ABSTRACT
Objectives: Trauma-focused CBT (TF-CBT) has been established as an effective treatment to reduce symptoms of psychological distress including PTSD, anxiety, and depression in parents of preterm infants. The current study compares results of a group-based intervention developed to reduce symptoms of posttraumatic stress with a prior study using an individual version of the treatment manual. Method(s): A total of 26 mothers of preterm infants (25-34 weeks' gestational age;>600 g) received 6 sessions of TF-CBT including psychoeducation, cognitive restructuring, progressive muscle relaxation, and the writing and sharing of their trauma narrative. Outcomes were compared with a group of 62 mothers who participated in a prior RCT with individual therapy based on the same model. Results were also compared for mothers receiving in-person treatment vs telehealth during the COVID-19 pandemic. Result(s): For the entire study period (baseline to follow-up), the individual intervention showed greater improvement in trauma symptoms assessed with Davidson Trauma Scale (d = 0.48;p =.016), although both conditions showed noticeable improvement. Similar patterns were found for maternal depression (Beck Depression Inventory-II [BDI-II]) and anxiety (Beck Anxiety Inventory [BAI]). In-person treatment was found to be superior to telehealth treatment administered during the COVID-19 pandemic, although the difference was not significant. Conclusion(s): Group-based TF-CBT is an effective treatment modality for parents of premature infants with symptoms of psychological distress. However, recruitment of parents was difficult, raising questions about feasibility. Future group-therapy approaches will require a more flexible, open-ended group format in which parents have the option of participating without making a commitment for the full 6-session protocol. Given the national shortage of neonatal intensive care unit (NICU)-based psychological services, group therapy is a potentially viable and cost-effective way to deliver care. PTSD, PAT, P Copyright © 2022
ABSTRACT
Introduction: Patients (pts) with primary refractory or relapsed high-grade lymphoma (HGL) including Burkitt lymphoma (BL) and high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6 (double-hit lymphoma, DHL) have a dismal prognosis with patients almost never achieving a meaningful remission to second line therapy. No standard second line therapeutic approach exists, particularly for BL. The characteristic hallmark of these diseases is a dysregulated MYC oncogene with both downstream effects on proliferation and a high metabolic fluxes which use tricarboxylic acid (TCA) cycle intermediates as biosynthetic precursors. CPI-613 (devimistat) is a non-redox active analogue of lipoic acid, a required cofactor for two key mitochondrial enzymes of the TCA cycle, pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase. Disruption of mitochondrial function by CPI-613 results in a shutdown of ATP and biosynthetic-intermediate production, leading to cancer cell death by apoptosis or necrosis. In the initial phase I trial (n=26) one patient with multiply refractory BL had a partial remission sustained for over one year and then consolidated by surgical resection. She remains alive 7 years later. As of July 2021, 20 clinical studies for various cancers have been conducted (ongoing/completed) with devimistat with over 700 patients having received study drug. We initiated a phase II trial to further explore efficacy in HGL. Devimistat has FDA orphan status for BL and 4 other cancers. Methods: NCT03793140 is a multicenter study aiming to enroll 17 patients on each of two cohorts, BL and DHL, with a Simon's 2-stage design for each cohort, requiring one response among the first 9 treated patients to expand to 17. Patients must have had at least one prior line of therapy or are refusing standard of care and must be more than 3 months after a prior stem cell transplant. Active central nervous system (CNS) parenchymal disease is excluded, but prior leptomeningeal disease is allowed if the CSF is negative for more than 4 weeks at enrollment and maintenance intrathecal therapy is ongoing. Devimistat is given by central line over 2 hours daily x 5 days for two 14-day cycles and then as maintenance x5 days every 21 days. Pts were evaluable for response if they received at least 4 infusions over 5 days of the first cycle. Results: 9 pts were enrolled in the DHL/THL arm. Mediannumber of prior therapies were 3 (range, 1-6). No responses were seen, with only 1 patient achieving stable disease as best response, resulting in cohort closure. Thus far, 8 BL pts were enrolled. Median number of prior therapies was 3 (range, 2-4). Two patients were inevaluable for response. 1/6 patients had stable disease through cycle 7 and one had a complete response (CR). This CR patient (HIV+) with 4 prior therapies entered the study with only a biopsy proven thigh mass. He was not a transplant candidate for social reasons. He had a near complete metabolic remission after 4 cycles of devimistat and a CR after cycle 7. (Table and Figure) As of July 2021, he is in cycle 11, having had a 4-week treatment delay of cycle 5 due to CoVID 19 infection. ECOG improved from 3 to 0. Adverse events (AE): As of July30, 2021, no patient experienced a serious adverse event related to study drug. Four patients had grade 3 events at least possibly related: 2 neutropenia, 1 thrombocytopenia and 1 elevated bilirubin. 1 patient had a dose reduction for grade 2 alanine aminotransferase increase. Conclusions: Although our results are preliminary, the complete remission in this patient is promising in a disease where no viable treatment options exist in the relapsed, refractory BL. Enrollment to the BL cohort is ongoing. [Formula presented] Disclosures: Nikolaenko: Pfizer: Research Funding;Rafael Pharmaceuticals: Research Funding. Pardee: Celgene/BMS: Consultancy, Speakers Bureau;Amgen: Consultancy, Speakers Bureau;Pharmacyclics: Consultancy, Speakers Bureau;Janssen: Consultancy, Speakers Bureau;AbbVie: Membership on an entity's Board of Directors or advisor committees;CBM Biopharma: Membership on an entity's Board of Directors or advisory committees;Karyopharm: Research Funding;Rafael Pharmaceuticals: Research Funding. Abramson: Genentech: Consultancy;Kymera: Consultancy;Karyopharm: Consultancy;AbbVie: Consultancy;Seagen Inc.: Research Funding;Allogene Therapeutics: Consultancy;Astra-Zeneca: Consultancy;Incyte Corporation: Consultancy;BeiGene: Consultancy;Bluebird Bio: Consultancy;Genmab: Consultancy;EMD Serono: Consultancy;Bristol-Myers Squibb Company: Consultancy, Research Funding;C4 Therapeutics: Consultancy;Morphosys: Consultancy;Kite Pharma: Consultancy;Novartis: Consultancy. Horwitz: Vividion Therapeutics: Consultancy;Shoreline Biosciences, Inc.: Consultancy;Tubulis: Consultancy;Verastem: Research Funding;ONO Pharmaceuticals: Consultancy;Myeloid Therapeutics: Consultancy;SecuraBio: Consultancy, Research Funding;Trillium Therapeutics: Consultancy, Research Funding;Seattle Genetics: Consultancy, Research Funding;Millennium /Takeda: Consultancy, Research Funding;Kura Oncology: Consultancy;Janssen: Consultancy;Kyowa Hakko Kirin: Consultancy, Research Funding;Forty Seven, Inc.: Research Funding;Daiichi Sankyo: Research Funding;C4 Therapeutics: Consultancy;Celgene: Research Funding;Aileron: Research Funding;Affimed: Research Funding;Acrotech Biopharma: Consultancy;ADC Therapeutics: Consultancy, Research Funding. Matasar: GlaxoSmithKline: Honoraria, Research Funding;Teva: Consultancy;Janssen: Honoraria, Research Funding;Bayer: Consultancy, Honoraria, Research Funding;Genentech, Inc.: Consultancy, Honoraria, Research Funding;Merck Sharp & Dohme: Current holder of individual stocks in a privately-held company;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding;IGM Biosciences: Research Funding;Merck: Consultancy;Juno Therapeutics: Consultancy;TG Therapeutics: Consultancy, Honoraria;Seattle Genetics: Consultancy, Honoraria, Research Funding;Memorial Sloan Kettering Cancer Center: Current Employment;Pharmacyclics: Honoraria, Research Funding;Daiichi Sankyo: Consultancy;ImmunoVaccine Technologies: Consultancy, Honoraria, Research Funding;Takeda: Consultancy, Honoraria;Rocket Medical: Consultancy, Research Funding. Noy: Rafael Parhma: Research Funding;Morphosys: Consultancy;Targeted Oncology: Consultancy;Medscape: Consultancy;Pharmacyclics: Consultancy, Research Funding;Janssen: Consultancy, Honoraria;Epizyme: Consultancy. OffLabel Disclosure: CPI-613 (devimistat) is a non-redox active analogue of lipoic acid, a required cofactor for two key mitochondrial enzymes of the TCA cycle, pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase. Disruption of mitochondrial function by CPI-613 results in a shutdown of ATP and biosynthetic-intermediate production, leading to cancer cell death by apoptosis or necrosis
ABSTRACT
Introduction: The standard approach for relapsed or refractory (RR) classical Hodgkin lymphoma (cHL) following front-line treatment failure is second line therapy (SLT) aimed to achieve complete response (CR), followed by consolidation with high dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). No one standard SLT exists and options include regimens containing platinum, gemcitabine, and more recently brentuximab vedotin (BV). Complete response rates associated with these regimens range from 50-70%. Due to the increasing use of BV in the front-line setting, development of SLT regimens that are both highly effective and BV-sparing are needed. Programmed death-1 (PD-1) inhibitors are highly active in RR cHL and have the potential to enhance the efficacy of standard chemotherapy. Here we report the results of our phase II study evaluating a novel anti-PD-1-based regimen, pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembrolizumab-GVD), as SLT for RR cHL. Methods: Transplant eligible patients (pts) with RR cHL following failure of 1-line of therapy were eligible. Treatment consisted of 2 to 4 cycles of pembrolizumab (200mg IV, day 1), gemcitabine (1000mg/m2 IV, days 1 and 8), vinorelbine (20mg/m2 IV, days 1 and 8) and liposomal doxorubicin (15mg/m2, days 1 and 8), given on 21-day cycles. Pts who achieved CR by PET (Deauville ≤3) after 2 or 4 cycles proceeded to HDT/AHCT. HDT/AHCT was carried out according to institutional standards and BV maintenance was allowed following HDT/AHCT. The primary endpoint was CR rate after 2 or 4 cycles of pembrolizumab-GVD. Enrollment occurred according to a Simon 2-stage design with sample size based upon a projected CR rate of 70%. In stage 1, 23 pts enrolled and 12 or more CRs were required to proceed to stage II;in stage II, an additional 16 pts enrolled. Out of a total of 39 pts, 24 CRs were required to declare this regimen promising. Results: Among 39 patients enrolled, 37 are evaluable for toxicity (2 pts have not yet started treatment) and 34 are evaluable for response (4 pts too early, 1 pt found to have composite lymphoma after enrollment). Of 37 treated pts, median age is 36 (range 21-71), 43% are male, 23 (62%) had advanced stage disease, and 15 (41%) had primary refractory disease. With regard to RR cHL risk factors (B-symptoms, extranodal disease, and relapse/refractory disease within 1 year of initial treatment), 4(11%) had no risk factors (RFs), 21 (57%) had 1 RF, 9 (24%) had 2 RFs, and 3 (8%) had all 3 RFs. Treatment was well tolerated with most adverse events being grade 1 or 2 (see figure 1). Grade 3 AEs included rash (n=1), elevated AST/ALT (n=3), oral mucositis (n=2), and neutropenia (n=3). Figure 2 shows the outcome for all 37 treated pts. Among 34 evaluable pts, 31 (91%) achieved CR after 2 cycles and 3 achieved partial response. An additional 1 pt achieved CR after 4 cycles of pembrolizumab-GVD, therefore in total, 32 of 34 (94%) achieved CR following pembrolizumab-GVD. 4 pts with CR after 2 cycles received an additional 2 cycles of pembrolizumab-GVD in order to delay HDT/AHCT during the height of the COVID-19 pandemic (n=3) or due to refusing HDT/ASCT (n=1). To date, 32 have undergone HDT/AHCT following 2 (n=27) or 4 (n=5) cycles of treatment. 1 pt is awaiting HDT/AHCT;1 pt refused HDT/ASCT and received pembrolizumab maintenance instead. 2 pts received involved site radiation therapy to initial area of relapsed disease prior to planned HDT/AHCT and 10 pts received post-HDT/ASCT maintenance with BV. Median follow-up post-HDT/AHCT is 9 mos (range 0.03-20.9 mos) and all pts remain in remission to date. Conclusion: Second-line therapy with pembrolizumab-GVD is a highly effective and well-tolerated regimen that can efficiently bridge pts with RR cHL to HDT/AHCT. Updated results including all 39 enrolled pts will be presented at the meeting. Given the high CR rate observed with pembrolizumab-GVD, an expansion cohort evaluating 8 cycles of pembrolizumab maintenance (instead of HDT/AHCT) for patients who achieve CR af er 4 cycles of pembrolizumab-GVD is planned. [Formula presented] Disclosures: Moskowitz: Merck: Consultancy;Incyte: Research Funding;Miragen Therapeutics: Consultancy;Seattle Genetics: Consultancy;Imbrium Therapeutics, L.P.: Consultancy;Merck: Research Funding;Seattle Genetics: Research Funding;Bristol-Myers Squibb: Research Funding. Shah: Amgen Inc.: Research Funding;Janssen: Research Funding. Kumar: AbbVie: Research Funding;Celgene: Honoraria, Other: Honoraria for Advisory Board;Seattle Genetics: Research Funding;Astra Zeneca: Honoraria, Other: Honoraria for Advisory Board;Celgene: Research Funding;Kite Pharmaceuticals: Honoraria, Other: Honoraria for Advisory Board;Adaptive Biotechnologies,: Research Funding;Pharmacyclics: Research Funding. Lahoud: MorphoSys: Other: Advisory Board. Batlevi: Life Sci, GLG, Juno/Celgene, Seattle Genetics, Kite: Consultancy;Janssen, Novartis, Epizyme, Xynomics, Bayer, Autolus, Roche/Genentech: Research Funding. Hamlin: J&J Pharmaceuticals: Research Funding;Portola: Research Funding;Incyte: Research Funding;Portola Pharmaceutics: Consultancy;Juno Therapeutics: Consultancy;Karyopharm: Consultancy;Celgene: Consultancy;Molecular Templates: Research Funding. Straus: Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees;Imedex, Inc.: Speakers Bureau;Targeted Oncology: Consultancy, Speakers Bureau;NY Lymphoma Rounds: Consultancy;Takeda Pharmaceuticals: Research Funding, Speakers Bureau;OncLive: Speakers Bureau;Elsevier: Membership on an entity's Board of Directors or advisory committees, Other: CME writer;ASH: Other: Conference in December 2019 on HL to other physicians during ASH;Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Horwitz: ASTEX: Consultancy;Verastem: Consultancy, Research Funding;Myeloid Therapeutics: Consultancy;Miragen: Consultancy;Kura Oncology: Consultancy;Janssen: Consultancy;GlaxoSmithKline: Consultancy;Daiichi Sankyo: Research Funding;C4 Therapeutics: Consultancy;Affirmed: Consultancy;Vividion Therapeutics: Consultancy;Beigene: Consultancy;Portola: Consultancy, Research Funding;Mundipharma: Consultancy;Innate Pharma: Consultancy;Corvus: Consultancy;Trillium: Consultancy, Research Funding;Seattle Genetics: Consultancy, Research Funding;Millenium/Takeda: Consultancy, Research Funding;Kyowa Hakka Kirin: Consultancy, Research Funding;Infinity/Verastem: Research Funding;Forty Seven: Consultancy, Research Funding;Celgene: Consultancy, Research Funding;Aileron: Consultancy, Research Funding;ADCT Therapeutics: Consultancy, Research Funding. Falchi: Genmab: Research Funding;Roche: Research Funding. Joffe: Epizyme: Membership on an entity's Board of Directors or advisory committees;AstraZeneca: Membership on an entity's Board of Directors or advisory committees. Noy: Pharmacyclics: Research Funding;Pharmacyclics: Consultancy;Janssen: Consultancy;Rafael Pharma: Research Funding;NIH: Research Funding;Morphosys: Consultancy;Medscape: Consultancy;Targeted Oncology: Consultancy. Matasar: Teva: Consultancy;Genentech, Inc.: Consultancy, Honoraria, Research Funding;Merck: Consultancy;Bayer: Consultancy, Honoraria, Research Funding;Juno Therapeutics: Consultancy;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding;GlaxoSmithKline: Honoraria, Research Funding;IGM Biosciences: Research Funding;Janssen: Honoraria, Research Funding;Pharmacyclics: Honoraria, Research Funding;Immunovaccine Technologies: Honoraria, Research Funding;Rocket Medical: Consultancy, Research Funding;Takeda: Consultancy, Honoraria;Daiichi Sankyo: Consultancy;Seattle Genetics: Consultancy, Honoraria, Research Funding. Vardhana: Other: Other: SAV has received honoraria from Agios Pharmaceuticals and Rheos Pharmaceuticals, is an advisor for Immunai and has consulted for ADC Therapeutics. von Keudell: Genentech: Research Funding;Bayer: Research Funding;Pharmacyclics: Research Funding. Zelenetz: Novartis: Consultancy;Janssen: Consultancy;Celge e: Consultancy;Amgen: Consultancy;Adaptive Biotechnology: Consultancy;BeiGene: Membership on an entity's Board of Directors or advisory committees;Roche: Research Funding;Gilead: Research Funding;Genentech/Roche: Consultancy;Gilead: Consultancy;Sandoz: Research Funding;Celgene: Research Funding;MEI Pharma: Research Funding;MorphoSys: Research Funding. OffLabel Disclosure: Pembrolizumab as second-line therapy for Hodgkin lymphoma
ABSTRACT
INTRODUCTION: Nodal PTCL with T-follicular helper phenotype (PTCL-TFH), which includes angioimmunoblastic T-cell lymphoma (AITL), is characterized by recurrent mutations affecting epigenetic regulators such as TET2, DNMT3A, IDH2 and RHOA. The association of aberrant DNA methylation with lymphomagenesis provides rationale for clinical application of hypomethylating agents. Azacitidine, an epigenetic modifier which inhibits DNA methyltransferase, has shown clinical activity as a single agent and in combination in R/R PTCL. We report the findings of the first study of oral azacitidine (CC-486) plus CHOP as initial treatment for PTCL (ClinicalTrials.gov - NCT03542266). METHODS: This phase 2 study prioritized enrollment of PTCL-TFH. Subjects received CHOP on day 1 of each cycle for 6 cycles. Priming with oral azacitidine (CC-486) at 300 mg daily was administered for 7 days prior to cycle 1 of CHOP, and for 14 days before CHOP cycles 2-6. Supportive care included mandatory G-CSF. The primary endpoint is CR per 2014 IWG criteria. Secondary endpoints include ORR, safety and survival. Correlative biomarker studies are planned to assess genomic mutations by next-generation-sequencing (NGS), in addition to methylation and transcription profiles. Using a Simon two-stage design comparing an CR of ≥60% with treatment to an unacceptable CR of ≤35% (alpha=10%, power=80%), 9 or more CR out of 17 enrolled patients were required to declare the treatment worthy of further study. RESULTS: From 6/2018 to 3/2020, 21 subjects with previously untreated PTCL were enrolled at 4 centers, and the study met its accrual. At study entry, 17 patients (81%) had PTCL-TFH (16 AITL and 1 TFH), 3 with PTCL-NOS, 1 with ATLL, including 5 (24%) with CD30+ disease. The median age was 66 years (range 22-77), and the M:F ratio was 1.6:1. Nineteen (90%) had stage III/IV disease, 10 (48%) had elevated LDH, 7 (33%) had bone marrow involvement, and 9 (43%) had IPI 3-5. Treatment was generally well tolerated with expected side effects. Grade 3-4 hematologic toxicities included neutropenia (71.4%), thrombocytopenia (9.5%) and anemia (14.3%), with febrile neutropenia uncommon (14.3%). Grade 3-4 non-hematologic toxicities included fatigue (14.3%), hyponatremia (14.3%), diarrhea (4.8%), vomiting (4.8%), rash (4.8%), and elevated ALT (4.8%). One incidence each of influenza A, COVID-19 pneumonia, C.diff and strongyloides hyperinfection were observed and treated. There was no study treatment-related mortality to date. As of July 2020 at a median follow-up of 7 months (range 4-25 months), one subject withdrew consent after cycle 1 (patient preference), and 20 subjects had at least one response assessment, including 15 completed treatment, 2 progressed during treatment, and 3 nearing completion of therapy. At interim assessment after cycle 3 (n=20), the ORR was 85% with CR at 55% (90%CI of 34.7%-74.1%). To date, the preliminary end-of-treatment (EOT, n=17) CR was 76.5% (90%CI of 53.9%-91.5%) for all evaluable patients and was 86.7% for 15 PTCL-TFH, exceeding primary endpoint threshold. CR did not correlate with CD30 expression. The estimated 1-yr PFS for all patients was 56.8% (95%CI of 26.3%-87.3%), with 1-yrs PFS for PTCL-TFH at 61.1% (95%CI of 29.5%-92.7%), and the estimated 1-yr OS for all patients was 74.4% (95%CI of 48.8%-100.0%), with 1-yr OS for PTCL-TFH at 88.9% (95%CI of 68.4%-100.0%). Mutational status by NGS was determined in 15 patients to date. The frequencies of the TET2, RHOA, DNMT3A, and IDH2 mutations were 73%, 40%, 13% and 13%, respectively. TET2 mutations were significantly associated with CR (p=0.014), favorable PFS (p-0.012) and OS (p=0.042). In contrast, DNMT3A mutations were associated with adverse OS (p=0.028). CONCLUSIONS: This study provides the first demonstration that addition of hypomethylating agent oral azacitidine (CC486) to CHOP as initial therapy is feasible, safe, and induces high CR rate in PTCL-TFH subtype, with expected side effects. Although preliminary, the EOT CR to date exceeds the threshold of meeting study primary endpoint. Final efficacy data as well as response according to subtype and mutational profiling will be updated at ASH. This active combination will be further evaluated in the upcoming ALLIANCE/Intergroup randomized study A051902, comparing oral azacitidine-CHO(E)P with duvelisib-CHO(E)P against CHO(E)P in CD30 negative PTCL. [Formula presented] Disclosures: Ruan: Seattle Genetics: Research Funding;AstraZeneca: Consultancy, Research Funding;Celgene: Consultancy, Research Funding;Juno: Consultancy;BMS: Consultancy, Research Funding;Pharmacyclics: Research Funding;Kite Pharma: Consultancy. Moskowitz: Seattle Genetics: Research Funding;Incyte: Research Funding;Merck: Consultancy;Seattle Genetics: Consultancy;Bristol-Myers Squibb: Research Funding;Merck: Research Funding;Imbrium Therapeutics, L.P.: Consultancy;Miragen Therapeutics: Consultancy. Mehta-Shah: Bristol Myers-Squibb: Research Funding;Genetech: Research Funding;Innate Pharmaceuticals: Research Funding;Kyowa Kirin: Consultancy;Verastem: Research Funding;Karyopharm Therapeutics: Consultancy;Celgene: Research Funding;C4 Therapeutics: Consultancy. Sokol: EUSA Pharma: Consultancy, Honoraria, Speakers Bureau;Kymera Therapeutics: Membership on an entity's Board of Directors or advisory committees;Kyowa/Kirin Inc.: Membership on an entity's Board of Directors or advisory committees. Horwitz: Portola: Consultancy, Research Funding;Aileron: Consultancy, Research Funding;Celgene: Consultancy, Research Funding;Beigene: Consultancy;Daiichi Sankyo: Research Funding;C4 Therapeutics: Consultancy;ADCT Therapeutics: Consultancy, Research Funding;Millenium/Takeda: Consultancy, Research Funding;Innate Pharma: Consultancy;Corvus: Consultancy;Trillium: Consultancy, Research Funding;Kyowa Hakka Kirin: Consultancy, Research Funding;GlaxoSmithKline: Consultancy;Mundipharma: Consultancy;Infinity/Verastem: Research Funding;Forty Seven: Consultancy, Research Funding;Seattle Genetics: Consultancy, Research Funding;Miragen: Consultancy;Myeloid Therapeutics: Consultancy;Verastem: Consultancy, Research Funding;Vividion Therapeutics: Consultancy;Affirmed: Consultancy;ASTEX: Consultancy;Janssen: Consultancy;Kura Oncology: Consultancy. Rutherford: LAM Therapeutics: Research Funding;Juno: Consultancy;AstraZeneca: Consultancy;Seattle Genetics: Consultancy;Genentech/Roche: Research Funding;Regeneron: Research Funding;Celgene: Consultancy;Heron: Consultancy;Karyopharm: Consultancy, Research Funding;Dova: Consultancy;Kite: Consultancy. Coleman: Novartis Pharmaceuticals: Research Funding;Innocare: Research Funding;Merck Sharp & Dohme Corp.: Research Funding;BeiGene: Research Funding;Acerta: Research Funding;Ipsen Group: Research Funding;BMS (Celgene Corporation): Research Funding;AstraZeneca Pharmaceuticals, LP: Research Funding;Karyopharma Therapeutics, Inc.: Research Funding;ARCUS Biosciences: Research Funding;AstraZeneca Pharmaceuticals, LP (Acerta Pharma BV Trials): Research Funding;Incyte Corporation: Research Funding;Eli Lilly and Company: Research Funding;EMD Serono Research and Development Institute Inc.: Research Funding;Genetech (F. Hoffman-LaRoche Ltd): Research Funding;Hutchinson MediPharma, LTD: Research Funding;Klus Pharma, Inc.: Research Funding;MeiPharma, Inc.: Research Funding;Seattle Genetics: Research Funding;Boston BIoMedical, Inc.: Research Funding. Melnick: Jubilant: Consultancy;Epizyme: Consultancy;Constellation: Consultancy;Janssen: Research Funding;Daiichi Sankyo: Research Funding. Cerchietti: BMS: Research Funding. Leonard: ADC Therapeutics: Consultancy;MEI Pharma: Consultancy;Bayer: Consultancy;Gilead/Kite: Consultancy;Karyopharm: Consultancy;GenMab: Consultancy;Regeneron: Consultancy;Sutro: Consultancy;AstraZeneca: Consultancy;Roche/Genentech: Consultancy;BMS/Celgene: Consultancy;Epizyme: Consultancy;Miltenyi: Consultancy. Martin: Regeneron: Consultancy;I-MAB: Consultancy;Sandoz: Consultancy;Janssen: Consultancy;Karyopharm: Consultancy, Research Funding;Teneobio: Consultancy;Bayer: Consultan y;Beigene: Consultancy;Cellectar: Consultancy;Incyte: Consultancy;Kite: Consultancy;Morphosys: Consultancy;Celgene: Consultancy. OffLabel Disclosure: Oral azacitidine (CC-486) as hypomethylating agent for the treatment of peripheral T-cell lymphoma