The use of myeloablative preparative therapy and allogeneic stem cell transplantation (alloSCT) as salvage therapy for adult patients with relapsed hematologic malignancy after autologous stem cell transplantation (autoSCT) is generally unsuccessful due to very high treatment-related mortality rates. We evaluated the outcome of HLA-matched related donor alloSCT following nonmyeloablative preparative therapy in 13 patients (median age, 38 years) with relapsed hematologic malignancies (Hodgkin's disease, n = 4; Hodgkin's disease and advanced myelodysplastic syndrome, n = 1; non-Hodgkin's lymphoma, n = 6; multiple myeloma, n = 2) after initial autoSCT. Median time from autoSCT to alloSCT was 12 months (range, 3-24 months); 6 patients had chemotherapy-refractory disease following autoSCT, 6 were in untreated relapse, and 1 had a partial response from salvage chemotherapy. Preparative therapy consisted of cyclophosphamide, 150-200 mg/kg; peritransplantation anti-thymocyte globulin; thymic irradiation (in patients who had not received previous mediastinal irradiation); and a very short course of cyclosporine as GVHD prophylaxis. All patients achieved initial mixed chimerism as defined by greater than 1% donor peripheral white blood cells. Seven patients, who had no evidence of GVHD, received prophylactic DLI beginning 5 to 6 weeks after transplantation for conversion of mixed chimerism to full donor hematopoiesis and to optimize a graft-versus-tumor effect. Six patients showed conversion to full donor chimerism and 1 lost the graft. Grade II or greater acute GVHD occurred in 9 patients. Seven patients achieved a complete response; 6 had no response. The median survival time of the 13 patients is currently 10 months (range, 3-39 months), with an overall survival probability at 2 years of 45% (95% confidence interval [CI], 19%-73%) and a disease-free survival probability at 2 years of 37.5% (95% CI, 12%-65%). Thus, this novel nonmyeloablative alloSCT strategy followed by prophylactic DLI was well tolerated and can result in durable disease-free survival among patients with advanced hematologic malignancies after a failed autoSCT. Further follow-up and evaluation of additional patients are required to conclusively establish the role of this strategy in the treatment of hematologic malignancies after an autologous transplantation.

versus-host disease (GVHD) is one of most common complications following allogeneic hematopoietic cell transplantation (HCT) and the most significant contributor to morbidity and nonrelapse mortality. The physical burdens and psychosocial difficulties of these patients have not been described systematically. An exploration into the rates and correlates of mood and quality of life (QOL) in patients with chronic GVHD is necessary to develop a clinically relevant, evidence-based intervention to promote well-being. From July 2015 to July 2017, adult allogeneic HCT survivors with established moderate to severe chronic GVHD (N = 52) enrolled in a prospective, longitudinal study at a tertiary academic center. We examined the rates and correlates of depression and anxiety symptoms (Hospital Anxiety and Depression Scale) and explored whether constructs including coping strategies (Coping Inventory for Stressful Situations), symptom burden (Lee Symptom Assessment Scale), physical functioning (Human Activity Profile), and perceived social support (Medical Outcomes Study Social Support Survey) predicted QOL trajectory over time (Functional Assessment of Cancer TherapyÀBone Marrow Transplant) at the baseline, 3-month, and 6-month follow-up. Analyses adjusted for age, sex, chronic GVHD severity, and time since chronic GVHD diagnosis. At the baseline, 3-month, and 6-month follow-up, 32.7%, 31.1%, and 37.8% of patients reported clinically significant depression symptoms, and 30.8%, 20.0%, and 36.4% reported clinically elevated anxiety symptoms, respectively. Adjusting for covariates, greater use of negative emotion-oriented coping (b = 0.20, P = .002), less use of task-oriented coping (b = À0.10, P = .021), worse physical functioning (b = À0.07, P = .004), and higher symptom burden (b = 0.07, P = .002) were independently associated with depression symptoms at baseline. Greater use of negative emotion-oriented coping (b = 0.28, P < .001) and worse physical functioning (b = À0.05, P = .034) were independently associated with anxiety at baseline. Patients who used more negative emotion-oriented coping (b = À0.58, P = .035), had less task-oriented (b = 0.40, P = .028) and social diversion-oriented coping (b = 0.35, P = .039), and had higher symptom burden (b = À0.30, P = .001), worse physical functioning (b = 0.32, P < .001), and lower perceived social support (b = 6.47, P = .003) at baseline reported poorer QOL over time. The unmet physical and psychosocial needs of patients with chronic GVHD are substantial and warrant investigation into evidence-based interventions that may improve QOL and mood by targeting modifiable psychosocial constructs identified in this study.

A multimodal intervention to address sexual dysfunction integrated within the transplant clinic is feasible with encouraging preliminary efficacy for improving sexual function, QOL, and mood in HCT survivors. Cancer 2018;124:2438-46. © 2018 American Cancer Society.

Characterization of molecular alterations in acute myeloid leukemia (AML) has led to development of targeted therapies, including FLT3 and IDH1/2 inhibitors. Maintenance therapy following hematopoietic cell transplantation (HCT) has shown substantial promise. Enasidenib (ENA), a selective IDH2 inhibitor, was associated with impressive rates of response in relapsed/refractory (R/R) AML and is now FDA-approved for this indication. We sought to assess the tolerability and define the maximum tolerated dose (MTD) of ENA as maintenance following HCT for IDH2-mutated myeloid malignancy. HCT-eligible patients (pts) ≥ 18 years with AML in remission, or myelodysplastic syndrome (MDS) with &lt;5% marrow blasts, were enrolled. There were no restrictions on conditioning or donor type. A 2-step registration process was utilized; 1 before HCT and 1 before ENA initiation. Before HCT, pts were required to have normal organ and recovered marrow function (neutrophils &gt; 1000/µL and platelets &gt; 50000/µL). Those with prior HCT, active disease, QTc ≥450ms, and active infections were excluded. ENA was initiated between day 30 and 90 after HCT, at which time the following were required: chimerism ≥70% of donor origin among blood/marrow cells, no acute graft versus host disease (aGVHD) requiring ≥0.5mg/kg/day prednisone or equivalent, and no relapse. ENA was taken orally (po) daily (qd) in 28-day cycles. The period for dose-limiting toxicity (DLT) evaluation was the first cycle, escalation to successive levels was guided by DLT incidence, and 2 levels (50mg,100mg) were studied. Following establishment of MTD or recommended phase 2 dose (RP2D), 10 pts would be enrolled in an expansion cohort. Pts were monitored for relapse and toxicity and continued until disease progression, intolerable toxicity, or receipt of 12 cycles. Nineteen pts have been registered prior to HCT at 3 sites, Massachusetts General Hospital, Dana Farber Cancer Institute, and Johns Hopkins Hospital. Three pts could not initiate ENA following HCT; 2 due to logistic challenges of the COVID pandemic and 1 due to relapse. The remaining 16 pts initiated ENA treatment. The median age was 61 years (range 31-76); 12 (75%) were male, and 13 (81%) were Caucasian. Fourteen (88%) had AML, of which 6 were AML with MDS related changes and 2 had antecedent myeloproliferative neoplasm. Two pts (13%) had MDS. Among these 16 pts, 9 (56%) had IDH2 R140, and 5 (25%) had IDH2 R172 mutations. IDH2 subtype data was unavailable for 2 pts. Of 15 pts with available data from time of diagnosis, 11 (73%) had intermediate-risk and 4 (27%) had adverse-risk cytogenetics. Among these 15 pts, common concurrent mutations were DNMT3A (47%), SRSF2 (33%), and RUNX1 (33%). Eleven AML pts (85%) received intensive versus non-intensive therapies (15%) prior to HCT, and among all pts, 7 (44%) had received ENA prior to HCT. HCT data was available for all 16 pts; 4 pts (25%) received myeloablative, and 12 (75%) received reduced-intensity conditioning. Nine pts (56%) had a matched unrelated, 6 (38%) had haploidentical, and 1 (6%) had a matched related donor HCT. Three pts were enrolled at the 50mg dose level, 6 pts at 100mg, and after no DLTs were detected, the remaining were enrolled in an expansion cohort at 100mg qd. Median follow-up (F/U) for surviving patients is currently 11.7 months (range 1.5-18.9). 2 pts (13%) have relapsed during F/U, at 96 and 364 days post HCT. Additional ≥grade (G) 3 toxicities detected during treatment, possibly or probably related to ENA, included neutropenia, anemia, and bilirubinemia. Six pts (38%) required dose interruptions lasting a median 19 days (range 7-25), 4 required a dose reduction to 50mg, and 1 stopped treatment due to G3 bilirubinemia. In total, 3 pts (18%) discontinued study treatment, 1 for aforementioned G3 bilirubinemia, 1 to pursue a GVHD trial, and 1 for relapse. Six pts have completed the 12-month f/u without relapse, and 7 remain on study. 15 of 16 pts remain alive. Thus far, 3 pts have experienced ≥ G2 aGVHD, and 4 had moderate chronic GVHD. Serial measurement of 2HG is being conducted on samples, and these will be reported. Enasidenib is well-tolerated as post-HCT maintenance therapy for myeloid malignancy at the RP2D of 100mg qd. No DLTs have been detected, and a low rate of post-HCT relapse has been identified to date, although longer f/u is needed. Larger, randomized studies of ENA in the post-SCT setting would determine the true efficacy of this agent as maintenance therapy. Disclosures Fathi: Blueprint: Consultancy; Jazz: Consultancy; Amgen: Consultancy; Newlink Genetics: Consultancy; Pfizer: Consultancy; Abbvie: Consultancy; Seattle Genetics: Consultancy, Research Funding; Agios: Consultancy, Research Funding; PTC Therapeutics: Consultancy; Takeda: Consultancy, Research Funding; Boston Biomedical: Consultancy; Amphivena: Consultancy; BMS/Celgene: Consultancy, Research Funding; Kite: Consultancy; Trovagene: Consultancy; Forty Seven: Consultancy; Novartis: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Trillium: Consultancy; Kura Oncology: Consultancy. Soiffer:Gilead: Consultancy; Novartis: Consultancy; Juno: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; VOR Biopharma: Consultancy; alexion: Consultancy; Rheos Therapeutics: Consultancy; Cugene: Consultancy; Precision Bioscience: Consultancy; Be the Match/ National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Kiadis: Membership on an entity's Board of Directors or advisory committees; Mana Therapeutics: Consultancy. Levis:Menarini: Honoraria; Amgen: Honoraria; FujiFilm: Honoraria, Research Funding; Astellas: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria. Mims:Novartis: Speakers Bureau; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Abbvie: Membership on an entity's Board of Directors or advisory committees. Devine:Magenta Therapeutics: Consultancy. Defilipp:Incyte: Research Funding; Regimmune: Research Funding; Syndax Pharmaceuticals: Consultancy. Spitzer:Jazz Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees. Frigault:Celgene: Consultancy; Arcellx: Consultancy; Novartis: Consultancy, Research Funding; Gilead/Kite: Consultancy, Research Funding. Amrein:Amgen: Research Funding; AstraZeneca: Consultancy, Research Funding; Takeda: Research Funding. Hobbs:Incyte: Research Funding; Merck: Research Funding; Bayer: Research Funding; Constellation: Honoraria, Research Funding; Jazz: Honoraria; Celgene/BMS: Honoraria; Novartis: Honoraria. Brunner:Janssen: Research Funding; Acceleron Pharma Inc.: Consultancy; GSK: Research Funding; Xcenda: Consultancy; Takeda: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Jazz Pharma: Consultancy; Forty Seven, Inc: Consultancy; Celgene/BMS: Consultancy, Research Funding; Biogen: Consultancy; Astra Zeneca: Research Funding. Narayan:Genentech: Other: Prior Spouse employment within 24 months and prior spouse equity divested within past 24 months; Takeda: Other: Prior Spouse employment within 24 months; Sanofi-Genzyme: Other: Current Spouse employment . Chen:AbbVie: Other: Data and Safety Monitoring Board Member; Incyte Corporation: Consultancy; Takeda: Consultancy; Actinium: Other: Data and Safety Monitoring Board Member; Equillium: Other: Data and Safety Monitoring Board Member; Magenta: Consultancy; Kiadis: Consultancy. OffLabel Disclosure: Enasidenib as post-transplant maintenance therapy