Abstract: Background: Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma (NHL). Although most patients with FL respond well to first-line therapy, they will inevitably relapse, and the subsequent course is often characterized by a pattern of recurrent relapses with progressively shorter intervals between treatment lines. Moreover, the use of multiple consecutive therapies often leads to refractory disease with severely limited treatment options, demonstrating the need for new therapies for this patient population. Currently approved phosphoinositide 3-kinase (PI3K) inhibitors are often poorly tolerated. Parsaclisib, a potent, highly-selective, next-generation PI3Kδ inhibitor, has shown promising activity in patients with previously treated B-cell malignancies. Here, we report preliminary results of CITADEL-203 (NCT03126019), a multicenter, open-label phase 2 study of parsaclisib in relapsed or refractory (R/R) FL. Methods: Key eligibility included, age ≥18 years, histologically confirmed R/R FL grade 1, 2, or 3a, ≥2 prior systemic therapies, Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, and ineligible for hematopoietic stem cell transplantation (HSCT). Patients were allocated to receive parsaclisib 20 mg once daily (QD) for 8 weeks followed by either 20 mg once weekly (weekly-dosing group [WG]) or 2.5 mg QD (daily-dosing group [DG] ). Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was required. Objective response rate (ORR) was the primary endpoint; complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety and tolerability were secondary endpoints. All radiology-based endpoints were based on independent review. Results: From March 2018 to 17January 2020 (data cut-off), 106 patients (WG, n = 22; DG, n = 84) were treated. Enrollment is ongoing (target: 120 patients). At cut-off, 39 (37%) patients had discontinued treatment, including 25 (24%) for disease progression. The median exposure (range) was 5.3 months (0.5-18.1). The median age was 67 years, and 54% of the patients were men. The median time since initial diagnosis was 6 years. At enrollment, most patients (92%) had an ECOG PS ≤1, and 43% had a Follicular Lymphoma International Prognostic Index score ≥3 (high risk). The median (range) number of prior systemic therapies was 2 (1−8); 20% of the patients had prior HSCT; 47% were refractory to and 41% had relapsed from their most recent therapy. At the data cut-off, 96 patients were evaluable for response, including 74 in DG (Table). The ORR and CRR were 69.8% (95% confidence interval [CI]: 59.6−78.7) and 13.5% respectively, in all evaluable patients, and 71.6% (95% CI: 59.9% - 81.5%) and 13.5%, respectively, in DG. The median time to response was 8 weeks. The median DOR (95% CI) was not reached among responders overall (9.2 months−not estimable) and those in DG (7.4 months−not estimable). The median PFS (95% CI) was 15.8 months (11.3−15.8) overall and 15.8 months (11.0−15.8) in DG. The median follow-up (range) for this population was 10.2 months (1.9−22.2) overall and 9.5 months (1.9−21.1) in DG. Among the 106 patients evaluable for safety, the most common treatment-emergent adverse events (TEAE) were diarrhea (27.4% of patients), nausea (22.6%), cough (18.9%), and fatigue (15.1%). The most common TEAEs grade ≥3 were diarrhea (9.4% of patients), neutropenia (6.6%), and colitis (3.8%). TEAEs leading to dose interruption or dose reduction occurred in 39.6% and 9.4% of patients, respectively. TEAEs leading to treatment discontinuation occurred in 16% of patients. Serious TEAEs observed in ≥2 patients included diarrhea (5.7% of patients), colitis (3.8%), and pleural effusion (1.9%). There were no fatal TEAEs. TEAEs of clinical interest included rash (12.3% of patients), exfoliative dermatitis (1.9%), pneumonia (0.9%), and PJP (0.9%). New or worsening grade ≥3 laboratory test values of clinical interest included increase in alanine/aspartate amino transferase (0.9%/0% of patients), and decrease in neutrophil count (8.5%), platelet count (0%), and hemoglobin (1.9%). Conclusion: Parsaclisib demonstrated a high rate of rapid and durable response, and had an acceptable safety profile and was generally well tolerated. These results demonstrate a favorable benefit-risk profile in R/R FL. Updated data will be presented. Disclosures Lynch: Morphosys: Consultancy; Takeda: Research Funding; Incyte: Research Funding; TG therapeutics: Research Funding; Rhizen: Research Funding; Bayer: Research Funding; Juno: Research Funding; Cyteir: Research Funding; Genentech: Research Funding. Paneesha:Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Janssen: Honoraria; AbbVie: Honoraria. Avigdor:Takeda, Gilead, Pfizer: Consultancy, Honoraria; Janssen, BMS: Research Funding. McKinney:Verastem: Consultancy; Pharmacyclics: Consultancy; Kite/Gilead: Honoraria, Speakers Bureau; Beigene: Research Funding; Celgene: Consultancy, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Molecular Templates: Consultancy, Research Funding; Nordic Nanovector: Research Funding; Novartis: Research Funding; BTG: Consultancy. Wahlin:Gilead Sciences: Research Funding; Roche: Consultancy, Research Funding. Belada:Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Celgene: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding. Canales:Celgene, Gilead, iQone, Janssen, Karyopharm, Novartis, F. Hoffmann-La Roche, Sandoz: Honoraria; Janssen, F. Hoffmann-La Roche, Sandoz, Takeda: Speakers Bureau. Cunningham:Bayer: Research Funding; OVIBIO: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Lilly: Research Funding; Janssen: Research Funding; Clovis Oncology: Research Funding; Celgene: Research Funding; MedImmune: Research Funding; Merck: Research Funding; Merrimack: Research Funding; Sanofi: Research Funding; AstraZeneca: Research Funding; 4SC: Research Funding. Morley:Kite: Honoraria; Janssen: Honoraria; Abbvie: Other: Conference Support; Takeda: Other: Conference Support; Roche: Other: Conference Support; Advisory board. Zheng:Incyte: Current Employment, Current equity holder in publicly-traded company. DeMarini:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Jiang:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Trněný:1st Faculty of Medicine, Charles University, General Hospital in Prague: Current Employment; Incyte: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company); MorphoSys: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Bristol Meyers Squibb: Consultancy, Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company); Celgene: Consultancy.

Abstract: Background: Follicular lymphoma (FL) is the second most common form of non-Hodgkin lymphoma (NHL) in Western countries, accounting for 20-30% of all NHLs (Hübel K. Hemasphere. 2020;4:e317). While most patients (pts) respond well to first-line therapy, they typically experience frequent relapses and progressively shorter duration of response with subsequent lines of therapy (Batlevi CL. Blood Cancer J. 2020;10:74; Rivas-Delgado A. Br J Haematol. 2019;184:753-9), and increasingly refractory disease with limited treatment options. Thus, there is an unmet need for effective treatment options for pts with relapsed or refractory (R/R) FL. Parsaclisib is a potent, highly selective, next-generation phosphatidylinositol 3-kinase (PI3K)δ inhibitor. Here we report results of the primary analysis of CITADEL-203 (NCT03126019, EudraCT 2017-001624-22), a phase 2, multicenter, open-label study of parsaclisib monotherapy in R/R FL. Methods: Eligible pts were ≥18 years of age, had histologically confirmed R/R FL (grade 1, 2, or 3a), had received ≥2 prior systemic therapies (not including PI3K inhibitors or Bruton's kinase inhibitors), had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, and were ineligible for hematopoietic stem cell therapy. Pts were allocated to receive 20 mg parsaclisib once daily (QD) for 8 weeks, followed by parsaclisib either 20 mg once weekly (weekly-dosing group [WG]) or 2.5 mg QD (daily-dosing group [DG] ). Prophylaxis for Pneumocystis jirovecii pneumonia was required. The primary endpoint was objective response rate (ORR) as determined by an independent review committee (IRC); secondary endpoints included complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety and tolerability. All radiology-based endpoints were confirmed by an IRC. Results: At data cutoff for the primary analysis (Jan 15, 2021), 126 pts (WG, n=23; DG, n=103) had been treated. The median (range) age was 67.5 (40-88) years, 55.6% of pts were male, and majority (93.7%) of pts had an ECOG PS ≤1. The median (range) time since initial diagnosis was 5.95 (0.2-32.2) years. 54.0% of pts had received 2 lines and 27.8% had received 3 lines of prior systemic therapy (median [range], 2 [1-8] ); 41.3% of pts had relapsed disease and 49.2% were refractory to their most recent prior therapy. 87 pts (69.0%) had discontinued treatment, primarily due to progressive disease (36.5%) or adverse events (21.4%). The median (range) treatment duration and follow-up from first dose to data cutoff were 8.5 (0.5-27.2) and 20.6 (5.7-34.1) months for all treated pts, and 8.4 (0.8-27.2) and 17.6 (5.7-33.1) months for the DG. The ORR (95% CI) was 75.4% (66.9-82.6) for all treated pts and 77.7% (68.4-85.3) for the DG (Table 1); CRR (95% CI) was 18.3% (11.9-26.1) for all pts and 19.4% (12.3-28.4) for the DG. Among all treated pts with complete or partial response, 73.7% of responses occurred at the first disease assessment. Median (95% CI) DOR was 14.7 (12.0-20.3) months for all pts and 14.7 (10.4-not estimable [NE]) months for the DG. Median (95% CI) PFS was 14.0 (11.3-19.6) months for all pts and 15.8 (11.0-NE) months for the DG. Median OS was not reached. Among 126 treated pts, treatment-emergent adverse events (TEAEs) occurred in 97.6% (n=123) of pts (grade ≥3 in 58.7% [n=74]). The most common TEAEs were diarrhea (38.1%), nausea (24.6%), and cough (22.2%); most common grade ≥3 TEAEs included diarrhea (11.9%) and neutropenia (10.3%). TEAEs leading to dose interruption or dose reduction occurred in 46.8% and 17.5% of pts, respectively. TEAEs led to treatment discontinuation in 23.8% of all pts; the most common were diarrhea (7.1%), colitis (4.0%), pneumonitis, and rash (2.4% each). Serious TEAEs were experienced by 45.2% (n=57) of pts overall; the most common reported among all pts were diarrhea (7.1%), colitis (6.3%), and pneumonitis (2.4%). Two pts (1.6%) overall experienced a fatal TEAE. Conclusions: Parsaclisib monotherapy demonstrated a rapid and durable response, had an acceptable safety profile, and was generally well tolerated in pts with R/R FL. These data suggest that parsaclisib could be a favorable treatment option for pts with R/R FL. Figure 1 Figure 1. Disclosures Lynch: Morphosys: Consultancy; Takeda: Research Funding; Incyte: Research Funding; TG Therapeutics: Research Funding; Rhizen: Research Funding; Bayer: Research Funding; Juno: Research Funding; Cyteir: Research Funding; Genentech: Research Funding. Avigdor: Pfizer: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; BMS: Research Funding; Janssen: Research Funding; Takeda: Consultancy, Honoraria. McKinney: ADC Therapeutics: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy; Novartis: Research Funding; Nordic Nanovector: Research Funding; Molecular Templates: Consultancy, Research Funding; Kite/Gilead: Honoraria, Speakers Bureau; Incyte: Research Funding; Genetech: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Epizyme: Consultancy; BTG: Consultancy; Beigene: Research Funding; Verastem: Consultancy. Paneesha: AbbVie: Honoraria; Bristol Myers Squibb: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Roche: Honoraria; Celgene: Honoraria. Wahlin: Gilead Sciences: Research Funding; Roche: Consultancy, Research Funding. Cunningham: Celgene: Research Funding; OVIBIO: Membership on an entity's Board of Directors or advisory committees; Bayer: Research Funding; 4SC: Research Funding; Eli Lilly: Research Funding; Clovis Oncology: Research Funding; MedImmune: Research Funding; AstraZeneca: Research Funding; Roche: Research Funding. Morley: AbbVie; Takeda: Other: Conference support; Janssen: Honoraria; Kite: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Conference support. Canales: Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Sandoz: Honoraria, Speakers Bureau; Sanofi: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy; Gilead/Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Eusa Pharma: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; iQone: Honoraria. Bastos-Oreiro: Takeda: Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Kite: Speakers Bureau; Gilead: Honoraria; BMS-Celgene: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; F. Hoffmann-La Roche: Honoraria, Research Funding, Speakers Bureau. Belada: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Celgene: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses, Research Funding. Zheng: Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. DeMarini: Incyte: Current Employment, Current equity holder in publicly-traded company. Jiang: Incyte: Current Employment, Current equity holder in publicly-traded company. Trněný: Gilead Sciences: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Amgen: Consultancy, Honoraria; 1st Faculty of Medicine, Charles University, General Hospital in Prague: Current Employment; Celgene: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Investigational PI3K delta inhibitor (parsaclisib) for patients with FL

Abstract: Abstract 3557 Introduction: Autologous stem cell transplantation for patients with amyloidosis results in high reported hematologic and organ response rates compared with conventional chemotherapy. Patients: Four-hundred and thirty-four patients have undergone transplantation between March 8, 1996, and April 13, 2010 Table 1. Clinical parameters seen in patients with amyloid are given in Table 2. The overall day-100 mortality seen in this group of patients is 44 of 434 patients (10%). Results: The most important determinant of outcome is stage defined by BNP and troponin levels. Figure 1 demonstrates the survival for patients for all 3 cardiac stages. Troponin 〈 .035; NT-proBNP 〈 332. Stage 1 both low, Stage 3 both elevated. The survival of all patients based on whether they achieved a complete response, a partial response ( 〉 50%), or no response was analyzed. Median survival has not been reached for the complete response group, is 107 months for the partial response group, and is 32 months for the no response group (p 〈 0.0001). Figure 2, divides the patients at the median dFLC level of 13.5 mg/dL demonstrating that for patients with a higher level of free light chain, the median survival is 87.6 months and has not been reached for those with a lower level of free light chain. A proportional hazards model for variables that impact on survival was done in all patients, and the only relevant predictor of outcome was stage (p 〈 0.0001). When the same analysis was performed using a landmark of 6 months, the only predictor of outcome was stage (p=0.0005). When best response was incorporated into the landmark model, it was the strongest predictor of survival. The amyloid stage predicted survival (p= 0.0005), and the best response to therapy (p 〈 0.0001). When the same analysis was performed in the entire group of 434, stage and best response each remained significant (p 〈 0.0001). Discussion: There is a high response rate associated with high-dose therapy that was not observed in the melphalan and prednisone era. For eligible patients who can be transplanted safely, high-dose melphalan is an effective therapy for many patients with amyloidosis. Best response and stage at diagnosis are the best predictors of overall survival. Disclosures: Lacy: Celgene: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

Abstract: Abstract 600 Background: Both MM and AL are plasma cell neoplasms. The underlying clone in both diseases appears to be different not only in terms of “tumor burden” but also in terms of their underlying biology. The overall “fitness” of patients with these two diseases is also different, with AL patients having more major organ dysfunction. Therapy for both diseases is directed at killing the underlying clone. ASCT is one method of reducing the clone size and thereby improving overall survival. Post-ASCT outcomes between the two diseases have never been formally compared. Methods: We compiled all patients with a diagnosis of AL or MM who received ASCT at the Mayo Clinic Rochester between June 1996 and January 2011 to compare outcomes. Patients were retrieved from two prospectively maintained clinical transplant data bases (M.A.G.). Differences between groups were compared using Fisher's exact and Wilcoxon tests. Survival was calculated using the method of Kaplan-Meier, and differences between survival outcomes were calculated by log rank. Cox regression modeling was done to determine how non-disease specific variables—i.e. age, time period of ASCT, number of prior regimens, time to ASCT from diagnosis and acquisition of complete response (CR)—affected outcomes. All statistical analyses were performed using JMP (SAS, NC) software. This study was approved by the Mayo IRB. Results: The data set was comprised of 454 patients with AL and 1116 patients with MM. There were significant differences between the two respective groups of patients in terms of number of prior regimens (0 vs 1, p 〈 0.0001), time to ASCT (3.95 months vs 7.20 months, p 〈 0.0001), intensity of conditioning regimen (non-attenuated in 69.4% vs 89.1%, p 〈 0.0001), serum creatinine (1.1mg/dl vs 1mg/dl p 〈 0.0001), creatinine clearance (72.5 ml/minute vs 80 ml/minute p 〈 0.0001), albumin (2.61g/dl vs 3.50g/dl, p 〈 0.0001) CRP (0.40mg/dl vs 0.63mg/dl p 〈 0.0001), LDH (196 U/l vs 182U/l, p 〈 0.0001), and bone marrow plasmacytosis at transplant (6% vs 9%, p 〈 0.0001). Hematologic response rates were also significantly different between the groups, with higher overall hematologic response in the MM group (90.9% vs 79.5%, p 〈 0.0001) and higher complete response (CR) rates (40.1% vs 29.4%, p 〈 0.0001) in the AL group. With a median follow-up of surviving patients of 68 months, the respective median overall survival (OS) for the AL and MM patients was 113 and 59.5 months, p 〈 0.0001. Notably, the 5-year OS of AL and MM patients achieving CR were 91.4% and 57.7%, respectively, p 〈 0.0001. If only those patients who were transplanted within 1 year of their diagnosis are included in the analysis, the respective 5-year OS of AL and MM patients achieving CR were 90.4% and 61.3%, p 〈 0.0001 (Figure 1). To correct for imbalances in non-disease specific parameters, 3 multivariate analyses were performed using: 1) all patients; 2) only those achieving CR; and 3) only those who achieved a CR and were transplanted within 12 months of their diagnosis (Table 1). Among those patients achieving CR, MM patients had nearly a 4-fold risk of death as compared to patients with AL. Conclusion: Although ASCT is not available to all patients with either AL or MM, there is a significant difference in outcomes based on the diagnosis. Patients with AL who undergo ASCT enjoy a superior survival as compared MM patients undergoing the same procedure. This difference is most notable among those patients who achieve CR suggesting very different plasma cell biology between the two diseases. Disclosures: No relevant conflicts of interest to declare.

Abstract: Introduction: The Bone Marrow Transplant Program at Mayo Clinic (Rochester, Minnesota) developed a multidisciplinary approach (involving physicians, nurses, pharmacists, dietitians, and financial specialists) for outpatient management of patients undergoing stem cell transplantation. This approach uses an electronic ordering system for diagnostic tests and chemotherapy to minimize medical errors. Table. Patient Characteristics (N=716) Characteristic Value Male, no. of patients (%) 426 (59) Age, median (IQR), y 59 (53–65) Creatinine, median (IQR), mg/dL 1.0 (0.9–1.2) b2-Microglobulin, median (IQR), mcg/mL 2.5 (1.9–3.7) Gammopathies, no. of patients (%) Measured by serum immunofixation or immunoelectrophoresis IgA 148 (21) IgG 414 (58) IgM 6 (1) IgD 12 (2) Light chain 83 (12) Biclonal 6 (1) None 47 (7) Measured by urine immunofixation or immunoelectrophoresis k light chain 402 (56) l light chain 226 (32) Biclonal 1 (0) None 79 (11) Not performed (anuric) 8 (1) Status at stem cell transplant, no. of patients (%) Untreated 4 (1) Plateau 436 (61) Primary refractory 113 (16) Relapse after therapy 93 (13) Relapse during therapy 70 (10) Characteristic Value CD34+ cells, median (IQR), ×106/kg Collected, no. 10.0 (7.6–12.6) Infused, no. 4.7 (3.9–6.2) Sessions of apheresis, median (IQR) 3 (2–5) Engraftment, median (IQR), days after transplantation Neutrophils, 0.5×109/L 13 (12–15) Platelets, 50×109/L 16 (14–22) Duration of hospitalization, median (IQR), d 4 (0–10) Abbreviation: IQR, interquartile range. Results: During a 45-month period after implementation of the program (2005-Sept 2007), the day-100 survival rate was 99.5% for low-risk myeloma patients (transplantation during first plateau; n=202) and 97% for high-risk myeloma patients (refractory, relapsing or second or greater plateau; n=71). The overall day-100 survival rate was 99%(270/273). Analysis of hospitalization trends since inception of the program showed that 39% of patients completed the transplant procedure as outpatients. The median duration of hospitalization for all patients was 4 days; age and serum creatinine levels were predictive of the need for and duration of hospitalization Conclusion: Outpatient stem cell transplantation is feasible for patients with multiple myeloma with a therapy mortality of 1%. Nearly 40% of our patients completed the procedure without hospitalization. Age and serum creatinine levels predicted a higher likelihood of hospitalization. Implementation of out patient transplant requires affordable housing in the community since many third party payers do not support hotel costs despite the reduction of hospital days. The hospital physical plant and patient registration process has to support use of designated hospital rooms for purely out patient practice. The transplant team must have process owners to standardize across all disease categories collection protocols, conditioning regimens, infusion SOP’s and post infusion supportive care guidelines for standard antibiotics, narcotics, laboratory work and transfusion thresholds. A care team meeting between physicians, nursing, dietary, pharmacy, business office, data base and appointment coordinators is essential to coordinate all the multidisciplinary efforts. Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of age greater than or less than or equal to 65 years Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of age greater than or less than or equal to 65 years Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of creatinine greater than or equal to or less than 1.5mg/dL Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of creatinine greater than or equal to or less than 1.5mg/dL

Abstract: Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies.

Abstract: Abstract 3095 Background: Although HDM is the standard conditioning for pts with MM undergoing ASCT, it is not sufficient for cure. In an effort to improve upon this standard, we added escalating doses of Y-90 Zevalin (a murine IgG1 kappa monoclonal antibody Ibritumomab conjugated to Y-90) to HDM in a standard 3+3 phase I trial design. Y-90 is a beta-emitting radioisotope with a path length of 5 mm allowing it to target CD20+ cells and bystander cells within 5 mm. Methods: Eligibility included being a candidate for ASCT. Consenting patients (pts) received: day -22, rituximab 250 mg/m2 with In2B8 for scanning; day -14, rituximab 250 mg/m2 with escalating doses of Y90-Zevalin; day -2 and -1, melphalan 100 mg/m2/day; day 0, at least 2 × 10(6) CD34/kg stem cells; and GM-CSF until ANC engraftment. The 6 dose levels (DL) were (in Gy): 10; 12; 14; 16; 18; and 20. Dose limiting toxicity (DLT) was defined as: sustained pulmonary or liver toxicity (grade3; 96 hours duration or VOD that does not resove by day 30); delayed engraftment (ANC 〈 500 at day 21 or platelet transfusion dependence at day 35); and non-hematologic grade (gr) 4 toxicity excluding gastrointestinal or constitutional. Responses were according to IMWG criteria. Accrual was between May 2005 and June 2011. Data was frozen as of August 2, 2011. Results: Thirty pts have been accrued: DL1, 3; DL2, 3; DL3, 3; DL4, 6, DL5, 6; DL6, 6. The median age of patients was 59 (range 32, 73), and 70% were male. 60% had ASCT as primary therapy. The other patients were transplanted in chemosensitive relapse (n=3), chemoresistant relapse (n=7), and untested relapse (n=2). Median time from diagnosis to protocol therapy was 10.4 months (range 3.5, 94.3). Five pts had prior radiation therapy, and 11 had prior ASCT. Maximum tolerated dose (MTD) of Zevalin with fixed dose melphalan 200 mg/m2 was DL 5 (18 Gy) which amounted to 168 mCi (124, 182) administered. No DLTs were observed at DL 1, 2, 3, or 5. There was 1 DLT at DL 4, comprising hepatic failure (gr 5) CMV viremia (gr 3), and delayed engraftment, in a 73 yo patient with chemoresistant relapsed disease, and 2 DLTs at DL 6. These DL 6 DLTs included: 1) fatal bowel necrosis (day 12 post ASCT) in a 67 yo patient with relapsed refractory MM and history of CAD, ischemic colitis, DM; and 2) fatal biopsy proven venoocclusive disease (gr 5), which began day 91 post ASCT in a 62 yo patient with primary refractory MM, peri-mobilization S. aureus bacteremia with septic embolic, and line associated venous thrombosis. Overall, gr 3 or higher AEs were observed in 100% of pts. Non-heme gr 4 AEs were seen in: DL1, 1; DL2, 2; DL3, 0; DL4, 1; DL5, 0; DL6, 4. Median time to ANC 〉 =500 and plts 〉 =50 was 11 (range 8, 17) and 15 days (range 11, 89). Confirmed response rates from immediately pre-protocol to best confirmed response were: CR, 5; VGPR, 5; continued VGPR, 4, and continued PR, 7. If one includes best confirmed response from baseline for those patients using transplant as primary consolidation, 4 PRs are upstaged to VGPRs. Median follow-up for all pts is 24.5 months (0.8, 64.8), and 10 pts have died. The median PFS for pts proceeding to early and delayed ASCT was 30.4 months (95%CI 4.1-NR) and 10.3 months (95%CI 2.8–21.7), respectively. The median OS for pts proceeding to early and delayed ASCT was not attained and 11.4 months (95%CI 2.8-NA), respectively. Conclusions: For patients with multiple myeloma, the MTD of Zevalin with fixed high-dose melphalan is 18 Gy. The combination of a VGPR plus continued VGPR rate of 60%, a median PFS of 13.1 months, and a 73% 1 year OS rate make this a regimen worthy of further study. Disclosures: Kumar: Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees.