ALBERT

Description: HDC and AHSCT is an effective treatment option for patients with relapsed or refractory NHL. The outcome of this treatment depends on the histological grade (indolent versus aggressive) with a well documented time dependent difference in temporal relapse pattern. We developed statistical models to describe the time dependent outcome after AHSCT based on histologic grade and other variables. During January 1993 to December 2003, 114 relapsed or refractory NHL patients were treated at single institution using high-dose BCNU 600 mg/m2, etoposide 2400 mg/m2, and cisplatin 200 mg/m2 IV over 5 days and AHSCT. Median age was 53.5 (range: 25–70) years, 78 patients had aggressive NHL and 36 indolent NHL. Immediately before transplant, 75 patients received involved-field radiotherapy (IFR) to sites of prior bulky (〉 5 cm) disease. Twenty-seven patients had mobilized stem cell transplant (13 with in vivo purging and 14 with ex-vivo purging). At a median follow up of 33 (range: 3 to 118) months, the estimated 5 year Kaplan-Meier probabilities of overall survival (OS) and DSF were 61% and 51%, respectively. DFS was similar up to about 1.2 years between indolent and aggressive NHL (Figure 1). DFS of the group who had purged stem cells was improved marginally over non-purged group. Cox proportional hazards model was used to adjust for differences in baseline characteristics between grades that might affect DFS. The proportionality assumption of Cox model was tested by adding a time-dependent covariate for each variable. This showed that the proportionality did not hold for lymphoma grade, indicating the relationship between the grade and DFS differed over time. The results of piece-wise Cox model after controlling age, IFR, purging status indicate there was no difference of DFS between the grade groups up to 1.2 years (optimal cut-off point) post-transplantation (p = 0.748). However, the relative risk for experiencing relapse after 1.2 year in patients with indolent compared with patients with aggressive NHL was 4.22 (p = 0.006) with 95% confidence interval (1.5, 11.9). Our results statistically prove the previously described biological differences in outcomes of patients with indolent and aggressive NHL following HDC. The time-dependent effect of lymphoma grade on DFS indicates the need for early (within first year) incorporation of novel therapeutic approaches, such as post-transplant immunotherapy, tandem high-dose therapy and, allogeneic transplant to generate graft-versus-lymphoma effect, in management of patients with indolent NHL undergoing autologous transplantation. Figure 1: DFS by tumor grade. Figure 1: DFS by tumor grade.

Description: TRM, drug toxicities, life-threatening infections, poor quality of life, and graft versus host disease (GVHD) are significant risks of hematopoietic cell transplantation (HCT). In addition to the risks of HCT, existence of pre-transplant comorbidities can have significant impact on transplant outcomes. A comparison of CCI and the HCT-CI revealed that HCT-CI was prognostic and better at predicting TRM and overall survival (OS). However, the HCT-CI and CCI results have been inconsistent in predicting the TRM and OS in validation studies. In subgroup analyses of a large retrospective trial, HCT-CI did not predict TRM or OS for UCB recipients. Patient heterogeneity in age, disease, disease-risk, comorbidities, and conditioning regimens may have limited validation in these UCB recipients. The design of this research was to explore whether or not the HCT-CI and/or CCI can accurately predict post-transplant outcomes in young patients with high risk hematologic malignancies undergoing uniform RIC UCB transplantation. A retrospective chart review was performed on 52 consecutive young (age 〈 55) UCB transplant recipients receiving the RIC regimen fludarabine, cyclophosphamide, ATG, and 200 cGy TBI. All patients had received cyclosporine and mycophenolate mofetil for GVHD prophylaxis. Information on pre-transplant comorbidities was obtained from the CIBMTR pre-TED form for each patient and retrospective chart reviews. Demographic information, ECOG performance status (PS), identification of comorbidities, and post-transplant outcomes were obtained. Between 2005 and 2011, 52 patients age 19 – 54 (median 38) years, 30 males (58%) and 22 females (42%), underwent RIC UCB transplantation with the above regimen. Most patients had advanced stage or high risk hematologic malignancies; 28 patients had MDS/AML (54%), 8 patients had ALL (15%), while 16 patients had other hematologic malignancies. 39 patients had a PS = 0, while 13 had a PS = 1. Half of the patients were in CR 〉 2, with the same number receiving more than 2 prior therapies. 8 patients had received a prior autologous HCT, 8 a prior allo-HCT, and one patient had failed a previous UCD transplantation. 11 patients did not achieve engraftment. Median time to neutrophil engraftment was 26 days (95% CI: 24 – 28 d) and median time to platelets engraftment was 38 days (95% CI: 31 – 45 d). No patient developed grade 4 acute GVHD. Grade 3 acute GVHD was seen in 12 / 52 patients (23%). Chronic GVHD was seen in likewise seen in 12 patients (23%). To date 16 patients (30%) have relapsed. OS was 42% and PS was 37% at one year. Median PFS and median OS were 5 months and 7 months, respectively (PFS 95% CI: 1 – 11 months, OS 95% CI: 1 – 13 months). Neither CCI, nor HCT-CI were significant predictors of OS and PFS, however the ECOG PS was significantly associated with an improved OS and PFS (Table).OSPFSN1 yr2 yrs4 yrsp1 yr2 yrs4 yrspECOG PS03946%36%21%0.02644%36%21%0.0311331%0015%00CCI≤ 23944%26%10%0.2238%26%10%0.2〉 21338%31%31%38%31%31%HCT-CI02236%31%5%0.3632%32%5%0.3211443%14%14%29%14%14%≥21643%31%31%44%31%31%TRM occurred in 18 patients (35%). Neither comorbidity indices, nor the performance status were correlated to TRM (p 〉 0.05). For ECOG PS, OR 1.6 p = 0.49, CI 0.42 - 5.93; CCI OR = 2.4, p = 0.09, CI 0.86 - 6.59, HCT-CI OR = 0.6, p = 0.46, CI 0.19 - 2.08. In a previous presentation our group concluded that CCI performs better than HCT-CI in elderly patients undergoing UCB transplant. When tested in a population younger than 55 years old though, we were unable to validate the generally accepted prognostic indices. It is unclear whether this is due to a selection bias: it appears most of the patients were essentially health from a non-hematological stand-point, and as such the “classic” cardiac or pulmonary risk factors were underrepresented. The excess TRM is likely due to the severity of their underlying disease, and the majority were in CR ≥ 2 and had received multiple previous courses of antineoplastic chemotherapy. As umbilical cord transplants become more utilized, a new prognostic index needs to be developed, more fitting to the patients 〈 55 years old. Disclosures: No relevant conflicts of interest to declare.

Description: Retrospective analyses of UCBT using early historic controls show more robust graft vs leukemia effect in recipients given two-units vs one-unit. We present herein analyses from this single institution, prospective phase II clinical trial conducted 9/2003 to 5/2008 comparing 1 vs 2 unit UCBT in patients (pts) with high-risk, recurrent hematologic malignancies treated with reduced-intensity conditioning. The number of units infused in each pt was determined by biologic assignment based on the number of cells contained in the primary unit. Pts received 1 UCB unit if the cell dose was ≥ 2.5 x 107 nucleated cells/kg recipient weight and 2 UCB units for a minimum total combined cell dose of 1.5 x 107 cells/kg recipient weight if only smaller units were available. The UCB grafts were matched at ≥ 4/6 HLA loci (antigen level matching at class I A and B loci, and allele level matching class II DRB1 loci) except for 1 pt (3/6). If 2 UCB units were used they needed to be at least a 4/6 match to each other. The conditioning regimen included: Fludarabine 35 mg/m2/d x 5 days, cyclophosphamide 1 g/m2/day x 2 days, ATG 30 mg/kg/day x 2 days and single fraction TBI 200 cGy. Thirty-seven pts, 14 females, 23 males, median age 49 (range 20–71) years were enrolled. Most pts had advanced stage or high-risk hematologic malignancies; 28 pts (76%) had MDS/AML and 9 (24%) had other hematologic malignancies. Two pts underwent 2 transplants on this study after relapsing following the first UCBT. Twenty-seven pts received 1 unit and 10 pts received 2 units. The median follow up for survivors is 17.9 (range 1.2–55.9) months (mos) and median follow up for all pts is 10.1 mos. Median time to an ANC 〉 500/μL on 3 consecutive evaluations was 24.5 (range 12–55) days and 25 (range 13–43) days for 1 and 2 units, respectively (p=0.361). Median time to platelets 〉 20,000/μL without transfusion support on 3 consecutive evaluations was 38.5 (range 24–84) days and 63.5 (range 38–117) days for 1 and 2 UCB units, respectively (p=0.009). Median event-free survival (EFS) and median overall survival (OS) did not differ comparing 1 vs 2 units: 127 (range 16–1785+) days and 216 (range 16–1785+) days for 1 unit UCBT vs 92.5 (range 27– 1545+) days and 112 (range 27–1545+) days for 2 unit UCBT. The Kaplan-Meier (K-M) OS for 1 unit UCBT was 35.6% at 4 years compared to 33.3% for 2 unit UCBT (p=0.403). No statistically significant difference in K-M 4 year EFS was seen (p=0.894). At day +100, 7 pts (26%) had progressive disease or died in the 1 unit UCBT arm compared to 5 pts (50%) in the 2 unit UCBT arm. To date 51.8% of pts in the 1 unit arm have relapsed compared to 30% in the 2 unit arm (p=0.288). A total of 15/27 pts (56%) in the 1 unit UCBT arm died and 6/10 (60%) in the 2 unit UCBT arm died. Treatment-related mortality occurred in 3/10 pts in the 2 unit UCBT arm vs 2/27 in the 1 unit UCBT arm. Chimerism analyses were performed by VNTR analyses of blood mononuclear cells to confirm donor engraftment. Ten pts failed to achieve 〉 60% donor chimerism by day T+42, 8/26 in the 1 unit arm and 2/9 in the 2 unit arm (p=0.625). One pt died in each arm prior to T+42. Primary engraftment failure was defined by failure to restore donor or pt hematopoiesis requiring UCBT with the back up graft. Notably, 4 pts had primary and 1 pt had secondary engraftment failure in the 1 unit UCBT arm while no engraftment failures were observed in the 2 unit UCBT arm. No pts had grade 4 acute GVHD and no differences for overall incidence acute GVHD were noted comparing 1 vs 2 unit UCBT. Grade 3 acute GVHD was seen in 5/26 (19%) pts in the 1 unit UCBT arm and 3/10 (30%) in the 2 unit UCBT arm (p=0.658). Chronic GVHD was seen in 3 of 23 (3 limited) evaluable 1 unit UCBT pts and 2 of 7 (1 limited, 1 extensive) 2 unit UCBT pts. Pts who received a 2 unit UCBT had increased number of CD3+ cells (p=0.011) and total nucleated cells (TNC) (p

Description: Abstract 2019 High-dose chemotherapy (HDC) followed by autologous hematopoietic cell transplantation (AHCT) has been shown to result in better outcomes than conventional salvage chemotherapy for treatment of relapsed Hodgkin (Lancet 2002;359:2065–71) and non – Hodgkin lymphoma patients (N Engl J Med 1995;333:1540–5). The relative efficacy of different conditioning regimens is still uncertain. Our center has had extensive experience with BEP, consisting of BCNU (600mg/m2), etoposide (2400mg/m2) and cisplatin (200mg/m2) (Lazarus HM, J Clin Oncol 1992;10:1682–9) with more than 150 patients transplanted using this conditioning regimen. We have observed it to be efficacious and associated with a low incidence of transplant-related mortality (Biol Blood Marrow Transplant 2005;11:13–22). The purpose of this analysis is to compare the outcomes of patients transplanted with BEP with a contemporaneous cohort of patients transplanted with BEAM (BCNU 300mg/m2, etoposide 800mg/m2, cytarabine 1600mg/m2, melphalan 140 mg/m2). We performed a retrospective analysis of 55 consecutive relapsed lymphoma patients who had either BEAM or BEP preparative therapy for AHCT between 2005 and 2010 at our institution. Given the potential for nephrotoxicity and ototoxicity of cisplatin, patients were selected to receive BEAM if they had previous renal dysfunction (any elevation of serum creatinine) or had previous hearing loss. All patients received corticosteroids for prophylaxis of BCNU – induced pneumonitis. The Mann – Whitney test was used for analysis of continuous variables, Fisher's exact test for categorical data, while survival analysis was performed with the Kaplan – Meier method. Twenty-four patients received BEAM and 31 received BEP. The median age was higher in BEAM-treated patients (51 vs. 43 years, p = 0.0392). Other baseline characteristics were comparable between both cohorts: gender (male 54 vs. 58%, p = 0.791); diagnosis (NHL 75 vs. 77.4%, p = 1.000); status of disease at transplant (partial remission or worse 33.3 vs. 35.5%, p = 1.000); median number of previous therapies (2 in both groups, p = 0.51). The rate of non-renal comorbidities was higher in the BEAM cohort, but the difference was not statistically significant (45.8 vs. 32.3%, p = 0.403). The median CD34 cell dose was similar in both groups (6.252 x106 vs. 6.475 x106 CD34 cells/μL, p = 0.842). The rate of complications, including bacteremia, other infections, mucositis, diarrhea and renal dysfunction were not statistically different (Table 1). The small sample size may have prevented us from observing a statistical difference in cardiac toxicity.Table 1.Complications observed after BEAM or BEP conditioning for Autologous Hematopoietic CellBEAM (%)BEP (%)Bacteremia45.835.5p = 0.580Non – bacteremic infections37.541.9p = 0.787Mucositis54.258.1p = 0.791Diarrhea79.164.5p = 0.370Increase in serum creatinine 〉 50%12.516.1p = 1.000Cardiac complications16.73.2p = 0.153BCNU pneumonitis4.26.4p = 1.000 The median follow up time for the whole cohort was 31 months (28 vs. 34 months, p 0.267). Relapse free survival (RFS) after 36 months was 81.1% and 82.9% for BEAM and BEP, respectively (p = 0.693) (Figure 1). Overall survival at 24 months was 89.6% for BEAM and 90.8% for BEP (p = 0.371) (Figure 2). Among patients transplanted in partial response or worse, the median RFS was 57 months after BEAM and 66 months after BEP (p = 0.3173). There were no deaths in the first 100 days after transplant for both cohorts. There were no differences in the median number of days from hematopoietic cell infusion to discharge (12.5 vs. 12.0 days, p = 0.600) or achievement of ANC 〉500/μL (10 days for both cohorts, p = 0.415). In conclusion, BEP conditioning achieved comparable engraftment, toxicity and survival outcomes to those achieved by BEAM for treatment of relapsed lymphoma patients. BEP is therefore a valid alternative for treatment of this patient population. The BCNU dose in BEP is twice that in BEAM, but we continue to observe limited rates of BCNU – induced pneumonitis. BEP may be preferable over BEAM in patients with underlying cardiac comorbidity. Longer follow up and prospective trials will help in identifying variables that aid in the selection of patients for the most appropriate conditioning regimen. Disclosures: No relevant conflicts of interest to declare.

Description: Engraftment failure and graft versus host disease (GVHD) are major obstacles to success of non-myeloablative allogeneic stem cell transplantation. Whole body UVB phototherapy has been used for the treatment of skin GVHD and has systemic immunosuppressive effects. In addition, extracorporeal photopheresis (ECP) has been used for treatment and prevention of GVHD. We hypothesized that whole body UVB phototherapy may have immunosuppressive effects similar to ECP and improve donor engraftment and reduce the incidence and severity of GVHD. The aim of this study was to test the feasibility of using UVB phototherapy initiated prior to grafting and continued until engraftment and determine its impact on transplant outcome. Eight patients median age 55.5 (range 32–65) years with hematological malignancies who were 〉55 years of age or had received prior autologous or allogeneic transplantation with myeloablative conditioning or had comorbid conditions that precluded their eligibility for myeloablative transplantation were included in this study. The graft source was matched related (n=5) or matched unrelated (n=3) donor allogeneic peripheral blood stem cells. All donors were male, median age (range) 59 (46–67) years. Conditioning regimen was fludarabine 30 mg/m2 iv for 5 days (days −8 to −4); cyclophosphamide 1 g/m2/day iv for 2 days (days −3 to −2); equine anti-thymocyte globulin (ATG) 30 mg/kg/day for 2 days (days −2 to −1). GVHD prophylaxis included cyclosporine A (CSA), methylprednisolone and escalating doses of UVB to skin tolerance 3 times a week between T-10 and T+28. The conditioning regimen and the UVB phototherapy were well tolerated. Two patients received all 14 prescribed UVB (cummulative doses 2000 and 3260 mJ) and, six patients received 8–13 treatments (cummulative dose range of 528–3465 mJ). Neutrophil (〉500ml) and platelet recovery (〉20,000/ml) occurred in median of 13 (12–17) and 6.5 days (1–35), respectively. One patient had secondary engraftment failure and another had mixed chimerism at day 100. Seven of eight patients developed severe acute GVHD, Grade III (n=5) and IV (n=2). Six had skin, 5 had GI and 1 had liver involvement. Four patients died from sepsis (n=2), acute GVHD (n=1), or chronic GVHD (n=1). The protocol was closed early due to high severe GVHD rate (87.5%, 95%CI: 60–92%) that satisfied the early-stopping rule. Four patients are alive (130–287 days), 2 without GVHD or relapse. We conclude that addition of peritransplant UVB phototherapy using the standard minimally erythemogenic protocol is detrimental to outcome of allogeneic stem cell transplantation. It is unclear how UVB phototherapy at immunsupressive doses might have altered skin and systemic cytokine and immune cell composition in the host and increased the incidence of GVHD and the treatment related mortality. Therefore although other phototherapeutic modalities may be effective against GVHD, UVB therapy is not recommended during early phases of reduced conditioning allogeneic transplantation.

Description: Introduction Umbilical cord blood transplantation (UCBT) is often complicated by delayed engraftment and higher rates of engraftment failure. We sought to investigate the outcomes of patients undergoing UCBT2 after engraftment failure compared to those who had autologous hematopoietic recovery and did not receive UCBT2. Methods We reviewed the medical records of 186 patients who received UCBT between 2001 and 2011 at the Case Comprehensive Cancer Center [Seidman Cancer Center, University Hospitals Case Medical Center and Taussig Cancer Institute, Cleveland Clinic]. Standard definitions of engraftment were used. Patients who died or had progressive disease before day 30 were excluded (n=9), as they were considered inevaluable for engraftment. Results Twenty-seven patients (15%) had primary engraftment failure; twelve had autologous hematopoietic recovery and 15 presented no recovery (Table). The median total nucleated cell dose for the first UCBT was 2.56x107 cells/kg (range 1.23 x107 - 5.69x107), not statistically different from patients achieving engraftment (p = 0.29). The cause of engraftment failure could not be identified in 22 patients. Among patients with engraftment failure without autologous recovery, 2 patients did not receive further salvage and died at 40 and 48 days after first UCBT; 2 others received backup autologous hematopoietic cell infusions and 11 received UCBT2. In patients with autologous hematopoietic recovery, 8 did not receive a UCBT2 because disease remission had been attained (n=4), active infection (n=1), relapsed disease beyond 40 days after UCBT (n=1) or absence of compatible donor (n=1). Fifteen patients (engraftment failure [n=11]); autologous recovery, [n=4]) underwent UCBT2, at a median of 43 days (range 33-244) from first to second UCBT. All patients received non–myeloablative second conditioning regimens. Four patients received one UCB unit and 11 received two units. Neutrophil engraftment after UCBT2 was observed in 10 of 15 patients at a median of 30 days (range, 13-35). The median survival for the entire cohort was 272 days (range 40–2130); one year overall survival was 36%. Engraftment and overall survival were not statistically different between those receiving 1 or 2 UCB units for UCBT2. Overall survival was not statistically different between patients who underwent UCBT2 and those who had autologous recovery or backup autologous infusions without further salvage. The proportion of patients in remission was similar in the 2 subgroups (UCBT2, 53%; autologous recovery, 50%). Relapse occurred in 2/15 patients who underwent UCBT2 and 8/10 patients who had autologous recovery or backup infusions. Forty months after transplantation, the cumulative incidence of relapse was 92% after autologous recovery vs. 50% after UCBT2 (Figure). Non–relapse mortality after UCBT2 was 73%. Conclusion Engraftment failure after UCBT frequently has no identifiable cause, and is associated with high morbidity and mortality. UCBT2 is feasible and can result in engraftment in the majority of patients, but is limited by patient condition after transplant as well as the availability of compatible grafts. UCBT2 is associated with significantly better disease control than continued autologous hematopoiesis, but additional efforts are necessary to reduce the high risk of non-relapse mortality in this group of patients. Disclosures: Hill: Celgene: Honoraria, Research Funding.

Description: Background. Ispinesib is a novel polycylic, nitrogen-containing heterocycle small molecule that acts by inhibition of the mitotic kinesin spindle protein (KSP) HsEg5. Pre-clinical studies demonstrate activity against both murine and human solid tumor and leukemia cell lines by inhibition of adenosine diphosphate release from KSP, causing monopolar spindle formation and programmed cell death. Methods. This was a single agent, phase I dose-escalation trial in patients with relapsed/refractory acute myeloid (AML) or lymphoid leukemia (ALL) or advanced myelodysplastic syndrome (MDS). Intravenous ispinesib was given for 3 consecutive days every 21 days. Doses were escalated from 1.5 mg/m2/day to 13.3 mg/m2/day in cohorts of 3 patients. Clinical and peripheral blood responses were monitored on at least a weekly basis and bone marrow evaluations were done every three weeks. Grade 3 or greater non-hematologic toxicities were considered dose limiting toxicities (DLT) with the exception of infectious complications, electrolyte abnormalities or self-limited gastrointestinal toxicities. Results. Thirty-six adults (14 women, 22 men) with a median age of 66.5 years (range 28–82 years) were enrolled. The median number of previous induction treatments was 3, with a range from 0 to 8. Two patients had MDS, 5 had ALL and 29 had AML. Patients received a median number of 1.5 cycles of ispinesib, with a range from 1 to 5. The maximum tolerated dose (MTD) was determined to be 10 mg/m2/day given on 3 consecutive days. DLTs related to the study drug were grade 3 transaminitis and hyperbilirubinemia, and these developed in a total of 6 patients; one at dose level 3 mg/m2/day, 2 at dose level 7.5 mg/m2/day and 3 at dose level 13.3 mg/m2/day. Five patients developed self-limited grade 3 mucositis at dose level 13.3 mg/m2/day. Three patients died on study. One died due to disease progression, and two died both due to infection and hepatic dysfunction. None of the patients had normalization of their blood counts. Three patients with very high peripheral blast counts had rapid clearing of the blasts during treatment. Two patients had late bone marrow responses with less than 5% blasts at dose level 10 mg/m2/day after cycle 2 and cycle 3, respectively; both subsequently died of infection without count recovery. An additional three patients had a decrease in bone marrow cellularity with persistence of leukemic blasts. Conclusions. The MTD of ispinesib in this patient population and on this schedule was higher than that observed in prior trials of non-hematologic malignancies (30 mg/m2versus 18 mg/m2). The toxicity profile was different with DLT of hepatic toxicity in this trial and DLT of neutropenia in the solid tumor trials. Ispinesib appeared to provide myelosuppression in some patients at higher dose levels; however, there appeared to be minimal effect on the leukemic marrow component. Even in the majority of patients with myelosuppression, the leukemic clone persisted and proliferated following treatment. Ispinesib was effective at clearing the peripheral blood of blasts in a minority of patients. Ispinesib, given as a single agent in this trial on this schedule, is not an effective anti-leukemic therapy.

Description: Introduction. Salvage chemotherapy followed by HDC-ASCT is considered standard of care for chemosensitive patients who have relapsed after initial therapy. CD30 is commonly expressed in Hodgkin Lymphoma (HL) and in some cases of non-Hodgkin lymphoma (NHL). Brentuximab vedotin (BV), an antibody-drug conjugate that targets CD30, induces high response rates and is now used in the salvage setting prior to HDC-ASCT. It is not clear if BV use peri-mobilization would influence mobilization and collection of autologous CD34+ stem cells. We therefore examined 42 patients who were treated with BV prior to HDC-ASCT. Methods. We retrospectively reviewed the HDC-ASCT databases of University Hospitals Case Medical Center (UHCMC) and MD Anderson Cancer Center (MDACC) and identified 42 patients who were treated with BV prior to HDC-ASCT between February 2009 and April 2014. The median age was 37 years (range, 18-67) and 52% (n=22) were male. Diagnoses were HL (n=30; 71%;), and NHL (n=12; 29%; anaplastic large cell, n=6; diffuse large B-cell, n=3; unknown subtype, n=3). Median times from diagnosis to transplant, from initial BV treatment to transplant and from last BV treatment to stem cell collection were: 21 months (range, 10-210), 5 months (range, 1.5-16.8), and 30 days (range, 2-280), respectively. Our subjects had failed multiple conventional treatments with a median of 3 (range, 2–8) lines of treatment before HDC-ASCT; 38% (n=16) received involved field radiation therapy. BV was given at 1.8 mg/kg IV every 21 days. Median number of BV cycles was 4 (range, 1-16) and the overall response rate to treatment was 71% (CR 55% + PR 16%). Thirty patients (71%) were in complete remission (CR) at the time of transplant (CR2 = 6; CR≥3 = 24), 4 (10%) were in partial remission (PR) (PR2 = 1; PR≥3 = 3), 6 patients (14%) had stable disease and 2 patients (5%) were transplanted with progressive disease. Stem cell collection target was 5 x 106 CD34+ cells/Kg. Mobilization regimens used were chemotherapy/G-CSF-based in 32 patients (76%) and Plerixafor/G-CSF-based in 10 patients (24%). Use of chemotherapy/G-CSF in first mobilization was standard at MDACC, whereas plerixafor/G-CSF was used as first mobilization at UHCMC. Results. Thirty-nine (92.8%) of 42 patients were successfully mobilized on the first attempt. Second mobilization was required in 3 cases (7.1%). Second mobilization regimens included Cyclophosphamide/G-CSF (n=2) and Plerixafor/G-CSF (n=1). The median number of infused CD34+ cells was 5.46 x106/kg (range, 1.65-54.78 x106/kg). All patients engrafted neutrophils and platelets at a median time of 10 days (range, 9-13), and 10.5 days (range, 7-35), respectively. The median time to RBC transfusion independence was 8 days (0-34). With a median follow-up of 12 months (range, 0–63), day 100 treatment-related mortality was 0%. The one-year actuarial event-free and overall survival is 50.5% and 84.1%, respectively. Conclusion. Within the limitations of this retrospective study, BV before HDC-ASCT did not adversely affect peripheral blood stem cell mobilization, collection and engraftment in a cohort of heavily pre-treated, relapsed/refractory patients with CD30+ lymphomas. Disclosures Caimi: Seattle Genetics: Equity Ownership.

Description: Abstract 3006FN2 Transplant related mortality (TRM), drug toxicities, life-threatening infections, poor quality of life, and graft versus host disease (GVHD) are significant risks of hematopoietic cell transplantation (HCT). In addition, pre-transplant comorbidities can have significant impact on the transplant outcomes of elderly patients (pts). Two comorbidity measurement tools, the CCI and the HCT-CI have been inconsistent in predicting TRM and overall survival (OS) after conventional HCT. The HCT-CI and CCI scores have correlated less well with TRM and OS in UCB transplantation. These results may have been limited by the heterogeneity of the UCB transplantation study population in age, disease, disease-risk, comorbidities, and conditioning regimens used. This study was performed to explore the accuracy of the HCT-CI and CCI in predicting post-transplant outcomes in elderly pts with high risk hematologic malignancies undergoing uniform RIC UCB transplantation. A retrospective chart review was performed on 35 consecutive elderly (age ≥ 55 years (yrs)) UCB transplant recipients receiving the RIC regimen fludarabine, cyclophosphamide, ATG, and 200 cGy TBI. All pts received cyclosporine and mycophenolate mofetil for GVHD prophylaxis. Information on pre-transplant comorbidities was obtained from each pt's CIBMTR pre-TED form and retrospective chart reviews. Demographic information, ECOG performance status (PS), identification of comorbidities, and post-transplant outcomes were obtained. HCT-CI and CCI scores were distributed in the following comorbidity risk groups 0, 1, 〉 1. Between 2002 and 2011, 35 pts underwent UCB transplantation with the above regimen. Median age was 65 yrs (range 55–71), 21 were male (60%) and 14 female (40%). Most pts had advanced stage or high risk hematologic malignancies; 28 had MDS/AML (80%) and 7 had other hematologic malignancies. All pts had a PS ≤ 2. Twenty-seven pts were in CR ≤ 2, with 31 pts having received ≤ 2 prior therapies. Eight pts had received prior transplants, including 2 pts with prior UCB transplantations and 6 pts with prior autografts. UCB cell dose was calculated on actual body weight (median 84 kg, range 56.1–135.1 kg). A total of 66 UCB grafts matched at a minimum 3/6 (3/6 = 4, 4/6 = 34, 5/6 = 22, 6/6 = 6) were infused. Pts received a range of 1 to 5 UCB units (1 unit = 12 pts, 2 units = 19 pts, 3 units = 2 pts, 5 units = 2 pts). VNTR/FISH analyses confirmed engraftment with median time of 21 days (d) (95% CI: 14–40 d) to achieve 〉 60% chimerism. Nine pts failed to achieve chimerism 〉 60%, and 3 had secondary engraftment failure. Median time to ANC 〉 500/μL for 3 consecutive values was 27 d (95% CI: 21–32 d) and median time to platelets 〉 20, 000/μL on the first day of 7 consecutive days without a platelet infusion was 40 d (95% CI: 35–71 d). No patient developed grade 4 acute GVHD. Grade 3 acute GVHD was seen in 3/35 pts (9%) and chronic GVHD was seen in 6/27 pts (22%). To date 31% (n = 11) of pts have relapsed. Pre-transplant cardiac comorbidities, A-fib/flutter and coronary artery disease, were the most common. Six pts had prior solid tumor malignancies, not active at the time of HCT, including breast (n=2), prostate (n=2), bladder (n=1), and kidney (n=1). After a median follow up of 13 months (range 1–70), 1 yr OS and progression free survival (PFS) were 61% and 55%, respectively. Median PFS and OS were both 16 months (mos) (PFS 95% CI: 8–70 mos, OS 95% CI: 9–70 mos). CCI but not PS or HCT-CI was a significant predictor of OS and PFS (Table and Figure).OS (%)PFS (%)FactorN1 yr2 yr4 yrp-value1 yr2 yr4 yrp-valuePS    0175750330.885252350.81    1-218654534584538CCI    016805822675932    14100500.04100500.04    〉115333333333333HCT-CI    012544314564415    1108069690.296969690.25    〉113533535453636 TRM occurred in 8 pts (23%). CCI was associated with TRM (p=0.05): pts with CCI ≥ 2 had a 40% (6/15) TRM vs 10% (2/20) with CCI 0–1. PS (p=0.69) and HCT-CI (p=0.47) did not correlate to TRM. In conclusion, elderly pts undergoing RIC UCB transplantation for high risk hematologic malignancies, the CCI was a statistically significant predictor of TRM, PFS, and OS. This index and not HCT-CI or PS identified elderly pts undergoing RIC UCB transplantation at higher risk of TRM and poor post-transplant outcomes. Larger validation studies of the predictive capacity of these comorbidity indexes need to be performed in the multi-institutional setting. Disclosures: Cooke: Amgen:.

Description: INTRODUCTION: Lenalidomide and Rituximab (R2) is an effective frontline treatment regimen for patients (pts) with indolent B-cell lymphoma including follicular lymphoma (FL). Recent phase III data from the RELEVANCE trial comparing R2 to traditional chemoimmunotherapy showed that this regimen is generally well-tolerated and has favorable clinical efficacy [61% overall response, 53% CR rate, 77% 3-year progression free survival (PFS) (Morschhauser, et al)]. Proteasome inhibitors such as bortezomib disrupt NF-KB signaling and have shown clinical activity in indolent NHL. Although randomized trials have failed to demonstrate clinical benefit of adding bortezomib to standard chemoimmunotherapy regimen bendamustine + rituximab (BR) for frontline treatment of FL, the addition of proteasome inhibitors to lenalidomide is a mainstay of treatment for plasma cell neoplasms due to synergistic antitumor effect. The oral proteasome inhibitor ixazomib has less potential for dose-limiting neuropathy than bortezomib, making it an attractive option to incorporate into the R2 regimen. We sought to investigate the safety and efficacy of the addition of ixazomib to R2 for FL and indolent B-cell NHL through a phase I clinical trial of this combination for patients with high risk disease. METHODS: Adult (age ≥ 18) pts with untreated FL or other indolent lymphoma, adequate organ function and performance status were enrolled. To be enrolled, FL patients were required to have stage 2, 3 or 4 disease, with high tumor burden by GELF criteria and/or FLIPI score of 3-5. During 3 x 3 dose escalation, ixazomib was given at a dose of 2 mg (n=3), 3 mg (n=3) or 4 mg (n=12) PO on days 1, 8, and 15 with lenalidomide 20 mg PO on days 1-21 every 28 days. Rituximab was administered at standard dosing on days 1,8,15,21 for cycle 1, once every 28 days for cycles 2-6 and then once every 2 months for cycles 7-12. Treatment was continued for 12 cycles and no maintenance therapy was specified per protocol. All pts received low dose aspirin for venous thromboembolism prophylaxis and acyclovir for prevention of VZV reactivation. Response assessments by CT were performed after cycle 3 and 6 and by PET/CT at the end-of-treatment (cycle 12). RESULTS: 20 pts were enrolled and 18 were eligible for treatment [15 FL (14 grade 1-2, 1 grade 3A), 2 splenic marginal zone lymphoma and 1 nodal marginal zone lymphoma].The median age of treated pts was 61 (range 40-83) years old. 55% of patients were female. Stage at diagnosis was II (n =2), III (n = 4) and IV (n = 12). For FL pts, FLIPI scores at enrollment were low (n=2), intermediate (n = 5) and high risk (n=8) and FLIPI-2 scores were low (n=3), intermediate (n = 2) and high risk (n=10). There were no dose limiting toxicities during 3 x 3 dose escalation. Grade (G) 1/2 and G3/4 treatment-related hematologic adverse events (AEs) included neutropenia (6%, 28%), thrombocytopenia (16.7%, 5.6%) and anemia (16.7%, 0%). The most common treatment-related AEs included nausea/vomiting (44% G1, 11% G2), diarrhea, (50% G1, 22% G2, 5% G3), rash (33% G1, 6% G2, 11%G3), peripheral neuropathy (22% G1, 6% G2), myalgia/arthralgia (17% G1, 17% G2), and infection (33% G2, 17% G3). There was one pulmonary embolism and no cases of febrile neutropenia. As of June, 2020, median follow-up among living pts was 21 months. 4 pts discontinued treatment due to disease progression; 2 with transformation to aggressive lymphoma. Of the transformed cases, one subject died on study due to progression disease and one developed CNS disease on study treatment but proceeded to autologous stem cell transplant. The best overall response rate was 61.2% [55.6% CR, 5.6% PR): 22.2% had stable disease and 16.7% had disease progression. 18-month Kaplan-Meier estimates of PFS and overall survival were 71% and 94%, respectively (Figure). CONCLUSION: R2 can safely be combined with at the target dose of 4 mg of ixazomib for treatment-naïve indolent NHL patients. Non-hematologic AEs were generally consistent with known toxicity of each component of therapy. CR rate and PFS were was similar to the outcomes reported in the RELEVANCE trial despite enrolling high risk patient. R2 may serve as backbone for future studies of novel treatment combinations for high risk FL after thorough evaluation for occult transformation to aggressive lymphoma. Disclosures Hill: Abbvie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding. Jagadeesh:MEI Pharma: Research Funding; Regeneron: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Debiopharm Group: Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees. Caimi:Celgene Corp: Other: Incyte Corporation - Ownership - Pharmacyclics, Inc. - Ownership - Celgene Corp. - Other, Speakers Bureau; ADC Therapeutics: Research Funding; Genentech: Research Funding. Smith:Takeda: Research Funding; Celgene: Research Funding. OffLabel Disclosure: Ixazomib is off-label for treatment of NHL