ALBERT

Description: Abstract 4144 Background The treatment of elderly patients with AML remains controversial due to the inferiority of outcomes associated with standard intensive induction regimens. Hypomethylating agents have been shown to improve quality of life and survival in patients with myelodysplastic syndromes and have activity in AML. We report our experience with decitabine in elderly patients with previously untreated or refractory AML. Patients and methods We conducted a retrospective analysis of 30 patients (11 males and 19 females) with AML who were ineligible for intensive induction chemotherapy and received decitabine (20 mg/m2 for 5 days every 28 days). Median age at diagnosis was 67 years (range 40 to 91 years), 28/30 (93.3%) patients were 60 years of age or older. Twelve (40%) patients had cytogenetic abnormalities (7 – unfavorable). ECOG performance status was 0-1 for 26 patients, 2 for 3 patients and 3 for 1 patient. Seven (23.3%) patients had secondary AML and 23 (76.7%) patients had de novo AML, of which 10 demonstrated evidence of multilineage dysplasia on bone marrow biopsy. Eleven (36.7%) patients progressed after prior therapy which included intensive induction therapy in 10 patients (followed by stem cell therapy in 4 patients) and tipifarnib in 1 patient. Nineteen (63.3%) patients received decitabine as first-line therapy. Clearance of blasts from the peripheral blood was monitored and used as an indicator of improved relapse-free survival in AML. Overall survival was defined as the time from the day 1 of decitabine treatment to death. Results Patients received a median of 5 cycles of decitabine. Seven patients (23.3%) received ≥10 cycles. All patients received decitabine in the outpatient setting. No hospitalizations were required to administer treatment. Peripheral blood blast clearance was documented in 23 (76.7%) patients including 7 patients who achieved a CR/CRi, and 2 PR. The median time to response was 2 months with median duration of 3 months. Seven patients (23.3%) did not respond to treatment. To date, 19 (63.3%) patients have died after 5-24 months of therapy and 11 (36.7%) remain alive. The median survival was 12 months in all patients (range 4 to 24 months) and 14 months in the 17 patients who received more than 4 cycles of therapy. Overall survival was 82.4% at 6 months and 47.9% at 12 months. Eleven (36.7%) patients survived for 〉1 year. Seven patients underwent allogeneic stem cell therapy after achieving CR/CRi on decitabine. Three patients received stem cells from siblings or offspring; 3 patients had a matched unrelated donor and 1 patient received umbilical cord stem cells. Three patients are alive after a median follow-up of 12 months. Three patients died of relapsed AML and 1 patient died of infectious complications of transplant. Decitabine was well tolerated. Ten patients experienced minimal nausea amenable to ondansetron with no documented episodes of vomiting. Seventeen patients developed grade 4 neutropenia and 3 patients grade 4 thrombocytopenia during the course of treatment. Fourteen (46.7%) patients underwent a total of 37 hospitalizations. Common reasons for hospitalizations were: febrile neutropenia (19), pneumonia (6) and thrombocytopenia (3). Sixteen (53.3%) patients never required hospitalization while undergoing treatment. No deaths were attributed to complications related to therapy. Decitabine administered as an outpatient is an effective treatment option for elderly and high risk patients with AML. It has a favorable chemotherapy-related toxicity profile and is associated with a decreased frequency of hospitalizations. Decitabine may facilitate a subsequent allogeneic transplant in eligible patients and should be considered a treatment option for high risk patients with AML. Disclosures: Off Label Use: decitabine in AML.

Description: Autologous stem cell transplantation (SCT), a standard therapy for patients with multiple myeloma (MM), has been offered continuously for over 25 years at our center. During this time, there have been significant advances in therapy and marked improvements in survival. We performed a single-center retrospective study comparing patients transplanted from 1988-2000 (cohort A) and 2001-2012 (cohort B). We evaluated differences at, toxicities of, and outcomes with and after SCT. This comparison highlights the contributions of advances in SCT-related conditioning regimens, supportive care and the impact of new therapeutic agents on patient outcomes. Data were extracted from two internal clinical and stem cell databases and from medical chart reviews of all patients undergoing SCT for MM from 1988-2012. Disease responses were assessed with IMWG response criteria. The National Death Index was queried for patients lost to follow-up, without date of death, or without cause of death. Progression-free (PFS) and overall survival (OS) were defined as time from SCT to progression and/or death and estimated by Kaplan-Meier (two-sided log rank test). Patients with a second SCT or allogeneic SCT were censored at the date of second SCT. Multivariate analysis was performed using Cox's Proportional Hazard Regression models. We calculated adjusted survival probabilities by employing a stepwise model selection to identify significant covariates. Factors that were significant at 0.15 level were kept in the final model. Patient characteristics of the cohorts (A=63, B=116) including gender, lab values at diagnosis, renal and skeletal involvement, M-protein isotypes, staging, pre-SCT screening and infectious disease testing, were no different. Cohort A was younger at SCT (54 vs 57 years) and transplanted later post-diagnosis. More in cohort A had been treated with melphalan (MEL) (48% vs 4%) and palliative radiation (XRT) to bone lesions (54% vs 26%) pre-SCT. MM disease status was significantly different at SCT for A and B (Table 1). Three quarters of patients in cohort A were mobilized with cyclophosphamide and G-CSF (Cy-G) but 23% were collected in steady-state or after GM-CSF, while 99% in cohort B were mobilized with Cy-G or G alone. Notable aspects of conditioning regimens and peri-transplant complications are shown in Table 1. Exposure to prior XRT in cohort A correlated with development of secondary MDS/AML. OS post-SCT differed between the two cohorts (2.8 vs 7.9 years, P 〈 0.01) (Figure 1). No patients in cohort A received a novel agent pre-SCT compared to 68% in cohort B including 〉30% of cohort B receiving pre-SCT bortezomib. CR/VGPR status at SCT predicted improved OS (P = 0.04) while pre-SCT exposure to oral MEL predicted worse OS (HR 1.97, P = 0.02). Patients in cohort A died shortly after post-SCT relapse, whereas those in cohort B lived longer after relapse (1.0 vs 2.7 years, P 〈 0.01). Median OS of patients who received a novel agent at any time was not reached compared to 3.4 years for others. Cause of death differed between the two cohorts. More patients died of MM progression in cohort B (80% vs 58%), while more patients died of transplant related causes or secondary MDS in cohort A (19% vs 2%). In sum, we demonstrate a clear improvement in outcomes of MM patients selected to undergo first SCT over the past 25 years. OS has improved alongside reductions in TRM. Novel agents have contributed to these improvements although advances in SCT and supportive care are also important contributors. Further research into more efficacious treatments, such as monoclonal antibody therapy, is required to continue the improvements in SCT for MM. Table 1. Variable Cohort A1988 - 2000(N = 63) (%) Cohort B2001 - 2012(N = 116) (%) P -value Months from diagnosis to SCT 12.7 (5.6-95.3) 8.9 (4.2-50.6) 〈 0.01 Patients 〉 64 years old 3 (5) 19 (16) 0.024 MM status at SCT CR 15 (24) 31 (27) 〈 0.01 VGPR 2 (3) 27 (23) PR 29 (48) 40 (34) SD 5 (8) 9 (8) Refractory 6 (10) 5 (4) Relapsed 5 (8) 4 (3) Conditioning regimen MEL 140 7 (11) 15 (13) 〈 0.01 MEL 200 2 (3) 99 (85) MEL 140/TBI 41 (65) 2 (2) MEL 140/TBI/Cy 12 (19) 0 (0.00) MEL 140/Cy 1 (2) 0 (0.00) Days in hospital for SCT 24 (13 - 64) 20 (11 - 36) 〈 0.01 Failure to engraft for platelets 9 (14) 1 (1) 〈 0.01 Treatment-related mortality (100d) 6 (10) 1 (1) 〈 0.01 MM response post-ASCT CR 26 (46) 59 (53) 〈 0.01 VGPR 6 (11) 31 (28) PR 21 (38) 18 (16) SD 2 (4) 4 (4) Relapsed 1 (2) 0 (0) Secondary MDS/AML 6 (10) 0 (0) 〈 0.01 Figure 1. Figure 1. Disclosures Relias: Genentech: Speakers Bureau. Miller:Biogen Idec: Consultancy; AbbVie: Speakers Bureau; Millennium: Speakers Bureau; Onynx: Speakers Bureau. Comenzo:Prothena: Research Funding; Karyopharm: Research Funding; Janssen: Research Funding; Takeda Millennium: Membership on an entity's Board of Directors or advisory committees; Takeda Millennium: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees.

Description: BACKGROUND: It is estimated that 〉1.4 million people in the US are living with chronic HBV, many of whom are unaware of their infection. Chronic infection is responsible for the majority of HBV-related morbidity and mortality ranging from hepatitis to fulminant hepatic failure. The monoclonal anti-CD20 antibody, rituximab, is used to treat a variety of malignant and non-malignant conditions. Its use is associated with reactivation of HBV (HBV-R), including in historically low risk populations (i.e., HBV core antibody (HBcAb) positivity) and HBV-R may occur 〉8-10 months after completion of therapy. Professional societies such as the CDC and Infectious Diseases Society of America (IDSA) recommend screening all persons receiving cytotoxic or immunosuppressive therapy for HBV infection, although not all guidelines surrounding this topic are consistent. The primary aim of this study was to determine the rate of rituximab-related HBV screening and HBV-R over a recent time period across multiple medical specialties and disease conditions. METHODS: We completed a single center, retrospective cohort study at an urban, academic medical center reviewing all patients (pts) ≥ 18 years of age who received rituximab 1/1/06 to 7/31/13 who had at least 12 months of follow-up following the final rituximab dose. Eligible pts were queried using an electronic pharmacy database and reviewed by 3 physicians. Detailed data included demographics, indication for rituximab, number of rituximab doses, HBV screening serology, vaccination status, and comorbidities and risk factors for HBV-R. RESULTS: We identified 407 pts; of these, 10 were excluded due inadequate follow-up, 7 for incomplete records, and 1 was due to age 24 months prior). Interestingly, the type of HBV screening tests varied widely with no consistent panel of serologies tested, although the majority of pts who had screening had testing for HBV surface antigen (90.7%). HBcAb was not checked as often (66%), which represents a subset of pts at risk for developing HBV-R. Of pts screened for HBcAb, 15/88 (17%) were found to be positive for HBV (n=14 HBcAb and n=1 pt was positive for HBV surface antigen). 8/15 pts had no known or obvious risk factors for HBV infection. Of the 14 pts testing positive for HBcAb prior to rituximab, only 1 pt received anti-HBV prophylactic therapy. 3 of 14 pts without HBV prophylaxis experienced HBV-R (all HBcAb+ lymphoma pts treated with rituximab/chemotherapy), one of who died due to multiorgan failure. CONCLUSION: At our academic center, we identified a relatively low rate of HBV screening amongst pts receiving rituximab irrespective of disease specialist or diagnostic condition. In addition, among pts who were screened, testing panels were inconsistent and a significant minority of pts did not have testing for HBcAb. Furthermore, we identified a relatively high rate of occult positivity for HBcAb including in a significant fraction of pts without known risk factors. It is advocated that a National unified guideline be instituted towards rituximab-related HBV screening and institutions implement and adhere to these guidelines. Likewise, a standardized panel of HBV serology is essential, both for initial testing and follow up. This is especially important given the increasing number of FDA approvals of other anti-CD20 and related monoclonal antibodies that carry similar risks of HBV-R. Disclosures Evens: Genentech: Honoraria, Speakers Bureau.

Description: Abstract 4153 The optimal preparative regimen for older patients undergoing hematopoietic stem cell transplantation (HSCT) is unclear. We routinely employ a reduced intensity conditioning regimen consisting of extracorporeal photopheresis (ECP) on days −6 and −5, Pentostatin 4 mg/m2/day by continuous infusion on days −4 and −3, and 600 cGy total body irradiation in 3 divided fractions on days −2 and −1 (“PPT regimen”) for patients greater than 60 years of age (Bone Marrow Transp 2004; 33:881). We now report outcomes of 38 consecutive patients ≥ 60 years old (median 62, range 60–70) (M 22, F 16) transplanted at our center between 1/1/00 and 4/1/11 for hematologic malignancies: AML (n=23), MDS (n=10), ALL (n=1), CLL (n=1), NHL (n=2) and MM (n=1). Twenty-six (68.4%) received matched related and 12 (31.6%) 6/6 matched unrelated donor (MUD) grafts. Twenty-five (65.8%) received marrow and 13 (34.2%) peripheral blood stem cell grafts. Median time to neutrophil engraftment was 16 days (3–25). Survival at day 100 was 84% (32/38), with a 13% TRM (5/38) and 3% (1/38) incidence of relapse-related death. Actuarial 1-year overall survival (OS) for all patients was 45% (95% CI 28 – 61%), and median OS in all patients was 10.6 months (95% CI 4.6 – 25.7 months). Estimated 1-year event-free survival, defined as freedom from relapse, progression, or death from any cause, was 44% (95% CI 27 – 59%). Median event-free survival for the entire cohort was 7 months (95% CI 3.6 – 25.6 months). Grade II and grades III/IV acute GvHD (aGvHD) occurred in 8 (21%) and 2 (5%) patients respectively within 1 to 8 weeks of HSCT (median 16 days). After day 100, 6 patients had died, 1 was missing data, and 23 (74% of remaining patients and 60% of the original cohort) had symptoms of GvHD. Fourteen met NIH consensus criteria for chronic GvHD (cGvHD) including 6 with severe classic or overlap cGvHD while 6 had recurrent, 2 persistent and 1 delayed aGvHD. Of those with aGvHD after day 100, 2 patients exhibited ≥ grade III disease. Median time to onset of cGvHD was 4.1 months (3.3 – 11.7). Among patients who received marrow as their stem cell source (n=25), incidence of grades II-IV aGvHD was 32% (24% grade II, 8% grade III/IV), and incidence of any GvHD from day 100 up to date of death or last follow-up was 68%. Among those who received blood stem cells (n=13) incidence of grades II-IV aGvHD was 15% (all grade II) and incidence of GvHD from day 100 until date of death or last follow-up was 83%. There was no statistically significant difference between those who received marrow versus blood stem cells with respect to incidence of either grade II-IV aGvHD or GvHD after day 100 (P =0.27 and 0.36). For those who received MUD transplants (n=12), incidence of grades II-IV aGvHD and of any post-day 100 GvHD were 42% (33% grade II, 8% grade IV) and 75% respectively, and in those who received related donor transplants (n=26) were 19% (15% grade II, 4% grade IV) and 74%, respectively. There was no statistically significant difference between MUD HSCT versus related donor HSCT patients with regard to grade II-IV aGvHD or GvHD after day 100 (P =0.14 and 0.94). In conclusion, our approach was well tolerated by HSCT patients 〉 60 years old, provided prompt myeloid recovery and had an acceptable incidence of post-day 100 severe chronic (19%) or 〉 grade II late acute GvHD (6%). Disclosures: Off Label Use: Pentostatin and Extracorporeal photopheresis are not FDA approved for conditioning prior to allogeneic transplant. Comenzo:Elan: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Neotope: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.