Abstract: Very little data exist for the incidence patterns of adult T‐cell leukemia/lymphoma in the United States. Using the National Program of Cancer Registries; Surveillance, Epidemiology, and End Results; and New York State Cancer Registry databases, this is the largest comprehensive epidemiological study of adult T‐cell leukemia/lymphoma in the United States, and it shows a rising incidence with a younger age at presentation and poor overall survival for non‐Hispanic blacks.

Abstract: 8047 Background: In 2014, the definition of multiple myeloma was updated to include serum free light chain (FLC) ratio ≥100 as a myeloma defining biomarker, based on retrospective data indicating a 2-year progression rate of 80% and a median time to progression (TTP) of 12 months associated with this marker. However, two recent studies have reported lower 2-year progression rates, 30-44%, and longer median TTP of 40 months in patients with FLC ratio ≥100. Because of the disparity in risk prediction by FLC ratio across studies, we were motivated to assess the risk of progression in patients with SMM and a FLC ratio ≥100. Methods: We performed a retrospective analysis of patients diagnosed with SMM at Memorial Sloan Kettering Cancer Center between January 2000 and December 2017. Diagnosis of SMM and progression to MM was defined according to the International Myeloma Working Group (IMWG) criteria at the time of diagnosis. Kaplan-Meier method was used to assess TTP and generate survival curves, with log-rank test for comparison between groups. Results: A total of 438 patients were included in the study, with a median follow-up time of 52 months. While all patients with a FLC ratio ≥100 (n = 66) had elevated involved FLC levels, 35 (53%) had an involved FLC concentration 〉 100 mg/L. Per current diagnostic criteria, we only included patients with an involved FLC concentration 〉 100 mg/L in the FLC ratio ≥100 group, and found a median TTP of 31 months (95% confidence interval [CI] 16-59 months) and a 2-year progression rate of 49% (CI 28-63%). In a sensitivity analysis including all 66 cases with FLC ratio ≥100 (independent of involved FLC concentration), we found the median TTP to be 41 months (CI 30-72 months), compared to 101 months for those with a FLC ratio 〈 100 (CI 78-127 months; p 〈 0.0001). The risk of progression within 2 years was 35% (CI 22-46%) compared to 18% (CI 14-23%; p 〈 0.0001). Of note, 22 patients with a FLC ratio ≥100 were monitored expectantly for 〉 4 years, among whom 12 patients had an involved FLC level 〉 100 mg/L. Ten patients (7 with involved FLC level 〉 100 mg/L) were followed over a period ranging from 4 to 8.5 years before eventually progressing, and 12 patients (5 with involved FLC level 〉 100 mg/L) were followed between 4 and 8 years and did not progress during the study period. Conclusions: While FLC ratio ≥100 is associated with a high risk of progression in patients with SMM, it does not infer an imminent risk of progression, defined by the IMWG as median TTP of 12 months and 2-year progression rate of at least 80%. On the contrary, select patients with FLC ratio ≥100 can be followed for many years without progressing and some may never progress despite long-term follow-up. These findings suggest that in patients where FLC ratio ≥100 is the only myeloma-defining event, other high-risk features as well as the evolution of FLCs over time should be considered in the decision to start a patient on treatment.

Abstract: Introduction: Autologous stem-cell transplant (ASCT) is standard-of-care for the treatment of multiple myeloma (MM), but most patients eventually relapse. Patients with early relapse, within 12-24 months of ASCT, have a lower overall survival that is not fully explained by conventional high-risk disease features, such as frailty, extramedullary disease, and cytogenetics. In this study, we performed high-dimensional flow cytometry-based immune phenotyping of the T-cell compartment of MM patients to identify features predictive of early relapse. Methods: Peripheral blood samples collected at 90 days post-ASCT from participants in BMT CTN 0702 comprised two cohorts: an early relapse cohort (ER), defined as relapse within 24 months from ASCT, and a long-term responder cohort (LR) defined as not relapsed at & gt;4 years from ASCT. We performed 28-color flow cytometry to explore differences in T-cell subset frequency and activation state between cohorts. A total of 96 patients from the ER (n=51) and LR (n=45) cohorts were analyzed. We manually gated on live, CD3+ events and integrated all patient samples. High-dimensional flow cytometry analysis was conducted using the FlowSOM algorithm, which identified 20 cell clusters. We manually annotated each cluster based on CD45RA and CCR7 expression into separate CD4 and CD8 effector and memory subsets. Differential expression analysis was performed with empirical Bayesian testing, controlling for batch effect and treatment modality, followed by effect size estimates with Cohen's d. Results: We observed 2 out of 20 cell clusters with a significant difference in proportion between groups. For ER patients, there were two CD45RA -, CCR7 +, CD25 +, CCR4 + CD4 + clusters with a 29% (log fold change (LFC) = -0.628, p-value & lt; 0.001) and 54% relative decrease in cell number (LFC = -1.25, p-value & lt; 0.001), suggesting an absence of activated central memory CD4 T cells with early relapse. Analysis of positive and negative costimulatory molecules revealed upregulation of PD1, CD38, and TIGIT, with corresponding decreased expression of granzyme B, CD28, and CD27 within multiple CD4 and CD8 clusters among the ER group (Figure 1A). By differential expression testing, early relapse was most strongly associated with CD28 downregulation by effector memory (CD45RA -, CCR7 -) CD8 T cells (LFC = -0.016, p-value & lt; 0.001), increased PD1 expression by effector memory CD8 T cells (LFC = 0.022, p-value & lt; 0.001), increased TIGIT expression by central memory (CD45RA -, CCR7 +) CD8 T cells (LFC = 0.038, p-value & lt; 0.001), and decreased granzyme B among T regulatory (FoxP3 +, CD25 +) cells (LFC = -0.030, p-value & lt; 0.001) (Figure 1B). Conclusion: Distinct signatures of T-cell exhaustion and depletion are present in the early post-ASCT period among individuals relapsing within 24 months. Peripheral blood immune phenotyping may identify functionally high-risk patient populations in need of alternative treatment approaches to maintain durable disease control.

Abstract: Adult T cell leukemia / lymphoma is a rare neoplasm with dismal cure rates and poor response to chemotherapy. The genetic basis of refractoriness against conventional agents is not known. We follow one of the largest cohorts of ATLL in the US and recently showed that North American ATLL (NA-ATLL) has a distinct mutational profile from Japanese ATLL (J-ATLL) with a higher incidence of epigenetic mutations (Shah et al, Blood, 2018; 132(14):1507-1518). Here, we analyze the mutational landscape of ATLL clones at diagnosis and at relapse in a pilot study of 7 NA-ATLL patients using deep targeted sequencing of 236 recurrently mutated genes. Our goal was to examine clonal evolution patterns that may result as a consequence of the selective pressure of chemotherapy by determining changes in mutational profiles as well as clonal abundance on patients with aggressive ATLL [acute and lymphomatous] (Table 1). All patients were treated with EPOCH (Etoposide, Prednisone, Vincristine, Cyclophosphamide and Doxorubicin) chemotherapy after initial diagnosis except one patient who received interferon therapy. Distinct patterns of clonal evolution were observed in patients with primary refractory disease when compared to those who relapsed after an initial remission. Group 1 has 3 cases (Pts 1 to 3), all of which experienced early relapse and showed mutation patterns suggestive of clonal replacement by a new emerging clone at relapse. Group 2 has 3 patients (Pts 4-6) that are characterized by worsening of primary refractory disease. Mutation patterns in the before-and-after sample pairs suggest linear progression from a previously existing clone during therapy. The clonal evolution status was not resolved in our third group (Pt#7) indicating that mutations outside the 236 genes evaluated might have been present. Frequent epigenetic mutations were found in both diagnostic and refractory/relapsed samples. Surprisingly, 4 epigenetic mutations (KMT2D, EP300, SPEN, SETBP1) identified in 4 cases were confirmed or suspected of germline origin. This suggests that ancestral genomic differences between the Caribbean and Japanese populations could contribute to the mutational and clinical disparities between NA- and J-ATLL. Multiple mutations with similar variant allele frequencies (VAF) at the time of relapse were identified, suggesting simultaneous acquisition of several mutations during clonal evolution. Clonal replacement by an emerging clone (Group 1) such as GATA3 (Pt#3) or KMT2D (Pt#1) (either germline or founding mutation) was observed in patients who achieved an initial response. On the other hand, in primary refractory disease (Group 2), relapse was driven by dominant TBL1XR1 mutations in 2 out of the 3 cases either alone (Pt#6) or in combination with mutated SMARCB1 (Pt#5). The protein encoded by TBL1XR1 is a negative regulator of the nuclear receptor corepressor (NCoR) /histone deacetylase 3 (HDAC3) complex. Therefore, TBL1XR1 inactivation is expected to result in hyper-activity of NCoR/HDAC3, an epigenetic abnormality targetable by HDAC inhibitors. SMARCB1 is also an epigenetic regulator associated with several malignancies and has been targeted with alisertib. A subclonal expansion of EP300 (a histone acetyltransferase) appears to drive relapse in the other case of this group (Pt#4). Therefore, our primary refractory cases show that epigenetic mutations seem to be of utmost importance not only at diagnosis as we have previously shown, but as the driving force behind chemotherapy refractoriness and subsequent relapse. Conclusion: To our knowledge, this is the first mutation-based clonal evolution study aimed to examine dynamic changes induced by chemotherapy among NA-ATLL patients. Early relapse appears to be driven by the emergence of new mutant clones. On the other hand, primary refractory disease appears to have epigenetic drivers that convey chemotherapy refractoriness and evolve from linear progression of a previously existing clone. Serial mutational testing can provide critical information on clonal architecture and identify actionable molecular vulnerabilities in a cohort without effective therapeutic options and a dismal prognosis. Disclosures Sica: Physician's Education Resource (PER): Honoraria. Shah:Physicians' Education Resource: Honoraria. Steidl:Aileron Therapeutics: Consultancy, Research Funding; Stelexis Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Scientific Co-Founder; Pieries Pharmaceuticals: Consultancy; BayerHealthcare: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; GlaxoSmithKline: Research Funding; Celgene: Consultancy. Verma:Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria; Celgene: Honoraria; BMS: Research Funding; Janssen: Research Funding.

Abstract: Introduction Adult T-cell leukemia/lymphoma (ATLL) is a rare, aggressive T cell neoplasm associated with a retrovirus human T cell lymphotropic virus (HTLV-1) and carries a dismal prognosis. Within the United States, New York, and Florida see the majority of cases due to the concentration of Caribbean immigrants (Zell, Assal et al. 2016, Malpica, Pimentel et al. 2018). SEER data does not include states like New York and Florida where most cases are seen and therefore a true estimate of the disease burden in this country is not known (Chihara, Ito et al. 2012, Adams, Newcomb et al. 2016). Aim We aim to study the epidemiology and clinical outcomes of ATLL in the United States particularly in the state of New York. Methods Data for New York was obtained from the New York State Cancer Registry (NYSCR). Data were also retrieved from 18 Surveillance, Epidemiology, and End Results (SEER) registries in the United States. Patients with ATLL (HTLV-1 positive) (includes all variants) were categorized using the International Classification of Diseases for Oncology, Third Edition codes ICD-O-3 as 9827/3. Race/ethnicity was categorized as non-Hispanic white, non-Hispanic black, all Hispanic and other/unknown in the NYSCR whereas it was categorized as non-Hispanic white, non-Hispanic black, all Hispanic, non-Hispanic American Indian/Alaska Native, non-Hispanic Asian or Pacific Islander, and non-Hispanic unknown race in SEER. ATLL patients ≥ 15 years of age were identified from 1995 to 2014 in SEER and all ages were included in NYSCR. Survival was estimated from SEER follow-up data with Kaplan Meier survival analysis. For NYSCR mean and median survival time (month) for deceased patients - cases diagnosed through death certificate only were removed. NYSCR does not conduct active patient follow-up and assumes patients are still alive if we didn't find a deathmatch through vital record or National Death Index linkages. Results Five hundred and eleven patients with ATLL were identified in SEER. These patients had a median survival of 8 months (m) which was worse than all other subtypes of peripheral T cell lymphoma. (Figure 1) Four hundred and twenty-nine patients with ATLL were identified in NYSCR and these patients had a median survival of 4.5 m. (Figure 2) Over the years from 2000 until 2014 the number of cases diagnosed within SEER registry coverage areas has not changed. In New York state however there has been a doubling in the number of cases diagnosed from 1995 to 2014. (Figure 3A, B) The non-Hispanic black population was diagnosed at a median age of 52.5 in SEER and 54 in NYSCR while the non-Hispanic whites were diagnosed at a median age of 71 in SEER and 64.5 in NYSCR. The Hispanic patients were diagnosed at a median age of 58.5 in NYSCR and 52.5 in SEER. (Figure 4A, B) There was no gender predominance with 50% males in both registries. ATLL patients in SEER were 47.2% non-Hispanic white, 31.7% non-Hispanic black, 9.8% Hispanic and 11.4% other/unknown. There were 5.5% Japanese patients (n=28) diagnosed in SEER. NYSCR had 22.4% non-Hispanic white, 59.4% non-Hispanic black, 15.9% Hispanic and 2.3% other/unknown. (Figure 5A, B) Within SEER registries most cases occurred in New Jersey, California, Connecticut and Georgia. (Figure 6) New York state had a significantly higher number of cases than these states. Seventy four percent cases diagnosed within New York state are diagnosed in New York city and only 26% of cases are diagnosed in upstate New York. Based on reported country of birth within New York state, only 27% of the ATLL cases diagnosed are born in the US whereas 49% are born in the Caribbean (most likely to be from Jamaica, Dominican Republic and Haiti). (Figure 7A, B, C) For SEER and NYSCR the age-adjusted cancer incidence rate by race year and other factors will be presented at the meeting. Conclusions ATLL has a worse prognosis than all other PTCL subtypes. New York State has a high endemicity for ATLL with a rising number of cases. The higher percentage of non-Hispanic black patients in New York compared to the rest of the country is consistent with the diverse racial demographics in this state. Survival varied significantly by race/ethnicity and disparities were evident especially for non-Hispanic blacks who were diagnosed at a younger median age and had a shorter survival. Further research into this aggressive disease is needed to improve outcomes for these patients. Disclosures No relevant conflicts of interest to declare.

Abstract: Introduction The current standard to assess chemotherapy tolerability and health related quality of life (HRQOL) relies on patient (PT) self-reporting. Continuous passive monitoring using mobile wearable devices can objectively aggregate and monitor "activity" over long periods of time without potential reporting bias. Due to the nature of the disease, multiple myeloma (MM) PTs are often ridden with bone disease and pain, thereby limiting activity while impacting HRQOL. In this prospective clinical study, we enrolled 40 newly diagnosed MM PTs and remotely monitored their activity (steps/24 hrs) while administering electronic PT reported outcome (ePRO) surveys at baseline (BL) and through induction therapy. The study aim was to assess whether wearables can establish patterns of physical activity while receiving therapy and how these activity bioprofiles correlate with HRQOL outcomes. Methods PTs were eligible for the study if they had newly diagnosed MM, not having received any systemic therapy, and if they owned a device (iOS or Android) compatible with Garmin Vivofit® (GV) device. Regimens were determined by treating physicians. PTs were given GV® devices and asked to download a GV® application and Medidata ePRO app. PTs were assigned to either Cohort A - PTs & lt;65 years or Cohort B - PTs ≥ 65 years. PTs were remotely monitored for physical activity and sleep at BL (1-7 days prior to therapy) and continuously up to 6 cycles of therapy. Additionally, PTs completed ePRO surveys [(EORTC - QLQC30 and MY20) at BL and after each cycle. Activity data and completed ePRO surveys were synced to Medidata Rave through Medidata Sensorlink technology. Responses at the end of cycle 6 were scored by IMWG response categories: & gt; VGPR Responders (Res) vs. & lt; PR Sub-responders (Sub-Res). Associations between physical activity measurements, QLQC30 and MY20 scores, and time from the start of treatment were estimated using a linear mixed model with a random intercept. A Wald-test was used to compute p-values for the significance of association. Results Between Feb 2017 and Sep 2019, 40 PTs (21 M and 19 F) were enrolled with 20 in cohort A (mean 54 yrs, 41-64) and 20 in cohort B (mean 71 yrs, 65-82). Treatment regimens included KRd 14(35%), RVd 12(30%), Dara-KRd 8(20%), VCd 5(12.5%), and Rd 1(2.5%). Activity bioprofiles were compiled among 24/40(60%) PTs: 14 full sets (7/7 cycle periods) and 10 partial sets [1 PT - 2/7(28.5%) cycle periods; 2 PTs - 3/7(42.8%); 1 PT - 4/7(57.1%); 2 PTs- 5/7(71.4%); 4 PTs 6/7(85.7%)]. PT activity increased over time by 179 steps/24 hrs per cycle (p=0.001, 95% CI: 68-289) for the entire study. Mean activity pre- vs. post- for cohort A was 6,041 vs. 7,266 steps/24 hrs, respectively with an increase of 116 steps/24 hrs per cycle (p=0.2, 95% CI: -60-293), and for cohort B 2,984 steps/24 hrs vs. 5,007 steps/24 hrs with an increase of 260 steps/24 hrs per cycle (p & lt;0.001, 95% CI: 154-366) (fig 1). There was improvement in activity levels in both Res 169 steps/24 hrs per cycle (p= 0.02, 95% CI: -31-305) and Sub-Res 212 steps/24 hrs per cycle (p= 0.01, 95% CI: 53-371) groups. PTs reported improvement in ePRO MY20 disease burden symptoms over time, -1.6 score/cycle (p=0.001, 95% CI -2.6- -0.6). There was no observed change in time over self-body image (p=0.5), while PTs reported worsening of future perspective, -2.8 score/cycle (p & lt;0.001, 95% CI -2.6- -0.6). Similarly, there was an observed improvement of QLQC30 global health status, + 1.7 score/cycle (p=0.02, 95% CI: 0.3-3.1) and physical functioning over time +2.1 score/cycle (p & lt;0.001, 95% CI: 1.2-3.0). An association between increased PT activity (steps/24 hrs) and decreased symptom burden was observed (p=0.04). Increased PT activity was also associated with improved global health status (p=0.02) and physical functioning (p & lt;0.001) scores. Conclusion Our study demonstrates that passive wearable monitoring can successfully capture PT activity in newly diagnosed MM, and that PT activity bioprofiles correlate well with traditional HRQOL measurements. Of clinical relevance, our study shows that activity bioprofiles improve with therapy, regardless of depth of response. Significant gains in activity were attributable to the older cohort, suggesting a greater functional impact at BL in this population. Future studies are needed to elucidate how mobile wearables may aid the clinician in passive monitoring of therapy tolerability in the outpatient setting. Figure 1 Disclosures Korde: Amgen: Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees. Mailankody:PleXus Communications: Honoraria; Juno Therapeutics, a Bristol-Myers Squibb Company: Research Funding; Allogene Therapeutics: Research Funding; Janssen Oncology: Research Funding; Takeda Oncology: Research Funding; Physician Education Resource: Honoraria. Hassoun:Novartis: Consultancy; Celgene: Research Funding; Takeda: Research Funding. Lesokhin:Takeda: Consultancy, Honoraria; GenMab: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; BMS: Consultancy, Honoraria, Research Funding; Janssen: Research Funding; Juno: Consultancy, Honoraria; Genentech: Research Funding. Lendvai:Janssen: Current Employment. Smith:Bristol Myers Squibb: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics: Consultancy; Precision Biosciences: Consultancy. Hultcrantz:Daiichi Sankyo: Research Funding; GSK: Research Funding; Intellisphere LLC: Consultancy; Amgen: Research Funding. Shah:Physicians Education Resource: Honoraria; Celgene/BMS: Research Funding. Shah:Amgen: Research Funding; Janssen Pharmaceutica: Research Funding. Giralt:Jazz: Research Funding; Kite: Research Funding; Actinuum: Research Funding; CSL Behring: Research Funding; Pfizer: Research Funding; Quintiles: Research Funding; Janssen: Research Funding; Amgen: Research Funding; Sanofi: Research Funding; Celgene: Research Funding; Adienne: Research Funding. Landgren:Adaptive: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Glenmark: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Karyopharma: Research Funding; Binding Site: Consultancy, Honoraria; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; BMS: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; Glenmark: Consultancy, Honoraria, Research Funding; Juno: Consultancy, Honoraria; Seattle Genetics: Research Funding; Pfizer: Consultancy, Honoraria; Merck: Other; Karyopharma: Research Funding; Binding Site: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Merck: Other.

Abstract: Background. Prior studies consistently show that the use of maintenance therapy after completion of combination therapy translates into longer progression-free survival (PFS) in patients with multiple myeloma. Some studies show that maintenance therapy prolongs overall survival (OS). Typically, maintenance therapy is used in the setting of newly diagnosed multiple myeloma; however, emerging data suggest that (at least a subset of) patients in the early relapse setting, for example those who achieve MRD negativity, may also be candidates for maintenance therapy integrated with careful disease monitoring. Currently, lenalidomide is considered the standard of care for maintenance; however, there is only limited published data on long-term use, with respect to the ability to sustain MRD negativity, mechanisms of relapse, and late toxicities. We were motivated to develop a study focusing on long-term lenalidomide maintenance therapy and to study clinical and correlative data. Here, we report on sustained MRD negativity and clinical tolerability. Methods. This single arm, phase 2 was designed to enroll 100 evaluable patients. Per protocol, maintenance therapy with lenalidomide 10 mg is given days 1-21 on a 28-day cycle. The initial study design had a total duration of 36 months; it was subsequently extended with additional 24 months (i.e., total of 60 months). Per standard procedures for protocol amendments, patients were offered to re-consent for the extension. Per protocol, patients underwent bone marrow biopsies and aspirates as well as PET/CT exams at baseline, annually, at progression/end of treatment; blood work was done every 3 months. Bone marrow and blood samples were banked longitudinally per the research protocols. Based on practical considerations, the study was statistically powered for the primary end-point progression-free survival, which provided sufficient numbers of samples for the planned correlative assays focusing on MRD testing, genomic characterization of detectable disease, and profiling of the bone marrow microenvironment. All these assays were conducted in serial samples collected over time and assessed in relation to clinical outcomes. Results. A total of 100 evaluable patients meeting eligibility criteria were enrolled (63% males) between September 2015 and January 2019. Baseline characteristics include median age 63 years (range 38-86 years) and median ECOG score 1 (range 0-1). At the submission of this abstract, the median number of cycles delivered is currently 26 (range 1 to 48); 86 patients have completed 12 or more cycles, 57 patients have completed 24 or more cycles, and 29 patients have completed 36 or more cycles. MRD testing had been completed at least once in all patients. Thirty-four patients were MRD negative at enrollment. At median followup time of 28 months (range 3.4 to 45.6), 15/100 (15%) patients have progressed. Considering the entire follow-up time from initial MRD negativity to last follow-up on study, we found 39 (of 85 tested; 46%) and 25 (of 57 tested; 44%) to have evidence of 1 and 2 years sustained MRD negativity, respectively. Only 19 patients were tested for MRD at 3 years and 16 (84%) had sustained MRD negativity. Toxicities (grade 3) include neutrophil count decrease (N=9), hypertension (N=3), diarrhea (N=2), lung infection (N=2), and rash maculo-papular (N=2), and toxicities (grade 4) include sepsis (N=2) and platelet count decrease (N=1). The most common 1/2 toxicities were diarrhea (N=51), fatigue (N=33), and upper respiratory infection (N=23). Among evaluable patients, dose reductions of lenalidomide due to toxicities and tolerability issues were done in 6 (6%) patient. Conclusions. Among evaluable patients who were treated with lenalidomide 10 mg maintenance therapy days 1-21 on a 28-day cycle on this study, at a median followup of 28 months, we found 46% and 44% to have evidence of 1 and 2 years sustained MRD negativity, respectively. Currently, 19 patients have been tested for MRD at 3 years; 16 (84%) show evidence of 3 years sustained MRD negativity. The toxicity profile was in accord with prior studies and tolerability was quite good reflected in only 6 patients requiring dose reductions due to toxicities. Correlative assays focusing on mechanisms of sustained MRD negativity in this study are presented in a separate abstract at this meeting. Disclosures Landgren: Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Theradex: Other: IDMC; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Other: IDMC. Lesokhin:Genentech: Research Funding; GenMab: Consultancy, Honoraria; Janssen: Research Funding; Serametrix Inc.: Patents & Royalties; Juno: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria. Smith:Celgene: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics and Precision Biosciences: Consultancy. Mailankody:Juno: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Takeda Oncology: Research Funding; CME activity by Physician Education Resource: Honoraria. Hassoun:Janssen: Research Funding; Celgene: Research Funding; Novartis: Consultancy. Landau:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; Prothena: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Scordo:Angiocrine Bioscience, Inc.: Consultancy; McKinsey & Company: Consultancy. Arcila:Invivoscribe, Inc.: Consultancy, Honoraria. Ho:Invivoscribe, Inc.: Honoraria. Roshal:Physicians' Education Resource: Other: Provision of services; Celgene: Other: Provision of Services; Auron Therapeutics: Equity Ownership, Other: Provision of services. Dogan:Roche: Consultancy, Research Funding; Corvus Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Novartis: Consultancy.

Abstract: e19070 Background: Peripheral T-cell lymphomas (PTCL) are a rare heterogenous group of lymphomas and modern studies on incidence patterns of PTCL are lacking. Methods: Using the National Program of Cancer registries (NPCR) database, which covers 99% of the US population, we aim to evaluate the incidence of PTCL according to age, race-ethnicity, and gender; and examine trends over time. We identified PTCL using ICD-O-3 codes and evaluated incidence trends from 2001 to 2015. Results: A total of 78722 PTCL cases were identified, the most common were Mycoses fungoides/Sezary syndrome (MF-SS), PTCL Not Otherwise Specified (NOS), and ALK+ Anaplastic Large Cell Lymphoma (ALK+ ALCL). The age-adjusted incidence rate was 2.1 per 100,000. Incidence of PTCL increased with age (6.7/100,000 in 80+years). PTCL was more common in males than females (incidence rate ratio [IRR] of 0.6, p 〈 0.05). Most PTCL were more common in Non-Hispanic Blacks (NHB). Incidence rates of MF-SS, PTCL NOS, Hepatosplenic TCL (HSL) in NHB were 0.8, 0.8, and 0.02 per 100,000 [IRR 1.7, 1.8, 2.2, p 〈 0.05] respectively which is approximately twice that of Non-Hispanic whites (NHW). Viral related PTCL like Adult T-cell Leukemia Lymphoma (HTLV), Angio-Immunoblastic T-cell Lymphoma [AITL] (EBV), Extranodal NK-TCL nasal type [ENK TCL] (EBV), NK cell leukemia (EBV) are higher in groups at highest predisposition such as NHB and Non-Hispanic Asian Pacific Islanders (NHAPI). Primary cutaneous (PC) gamma-delta TCL occurs exclusively in NHW at an incidence rate of 0.03 per 100,000. There was no increase in overall yearly incidence of PTCL over the study period (0.1%, p=NS) but the incidence increased in NHB (Annual Percent Change [APC] 1.4%, p 〈 0.05). Incidence of ENK TCL and AITL increased in NHAPI (2.2% and 3.7%, respectively [p 〈 0.05]). The incidence of ALK + ALCL, PC CD30+ TCL decreased (APC -4.2%, -2% [p≤0.05] respectively). Conclusions: This is the first study to show unique incidence patterns of PTCL namely higher incidence in males, African Americans (esp. MF, PTCL-NOS and HSL unaccounted for viral etiologies) and exclusivity of primary cutaneous gamma delta TCL in NHW. Further research is needed to understand these differences.

Abstract: 8063 Background: Information on central nervous system (CNS) involvement with NA-ATLL is limited. In this study, we describe CNS involvement in ATLL patients at a tertiary hospital in New York City. Methods: We considered CNS involvement if one of the following criteria was met 1) cerebrospinal fluid (CSF) cytology or flow cytometry was positive 2) CNS imaging was positive for disease involvement or 3) Physical exam findings were compatible with neurologic involvement. Results: Of 94 NA-ATLL patients, 21 (22.3%) had CNS involvement by ATLL. CSF was involved in 13/21 and 5/21 patients at diagnosis and relapse respectively. At diagnosis, MRI showed CNS involvement in brain and spine in 5/21 (24%) and 3/ 21 (14%) cases respectively. At relapse, imaging revealed brain and spine involvement in 2 patients each. Neurological exam was abnormal in 7 (33%) and 3 (14%) cases at diagnosis and relapse respectively. Next generation exon targeted sequencing was performed in 9 cases. Table shows the mutations (mtn) and functional groups with frequencies. XPO1 E571K mutation was present in 2 patients with extensive CNS disease and refractory to conventional treatment with an overall survival (OS) of 2 months. To our knowledge, this is the first time that XPO1 E571K is reported in a T-Cell malignancy. We also describe here a second set of mutations with CNS involvement (KLF2 and PI3KCD) in 2 patients. Median OS was 8.5 months, Median RFS was 6.5 months in our series. In most cases, the lymphomatous phenotype appeared to have direct mass-like extension (5/21) with several cases of accompanying osteolytic spine or skull lesions, whereas cases with hematogenous involvement tends to spread to the CSF by traversing the brain blood barrier. Conclusions: In this report we describe patterns of CNS involvement in ATLL and the associated mtns. We also describe two unique cases of XPO1E571K mtn in a TCL. [Table: see text]