultancy, Research Funding; Astellas: Consultancy; BMS: Consultancy, Research Funding; Celgene: Consultancy; Abbvie: Consultancy, Research Funding; Agios: Consultancy; Otsuka: Consultancy; Sunesis: Consultancy, Research Funding; Glycomimetics: Research Funding; Incyte: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Agios: Consultancy; Pfizer: Consultancy, Research Funding; Glycomimetics: Research Funding; Celgene: Consultancy; NOHLA: Research Funding; Karyopharm: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Otsuka: Consultancy; NOHLA: Research Funding; Abbvie: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Immunogen: Consultancy, Research Funding; Astellas: Consultancy. Thompson:Pfizer: Research Funding; Pharmacyclics: Research Funding; Genentech: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Research Funding; Amgen: Consultancy, Research Funding. Cortes:Novartis: Consultancy, Honoraria, Research Funding; Sun Pharma: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; Takeda: Consultancy, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; BiolineRx: Consultancy. O'Brien:Astellas: Consultancy; Aptose Biosciences, Inc: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Acerta: Research Funding; Alexion: Consultancy; Amgen: Consultancy; Celgene: Consultancy; Eisai: Consultancy; Gilead: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Kite: Research Funding; Janssen: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Regeneron: Research Funding; Sunesis: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Vaniam Group LLC: Consultancy; Verastem: Consultancy. Ravandi:Menarini Ricerche: Research Funding; Macrogenix: Consultancy, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Selvita: Research Funding; Cyclacel LTD: Research Funding; Xencor: Consultancy, Research Funding. Jabbour:Cyclacel LTD: Research Funding; Pfizer: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding.

Background: Treatment of Ph+ ALL has significantly improved since the addition of TKIs to chemotherapy, with improvement in complete molecular remission (CMR) and overall survival (OS) rates. However, the optimal duration of TKI is not yet established and the common practice is to continue indefinitely unless allogeneic stem cell transplant (ASCT) is performed. In pediatric setting, when TKIs were discontinued after 2 years of maintenance, high rates of relapse were seen, fortunately salvaged with ASCT and other approaches (Slayton WB et al; JCO. 2018 and Schultz KR; Leukemia 2014). In chronic myeloid leukemia, patients (pts) who achieve deep and sustained molecular remissions on TKI may be able to stop therapy successfully. Herein, we reviewed outcome of pts with Ph+ ALL treated with chemotherapy + TKI without ASCT who later discontinued TKI mainly due to adverse events. Methods: We reviewed 240 pts treated at our institution on sequential protocols with Hyper-CVAD chemotherapy + TKI (dasatinib [n=100], ponatinib [n=84], or imatinib [n=56]) between 2001 and 2019. We identified 9 pts (4%) in whom TKI was discontinued, 4 (44.5%) post dasatinib therapy, 4 (44.5%) post imatinib therapy, and 1 (11%) post ponatinib. We analyzed their characteristics and outcomes including molecular relapse rates and treatment-free remission (TFR). Pts were closely monitored with monthly PCR for the first 3 months, then every other month for 3 months, then every 3 months thereafter. Molecular relapse was defined as the loss of MMR (PCR>0.1%) or positivity of PCR at two assessments within a 2-week period. TKI was resumed upon molecular relapse. TFR was defined from the date of TKI discontinuation to molecular relapse or last-follow-up. Kaplan-Meier method was used for survival analysis. Results: Baseline characteristics are summarized in table 1. The median follow up from the time of diagnosis was 138 months (range: 40-190). The median age at diagnosis was 60 years (range: 20-80). Transcript type was p190 BCR-ABL1 in 7 pts (78%). Median time to CMR was 3 months (range: 0.4-120). Median duration of TKI therapy prior to discontinuation was 70 months (range: 23-143). Median duration of CMR before TKI stop was 52 months (range: 22-141). Reasons for stopping TKI were side effects in 8/9 pts, and physician's choice in 1 pt (after completing 2+ years of maintenance). At the time of TKI stop, 8 pts were in CMR, and 1 pt with low positive transcript level (0.01%). Median follow-up post TKI discontinuation was 37 months (range: 9-75). None of the pts had morphological relapse. Three pts (33%) had molecular relapse within a median of 6 months (range: 0.8-13.2 months). All 3 resumed TKI therapy: 2 of them regained MMR after a median of 4 months (range: 4.0-4.6 months); third pt continues to respond; the BCR-ABL1 transcripts down from 17.68% to 0.36% after 7 months (Table 2). Six pts remain alive and 3 pts died of disease-unrelated causes. The median TFR was not reached; 3-y TFR was 65% (Figure 1). Though the number of pts was only 9, the duration of CMR had a tendency of successful TFR (P=0.062; HR, 0.09; [95% CI, 0.009-1.119] with duration of CMR for 2 years, and P=0.137; HR, 0.15; [95% CI, 0.01-1.80] with duration of CMR for 3 years, as a binomial variable). The median duration of CMR in pts who relapsed and who did not relapse was 22 months (range, 0-39.9) and 58 months (range, 30.9-140.6), respectively (P= 0.096). Conclusions: Our anecdotal experience reflects the feasibility of stopping TKI in a subset of pts with Ph+ ALL and sustained molecular remissions. Longer follow up and validation of these findings on a larger cohort are highly needed before attempting to discontinue TKI. Disclosures Kantarjian: Astex: Research Funding; Ariad: Research Funding; Jazz Pharma: Research Funding; AbbVie: Honoraria, Research Funding; Cyclacel: Research Funding; Immunogen: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Takeda: Honoraria; Agios: Honoraria, Research Funding; Novartis: Research Funding; Amgen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Daiichi-Sankyo: Research Funding. Sasaki:Otsuka: Honoraria; Pfizer: Consultancy. Konopleva:Ascentage: Research Funding; Reata Pharmaceuticals: Equity Ownership, Patents & Royalties; Agios: Research Funding; Ablynx: Research Funding; Cellectis: Research Funding; Amgen: Consultancy, Honoraria; F. Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Calithera: Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding; Forty-Seven: Consultancy, Honoraria; Eli Lilly: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Kisoji: Consultancy, Honoraria; Astra Zeneca: Research Funding; Genentech: Honoraria, Research Funding. O'Brien:Acerta: Research Funding; AbbVie: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Sunesis: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Kite: Research Funding; GlaxoSmithKline: Consultancy; Gilead: Consultancy, Research Funding; Eisai: Consultancy; Celgene: Consultancy; Astellas: Consultancy; Aptose Biosciences, Inc: Consultancy; Amgen: Consultancy; Alexion: Consultancy; TG Therapeutics: Consultancy, Research Funding; Vaniam Group LLC: Consultancy; Verastem: Consultancy; Regeneron: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding. Kadia:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bioline RX: Research Funding; BMS: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Research Funding. Jabbour:Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Cyclacel LTD: Research Funding.

PURPOSE: Cdk4 inhibitors (CDK4i), such as palbociclib, are approved in combination with hormonal therapy as a front line treatment for metastatic HR+, Her2- breast cancer. However, despite these advances, many patients demonstrate either de novo or acquired resistance. This highlights the need to identify biomarkers to pinpoint patients who would respond to this therapy. In Rb+ tumors, which comprise the majority of HR+ breast cancers, Ki67, Cyclin D, cdk4, and p16 levels do not identify responsive subgroups. Cyclin D or cdk4 levels themselves are not reliable because tyrosine phosphorylated p27Kip1 (pY88) is required for activation of the cyclin D-cdk4 (DK4) complex. We have previously shown that the level of pY88 correlates with cdk4 activity: the more pY88 detected, the greater the specific activity of cdk4 (Patel, et. al. MCR, 2018). We developed dual immunohistochemical staining for p27 and pY88 and demonstrated that pY88 status, which is negative in benign breast epithelium, stratified tumors across all hormone receptor groups (Gottesman, et.al, MCR, 2018). Lack of pY88 suggested that DK4 was inactive, and that these samples would not have the active cdk4 target. We have grown tumor resection material in explant culture, treated with palbociclib, and stained with Ki67 as a marker of response. Explants from the no pY88 group were non-responsive, while explants from the low or high pY88 group responded to drug. Thus, we hypothesized the pY88-p27 status may serve as a biomarker for patients that can respond to cdk4i therapy. RESULTS: We analyzed paraffin-embedded archival breast cancer biopsies from a 13 patient cohort of HR+, Her2- patients who had received Palbociclib/Letrozole in the front line metastatic setting. 62% of these patients progressed within 8 months of treatment, while 38% were on drug for 12-38 months. Using our staining method, we stratified patients into three groups based on pY88 status: 23% had no staining (Group 0), 38% had a low percentage of pY88+ cells (Group 1), and 38% had a high percentage of pY88+ cells (Group 2, >30% of cells pY88+). We then compared the time until disease progression, when they were removed from drug, for each group. Patients with a pY88 score of 0 had disease progression within 6-8 months, suggesting that they exhibited primary resistance. Patients with a pY88 score of 2 also showed disease progression within 6 months. This suggested that the Y88 high group may have too much active cdk4 target to respond to pharmacological drug dose, a hypothesis supported by our breast cancer cell line data. However, patients with a low pY88 score were all still on drug after 12+ months with either reduced tumor or stable disease. Additional patients continue to be recruited. CONCLUSION: Our data suggest that pY88-p27 status, as a surrogate marker for cdk4 activity, associates with responsiveness to CDK4i treatment. Clinical use of the pY88 biomarker may identify patients responsive or resistant to Cdk4 targeting drugs. Citation Format: Stacy W. Blain, Susan R.S. Gottesman, Jonathan Somma, Vladislav Tsiperson, Julia McGuinness, Matthew Ingham, Kevin Kalinsky, Gary Schwartz, Elina Tress, Hanina Hibshoosh, Mohamed Mh Kahila, Bachar Samra Samra, Evelyn Taiwo, Steve Xie. Tyrosine phosphorylation of p27Kip1 associates with Palbociclib responsiveness in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-224.

Advanced non-small cell lung cancer (NSCLC) has been conventionally treated with cytotoxic chemotherapy with short-lived responses and significant toxicities. Monoclonal antibodies to programmed death-1 receptor (PD-1) and programmed death ligand 1 (PD-L1) have shown tremendous promise in the treatment of advanced NSCLC in various clinical trials. Areas covered: In this article, we will review the outcomes of various trials of anti-PD-1/anti-PD-L1 antibodies in the treatment of NSCLC. We will also discuss their mechanism of action and toxicities. Expert commentary: Anti-PD-1/PD-L1 antibodies offer several advantages including significant antitumor activity, induction of long lasting responses, and favorable safety profile. Several trials are now being conducted to evaluate their efficacy as first line agents as well as in combination with other agents. More research is also needed to identify other biomarkers, in addition to PD-L1 expression, that could more reliably predict response to these drugs, and aid in better patient selection.

Background: Adult T-Cell Lymphoma/Leukemia (ATLL) is a rare and aggressive HTLV-1 related peripheral T-cell lymphoma that occurs predominantly in Japan and the Caribbean basin. Acute (A) and lymphomatous (L) subtypes are the most aggressive forms with a median overall survival (OS) of 6-12 months despite chemotherapy. Typical immunophenotype (IP) of ATLL is CD4+/CD8- with strong co-expression of CD25. Atypical IP has been reported in ~10-20% of cases, and has been linked to a more aggressive disease in rare Japanese case reports. However, little literature exists on the Caribbean population. Kings County Hospital (KCH) and University Hospital of Brooklyn (UHB) serve a big Caribbean community in Brooklyn, New York. Our primary objective is to describe the clinicopathologic characteristics and treatment outcomes of our Caribbean patients. We also aim to evaluate the effect of IP on prognosis. Methods: We conducted a retrospective analysis of all patients diagnosed with HLTV1+ ATLL at KCH and UHB between 2005 and 2017. Diagnosis of ATLL was established based on clinical history, pathological findings and HTLV1 serum positivity. We included patients with A and L subtypes only. IP was based on flow cytometry from peripheral blood and/or immunostaining from lymph node biopsy. For the univariate analysis, outcomes were calculated using the log-rank test, and survival curves were estimated by Kaplan-Meier method. Results: We identified 63 patients with A and L subtypes. The median age was 54 with female predominance (65%). A and L subtypes were noted in 55% and 45% of patients respectively, and 95% had Ann Arbor stage III/IV. Two patients transformed to A subtype from chronic disease, and one patient transformed to L subtype from smoldering disease. Organ involvement at presentation was as follows: lymphadenopathy (80%), bone marrow (63%), hepatomegaly (25%), skin lesions (24%), bone lesions (23%), splenomegaly (21%), pleural effusions (14%), lung (11%), and CNS (8%). Hypercalcemia was noted in 47%, and only 4 patients had normal LDH. Out of 26 patients with a reported karyotype, 8 patients had abnormal cytogenetics (31%). Most patients received upfront EPOCH (78%) or CHOP chemotherapy (14%). The objective response rate (ORR) was 47% (complete response [CR] 16%, partial response [PR] 31%) and stable disease (SD) was achieved in 14%. None of the patients received antiviral therapy or consolidative stem cell transplant. The median duration of response was 2.1 months. The median OS was 5.8 months and median progression-free survival (PFS) was 4 months. Strikingly, 4 patients survived beyond 3 years including two who remain alive at 5+ years without further therapy. Of patients with relapsed/refractory (R/R) disease (85%), 35 patients (66%) received 2nd line treatment (mostly ICE chemotherapy: 27%). ORR was 21% (1 CR and 6 PR) and another patient had SD. For R/R patients, the median OS was 2.2 months and median PFS was 2 months. Univariate analysis showed that the following factors were associated with shorter OS and PFS: LDH > twice the upper limit of normal (p=0.002 and 13 mg/dl (p Conclusion: Our large cohort of Caribbean patients with acute and lymphomatous subtypes of ATLL suggests a chemo-refractory and more aggressive disease compared with Japanese population, highlighting the need for novel therapies. In our patient population, incidence of atypical immunophenotype was higher than previously reported and was associated with worse PFS and OS. Disclosures: No relevant conflicts of interests to declare. Disclosures No relevant conflicts of interest to declare.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and severe clinical syndrome characterized by a dysregulated hyperinflammatory immune response. The diagnosis of HLH during pregnancy is especially challenging due to the rarity of this condition. The highly variable clinical presentation, laboratory findings, and associated diagnoses accompanying this syndrome further complicate the problem. A pronounced hyperferritinemia in the setting of systemic signs and symptoms along with a negative infectious and rheumatological workup should raise suspicions for HLH. While treatment ideally consists of immunosuppressive chemotherapy and hematopoietic stem cell transplant, the potential toxicity to both the pregnant woman and the fetus poses a challenging decision. We report the first case of idiopathic HLH presenting as fever of unknown origin in a pregnant woman successfully treated with steroids.