ALBERT

Description: Abstract 4534 Background: Linezolid is an oxazolidinone antimicrobial often used to treat resistant gram-positive bacteria. Linezolid has been associated with mild, reversible, time-dependent myelosuppression, including thrombocytopenia, anemia, leukopenia, and pancytopenia. The hematologic effects most commonly reported are thrombocytopenia and anemia. In general, these effects have occurred with treatment durations of ≥ 14 days. Patients with underlying hematologic abnormalities may be more at risk for the development of linezolid-induced myelosuppression, but this is controversial. We hypothesized that use of linezolid before engraftment may delay hematopoietic recovery following stem cell transplant (SCT), and performed a matched controlled analysis to investigate this hypothesis. Methods: With approval from our institutional review board, we retrospectively evaluated 24 patients who received linezolid and compared them to 60 controls who did not receive linezolid from 1/1/1997 to 1/1/2010. Our SCT database was utilized to find matched controls and matching was based on the following: diagnosis; transplant type (autologous, matched sibling, matched unrelated, cord blood); cell source (peripheral blood, bone marrow, cord blood); transplant conditioning regimen; and age within 10 years. Patients then underwent further screening for study enrollment. Patients in the linezolid group were included if linezolid was administered at any time from the stem cell infusion (day 0) through engraftment of white cells but for a duration of at least 72 consecutive hours. Patients 1 year of age or older were included. The data were analyzed for the effects of linezolid on time to neutrophil (first of 3 consecutive days in which ANC 〉 500) and platelet engraftment (first of 7 consecutive days in which platelet count was〉 20,000 without transfusion), and the cumulative incidence of engraftment of both neutrophil and platelets within the first 100 days post-transplant. We also studied the subgroup of controls that received vancomycin to treat gram-positive infections. Results: The linezolid and control groups were similar with respect to age (median 44 vs. 41 years), gender (50% vs. 58% male and 50% vs. 42% female) disease type (29% vs. 25% had AML or MDS), cell source (67% vs. 63% apheresis product), transplant type (67% vs. 63% allogeneic), ablative vs. non-ablative conditioning (79% vs. 83% myeloablative), and cell dose (median CD34 dose 4.52 × 106/kg vs. 4.34 × 106/kg). Table 1 shows engraftment data. The median time to engraftment (ANC plus platelets) for linezolid group vs. control group was 50 days (11 patients censored) vs. 15.5 days (10 patients censored). With regard to engraftment failures, 16% of patients in the linezolid group vs. 7% in the control group failed to reach ANC 〉500. Forty-six percent of patients in the linezolid group vs. 13% in the control group failed to achieve platelet engraftment 〉20,000. Figure 1 shows overall survival. Day 100 survival rates: 58% for the linezolid group vs. 92% for controls. The cumulative incidence of engraftment of both neutrophils and platelets (using death without engraftment as the competing risk) was significantly lower in the linezolid group (54%) compared to the control group (83%) (p=0.005) Conclusions: Linezolid does not significantly affect time to neutrophil engraftment, but it does appear to significantly prolong time to platelet engraftment when compared to patients who did not receive linezolid. Linezolid should be used cautiously early after stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

Description: Key Points BFR is an effective allogeneic conditioning for chronic lymphocytic leukemia/lymphoma. Remarkably, this BFR regimen resulted in a low incidence of myelosuppression and severe acute GVHD.

Description: Abstract 894 Background: We previously reported the use of fludarabine, cyclophosphamide and rituximab as a nonmyeloablative allogeneic conditioning for CLL and non-Hodgkin's lymphomas (Khouri et al, Blood 2008;111:5530). Bendamustine is a novel compound which was found to be effective in pts who were refractory to alkylating agents. In order to improve outcomes in nonmyeloablative stem cell transplantation (NST), we substituted cyclophosphamide with bendamustine in the conditioning. Methods: Bendamustine was given iv in an escalated dose of 70, 90, 110, 130 mg/m2 daily on days −5 to - 3 prior to NST, together with 30 mg/m2 of fludarabine given on the same days. Rituximab was given at a dose of 375 mg/m2 on day –13 and 1000 mg/m2 on days −6, +1, and +8, as previously described. Tacrolimus and methotrexate was used for GVHD prophylaxis. In addition, thymoglobulin of 1 mg/kg was given on days −2, and −1 in pts receiving an unrelated donor. Results: The study included 23 pts [Mantle cell=9, CLL=6 (2 with 17p- and 1 Richter's), Follicular =4, Diffuse large cell =3]. All pts had relapsed disease after the best conventional therapy (-ies) available. Median age was 60 (range, 30–70) years. Median prior treatments was 2 (range, 1–5); 3 pts (13%) had failed a prior autotransplant. At NST, 11 pts (48%) were in CR, 7 (31%) in PR, 1 (4%) induction failure/sensitive, and 4 pts (17%) had refractory disease. Fifteen pts (65%) received their transplants from HLA-compatible siblings and 8 (35%) from unrelated donors. Continual Reassessment Method based on target toxicity at day 30 post NST was used for dose finding. The number of pts who received the 70, 90, 110, 130 mg/m2 daily doses of bendamustine were 2, 3, 3, and 15 pts, respectively. No dose-limiting toxicity was observed. Fourteen pts (61%) did not nadir to an ANC〈 500; 3 pts did not require neupogen for ANC recovery; 19 (83%) did not experience a platelet count 〈 20,000/mm3. All pts engrafted donor cells. Median donor T cells at day 30 was 93%. Only one pt developed acute GVHD (it was grade 3); none had acute grade 2 or 4. Chronic extensive GVHD was observed in 2 of 22 (9%) evaluable pts. Fungal infection was the cause of the only death observed. Twenty pts (87%) achieved CR, 2 (9%) have ongoing PR, and 1 (4%) had SD. With a median follow-up time of 8 months (range, 3–25 months), the OS and PFS rates were 92% and 79%, respectively. Conclusions: Our results represent the first report to suggest that combining bendamustine at a dose up 130 mg/m2 daily × 3 days, together with fludarabine and rituximab is safe and constitutes a well tolerated conditioning for NST. We are treating pts with this regimen in the outpatient setting. The study is currently ongoing to assess its efficacy in a larger cohort of pts. Disclosures: Khouri: Cephalon: Research Funding. Off Label Use: Bendamustine use in SCT.

Description: Most common cutaneous T-cell lymphomas (CTCL) are Mycosis fungoides (MF) and a leukemic, erythrodermic (E) variant known as Sézary Syndrome (SS). Blood (B) criteria were not previously considered for staging purposes and are evolving. E-CTCL can be divided into E-MF versus SS based on new criteria, B0-B2, published by the ISCL guidelines. Historically, overall survival (OS) of “SS” patients is 2–4 years. To determine if hematologic staging and prognostic variables affects overall survival, we retrospectively studied 1197 MF/CTCL patients seen at MDACC since 1987 from which were identified 124 (10%) patients with E-CTCL. Median age at diagnosis was 63 (range 0–89), 71 males and 53 females. Hematologic (H) stage was based on quantitative Sézary cell counts (manual or by flow as absolute CD4+26−). Overall survival curves were estimated by Kaplan and Meier and compared using log-rank tests. Median OS all 124 E-CTCL patients was 5.1 years [range=0.4–18.6]. We also considered patients divided by the H0–H4 staging system (Russell-Jones 2000). For H0–H2, OS was 7.6 years, H3 was 5.4 years, and H4 was 2.4 years (p=0.011). Treatment with systemic steroids, advanced age, increased serum LDH at presentation, WBC 〉 20,000 were significant prognostic factors. Large cell transformation (p=0.758), positive T-cell receptor gene rearrangement in the skin (p=0.54), stage of disease (p=0.955), prior exposure to multiple treatments (p=0.953), and CD4:CD8 ratio (p=0.068) were not significant. In conclusion, we provide evidence that absolute Sézary cell counts can be used to define three groups of patients with E-CTCL with different overall survival patterns and propose a modification to the ISCL B ratings as follows: B0, absolute Sézary cell count 〈 1.0 KuL−1; B1: absolute Sézary cell count ≥ 1.0–10.0 KuL−1; and B2: absolute Sézary cell count 〉10.0 KuL−1. Serum LDH and CD4/8 ratio may be used to estimate tumor burden, as they correlate with Sézary counts.

Description: Multiple myeloma is a plasma cell dyscrasia that accounts for approximately 10% of all hematologic malignancies. In the past, high-dose chemotherapy followed by autologous stem cell transplant in multiple myeloma patients has been shown to be superior to conventional chemotherapy. Melphalan, given at a high-dose of 200mg/m2 intravenously, has been established as the most effective preparatory regimen for patients with multiple myeloma. At M.D. Anderson Cancer Center, the standard-of-care preparatory regimen in patients with multiple myeloma receiving an autologous stem cell transplant is melphalan 200 mg/m2 given over two days with one day of rest prior to transplant. Other treatment schema that have been shown to be efficacious in this population include the administration of melphalan 200 mg/m2 over one day with one day of rest prior to stem cell transplant or melphalan 200 mg/m2 over two days with no rest prior to stem cell transplant. The primary objective of this study is to determine if differences exist in the severity of toxicities and treatment-related mortality in patients with multiple myeloma who receive melphalan as a preparatory regimen in three distinct treatment schema. The secondary objective of this study is to ascertain the differences in time to engraftment in this population. Toxicities, defined as nausea, vomiting, diarrhea, renal and hepatic dysfunction, were graded utilizing the NCI-CTCAE. Pain secondary to mucositis was recorded based on utilization of patientcontrolled analgesia (PCA). We hypothesized that no differences existed between the three treatment schemas with respect to the primary and secondary endpoints. We performed a retrospective chart review in Stem Cell Transplant patients with multiple myeloma who received one of the following preparatory regimens: arm melphalan 200 mg/m2 over days -3 and -2, arm melphalan 200 mg/m2 over day -2, or arm melphalan 200mg/m2 over days -2 and -1. This retrospective review included multiple myeloma patients over the age of 18 in first remission or with primary refractory disease who received autologous transplantation within 12 months of diagnosis. Patients who received prior transplantation were excluded from this review. One hundred and sixty-five patients were identified from the institutional Stem Cell Transplant database and patients were selected at random for subsequent data collection. Data for 100 patients are included in this interim analysis. The majority of patients identified in this review were male, under the age of 65, International Staging System stage of I–II, and had an ECOG performance status of 0–1. With respect to the primary endpoint, no statistically significant differences were observed in the severity of toxicity when comparing the three treatment schemas (nausea: p= 0.55; vomiting: p= 0.46; diarrhea: 0.52, Kruskal-Wallis test and PCA use secondary to mucositis: p= 0.82, Fisher’s exact test). Furthermore, there was no evidence of treatment-related mortality in all arms. With regard to time to engraftment, the actual difference between the arms was approximately 1 day, yet the comparison between the three groups was statistically significant (p

Description: Background: The addition of R has been shown to improve results for pts with relapsed DLBCL who undergo BEAM (carmustine, etoposide, cytarabine, melphalan) high-dose chemotherapy followed by an autologous stem cell transplantation (ASCT) (Khouri IF, J Clin Oncol 2005;23;2240). The incorporation of radiolabeled antibodies such as yttrium-90 ibritumomab tiuxetan to conditioning regimens has also been evaluated without additional toxicity (Khouri IF, ASH 2007, abstract 620). Subsequently, a randomized trial which was undertaken at our center to compare these 2 regimens was closed early because of slow accrual. Herein, we compare the long-term outcome in pts treated in these trials. Methods: A combined analysis was carried out from 113 pts. Between 1999 and 2003, 57 pts with relapsed DLBCL were enrolled on a protocol with BEAM conditioning plus R at 1000 mg/m2 on days +1 and +8 after ASCT (Group A). Between 2004 and 2006, a similar group of 26 patients were entered onto a trial consisting of ibritumomab tiuxetan plus BEAM (Z/BEAM). Ibritumomab tiuxetan was given at the fixed doseof 0.4 mCi/Kg on day -21 followed by BEAM(days -7 to -1) (Group B). In 2007-2010, a randomized trial was undertaken comparing BEAM/R (Group C, n=16) and Z/BEAM (Group D, n=14). All pts received R during stem cell collection, administered at 375 mg/m2 on the day before initiating chemotherapy for stem cell mobilization, and again at 1000 mg/m2, 7 days later. The same eligibility criteria were used for all groups. In addition, pts who were enrolled on the randomized trial (Groups C and D) underwent FISH analysis for -5 and -7 and cytogenetic analysis by G-banding pre-enrollment; those who had a clonal abnormality were excluded. We also retrospectively evaluated the histologic subtypes of mediastinal, transformed and de novo DLBCL. We determined the cell-of-origin of the latter using the Visco/Young and Choi W, et al. immunohistochemical algorithms. A univariate analysis was conducted for factors of interest: this included the group conditioning, age, sex, number of prior treatments, disease status at transplantation (CR/PR), IPI (0 vs 〉0), LDH, β2-microglobulin, PET status, and histology subtype. Multivariate survival analysis was then conducted using backward elimination on the basis of the likelihood ratio test and including the conditioning regimens and all the factors with P 〈 0.05 in the univariate analyses. Patients: There was no significant difference in the prognostic factors described above between the 4 groups with the exception of prior treatments. More pts in the BEAM/R groups received 〉 2 prior chemotherapies than the Z/BEAM groups (32%, 11.5%, 69% and 50% in Groups A, B, C and D, respectively; P 〈 0.001). Non-GCB histology within the 4 groups was present in 39%, 26%, 31% and 21%, respectively (P=0.31). Results: The median follow-ups times for Groups A, B, C and D were 11.8, 8.1, 4.2 and 4.9 years, respectively. The 5-year overall survival (OS) rates for these groups were 74%, 73%, 69% and 86%, respectively (P = 0.46) and the disease-free survival (DFS) rates were 62%, 65%, 63%, and 63%, respectively (P = 0.99) (Figure 1). Multivariate analysis at 5-year showed that previous exposure to 〉3 prior chemotherapies and IPI were predictors for OS (P= 0.003 and 0.005, respectively), and DFS (P = 0.003 and 0.006, respectively). There was no significant difference in OS or DFS rates between GCB, non-GCB, mediastinal and transformed DLBCL (Figure 2). The 5-year non-relapse mortality for all pts was 4.7% and the 5-year relapse rate was 32.5% (34.0%, 30.8%. 25% and 37.5% for Groups A, B, C and D, respectively). The 5-year risk of secondary myelodysplasia (MDS) for all pts was 6.2%. None of the pts in Groups C and D who had pre-transplant cytogenetic testing developed MDS at 5-year. Conclusions: Long-term follow-up results show no difference in OS, DFS, relapse rate, or risk of MDS between Z/BEAM and BEAM/R after in-vivo purging with R during stem cell collection. Our results were reproducible in 3 trials and appear to be superior to published reports in the literature of similar trials without in-vivo purging. This highlights the importance of this procedure for ASCT in DLBCL. Figure 1. Figure 1. Disclosures Off Label Use: The use of Zevalin and rituximab in transplantation. Alousi:Therakos, Inc: Research Funding. Fanale:Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Research Funding; Infinity: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Genentech: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Molecular Templates: Research Funding; ADC Therapeutics: Research Funding; Onyx: Research Funding; Gilead: Research Funding. Nastoupil:AbbVie: Research Funding; Janssen: Research Funding; Celgene: Honoraria; TG Therapeutics: Research Funding; Genentech: Honoraria. Westin:Spectrum: Research Funding.

Description: Background: Prevention or treatment of relapsed lymphoid malignancies after SCT requires novel strategies. We previously reported on safety and early responses of ipilimumab combined with lenalidomide in 16 treated patients (pts.) (Khouri et al. Clin Cancer Res, 2018). Here, we update the published data on a larger cohort of pts. with a longer follow-up. In addition, we define immune phenotpyes that correlated with response. Patients andMethods: Pts. with lymphoma or CLL who relapsed after alloSCT, with no active GVHD were eligible. Pts. with autologous SCT were included within 6 mos post-SCT if they were still in CR, but had high risk features for relapse. Treatment consisted of 4 total cycles of lenalidomide 10 mg PO daily for 21 days (cycles 1 and 3) alternating with ipilimumab 3 mg/kg IV on day 1 (Cycles 2 and 4). Considering the favorable safety profile in the initial patients treated, number of cycles was amended to 8 cycles in 6/2017. PBMC's from 20 pts (12 responders and 8 non-responders) were analyzed by flow cytometry. Results: Twenty-two pts. were enrolled. Autologous group (n=11): Median age was 57 yrs (range, 33-68). Histologies included diffuse-large-B-cell lymphoma (DLBCL) [n=6; including 3 with double-hit lymphoma (DHL)], mantle cell lymphoma (MCL) (n=2; one with CNS involvement), Hodgkin's disease (n=2; with persistent PET+ post-SCT), and follicular lymphoma (n=1, PIF with response to 4th line of therapy). Median time to enrollment after SCT was 3.8 months (range, 1.4-5.5). With a median follow-up duration of 23.4 months (range, 10.1- 48), median OS was not reached. Three pts. relapsed at a median of 6.7 months; 1 pt. died after developing T-cell lymph proliferative disorder 2 years after finishing treatment and ten pts. remain alive. The most common other AEs were 19 events of neutropenia (n=5, gr 4; n=2 gr 3, n=12 gr 2), two patients had thrombocytopenia gr 2, and one developed pulmonary embolism. All AEs resolved. An immune-related AE occurred in one patient (dermatitis, gr 3) after the second ipilimumab dose and resolved with steroids. AEs were similar in pts. who received 4 or 8 cycles (n=5). Allogeneic group(n=11): Median age was 55 yrs (range, 44- 66). Histologies included [Follicular (n=2), CLL (n=3), MCL (n=2), DLBCL (n=3; 2 of whom were DHL), and T-cell anaplastic lymphoma (n=1)]. Median number of therapies excluding the alloSCT was 3 (range 2-7). Two failed a prior autoSCT, one had 2 prior alloSCT, and three failed prior donor lymphocyte infusions, and one CLL pt. failed prior FCR, lenalidomide/ofatumumab, ibrutinib, idelalisib, CAR-T cell and venetoclax. Two pts. relapsed within 3 mos of their alloSCT prior to enrollment on study. One pt. was taken off study after cycle 1 of lenalidomide due to flare of previously diagnosed liver and skin GVHD, which responded to steroids. Another pt. developed chronic GVHD after cycle 4 which precluded treatment with the pre-planned 8 cycles. No other cases of GVHD were noted. ORR rate was 73%. Five (45%) pts. had CRs (four of which were durable at 14+, 32+, 33+ and 34+ months; including the CLL pt. who failed small molecule inhibitors and CAR-T), and 3 (27%) had PR. With a median follow-up time of 30.8 mos (range, 3-45.1), 9 (82%) pts. remain alive. One PR pt. died secondary to cardiac complications after a hip replacement; and 1 died of progression. AEs included eight episodes of neutropenia (n=2, gr 4; n=2, gr 3; n =4, gr 2), anemia gr 2 (n=1), thrombocytopenia gr 2 (n=1), diarrhea (gr 2; n=1), nausea (gr 2, n=1), headache (gr 2; n=1), hypertension (gr 2; n=1), hypoalbuminemia (gr 2; n=1). All AEs resolved. Immune monitoring of 20 transplant pts showed a Th1 type anti-tumor immune response in responding pts. In the responders, there was a higher frequency of CD4+ICOS+PD-1+ and CD8+PD+1 T effector cells at baseline when compared to non-responding pts. In contrast, the non-responders had a Th2 type response with a higher frequency of CD4+GATA3+ T effector memory cells at baseline when compared to responders (Figure). Conclusions: Follow-up results demonstrate better than expected response rates that are durable in pts. with lymphoid malignancies who relapsed after alloSCT. Continuous remission duration was also observed after autologous SCT. Immune monitoring analysis suggests that CD4+GATA3+ T cells could be a potentially valuable biomarker for stratification of pts. for lenalodimide+ipilimumab combination therapy. Figure. Figure. Disclosures Jabbour: novartis: Research Funding.

Description: Background: Timed sequential busulfan (TSB) with fludarabine is a promising myeloablative conditioning regimen for patients undergoing matched donor transplantation. Whether this approach can be used for haploidentical transplantation using post-transplant cyclophosphamide (PTCy) GVH prophylaxis is not known. Furthermore, usefulness if any of PTCy GVH prophylaxis in matched donors receiving TSB is also not known. To address these issues, we conducted a prospective phase II study of TSB conditioning regimen with PTCy GvHD prophylxis. Methods: Patients with hematological malignancies and adequate organ function were eligible for this study if they had 8/8 matched related or matched unrelated or a haploidentical related donor. They received a fixed dose of busulfan 80mg/m2 on day -13 and -12. Fludarabine 40mg/m2 was given on day -6 to -2 followed by busulfan dosed to achieve target area under the curve (AUC) of 20,000 μmol-min for the whole course based on pharmacokinetic studies done on day -13 and -6. Thiotepa 5mg/kg was given on day -7 to recipients of haploidentical donor. Graft-versus-host disease (GVHD) prophylaxis included cyclophosphamide 50mg/kg given on day 3 and 4 and tacrolimus. Haploidentical donor recipients and later MUD recipients received mycophenolate mofetil, in addition. Results: Forty five patients with a median age of 48 (15-65) years were enrolled. Twenty four patients had AML or MDS, 9 CML or MPD, 5 Lymphoma, 4 Myeloma and 3 ALL. Donors were matched sibling 11, matched unrelated 18, and haploidentical 16. Disease risk index was high in 13, intermediate in 27, and low in 5 patients. Sixteen patients had comorbidity score of 3 or higher. With a median follow up of 12 months (1-22), 1 year OS, PFS, NRM and relapse rates were 73% (60-88%), 68% (54-84%), 17% (5-29%), and 17% (5-29%) (Table), respectively. There were no graft failures. The median time to neutrophil engraftment was 16 days (13-39), and that of platelets (≥ 20K/µL) was 26 days (11-167). Day 100 grade II-IV and III-IV acute GVHD rates were 42% (27-57%) and 7% (95% CI 0-15%), respectively; 1-year chronic GVHD and extensive chronic GVHD rates were 11% (1-21%) and 8% (0-17%), respectively. One year OS in recipients of matched sib, matched unrelated and haploidentical donor were 89% (71-100%), 66% (45-95%), and 69% (49-96%) respectively and were not significantly different (P=0.31). Conclusion: Timed sequential busulfan with PTCy results in lower incidence of severe acute and chronic gvhd and promising overall survival irrespective of donor source. Disclosures Oran: Celgene: Consultancy, Research Funding; ASTEX: Research Funding; AROG pharmaceuticals: Research Funding. Rezvani:Affirmed GmbH: Research Funding. Shpall:Affirmed GmbH: Research Funding. Champlin:Sanofi: Research Funding; Otsuka: Research Funding.

Description: Background: Prevention or treatment of relapse after SCT for lymphoid malignancies requires novel strategies. Targeting immune checkpoints could result in lasting responses but only in few patients. Combination strategies with targeted agents, such as lenalidomide, could result in the release of tumor antigens to tumor-specific T cells. These T cells would become activated but also upregulate inhibitory checkpoints such as CTLA-4. These can be blocked with the anti CTLA-4 antibody, ipilimumab, to permit enhanced anti-tumor T cell responses (Sharma P and Allison JP. Cell 2015). In addition, the release of tumor antigens may focus the activated immune response on tumor antigens rather than self-antigens, resulting in fewer adverse events (AEs). Patients andMethods: Patients (pts.) with lymphoma or CLL who relapsed after alloSCT, with no active GVHD were eligible. Pts. with autoSCT were included within 6 months post-transplant, if they had high risk features for relapse. Treatment consisted of 4 total cycles of lenalidomide 10 mg PO daily for 21 days (cycles 1 and 3) alternating with ipilimumab 3 mg/kg IV on day 1 (Cycles 2 and 4). Lenalidomide dose reduction was permitted to 5 mg based on standard clinical practice. The primary objective was to evaluate safety and secondary objectives were to assess overall response rate (ORR) and survival. Results: Sixteen pts. were enrolled in the study. Autologous group (n=7): The median age was 55 yrs (range, 33 - 68). Lymphoma histologies included [Double-hit (DHL) (n=3), mantle cell (MCL) (n=3; including 2 with 2 prior transplants, one with CNS involvement), and Hodgkin's disease (n=1 with persistent PET+ post-SCT]. Median time to enrollment after SCT was 3.7 months. Median follow-up was 9.0 months (range, 5.3 - 27.1). All pts. remain alive. One DHL pt. transplanted during second remission relapsed at 1.6 months after just initiating cycle 2 of therapy. All others remain in complete remission (CR). The most common other AEs were 16 events of neutropenia (n=4, gr 4; n=2, gr 3, n=10, gr 2), thrombocytopenia (n=1, gr 2,) and one pt. developed pulmonary embolism on therapy. All AEs resolved. An immune-related AE occurred in one pt. (dermatitis, gr 2) after the second ipilimumab dose and resolved with steroids. Allogeneic group(n=9): The median age was 54 yrs (range, 44- 66). Histologies included [Follicular (n=3), CLL (n=2), MCL (n=2), DHL (n=1), diffuse large cell (n=1), and T-cell anaplastic lymphoma (n=1)]. The median number of therapies excluding the alloSCT was 3 (range 2- 7). Two failed a prior autoSCT, one had 2 prior alloSCT, and 3 failed prior DLIs. Two pts. relapsed within 2 months of their alloSCT prior to enrollment on study. One pt. was taken off study after cycle 1 of lenalidomide due to flare of previously diagnosed GVHD, which responded to steroids and pt. is now off immunosuppression. All others finished planned treatment without GVHD. ORR was 75% (CR 37.5% and PR 37.5%). With a median follow-up time of 9.2 months (range, 3.0-20.9), all pts. remain alive. Three pts. had recurrent disease at a median time of 5.4 months (range, 4.6 -12.0) after stopping therapy. One is showing ongoing response to retreatment. AEs included seven episodes of neutropenia (n=1, gr 4; n=2, gr 3; n =4, gr 2), anemia (n=1, gr 2), diarrhea (n=1, gr 2), nausea (n=1, gr 2), headache (n=1, gr 2), hypertension (n=1, gr 2). All AEs resolved. There were no immune mediated AEs. Immunologic analyses: We conducted 17-color flow cytometric analyses on PBMC pre-, during and post-treatment time points. We observed ~1.5-2-fold increase in ICOS+ CD4+T cells after ipilimumab+lenalidomide combination therapy. We previously identified an increase in ICOS+ CD4+ T cells as a phamacodynamic biomarker of ipilimumab therapy (Ng Tang et al., Cancer Immunology Research, 2014). Although we expected significant differences in immunologic impact of ipilimumab therapy in allogeneic versus autologous transplant pts., our preliminary data indicate similar immune responses in the two groups. Conclusions:Treatment with lenalidomide and ipilimumab after SCT for pts with lymphoid malignancies has a favorable toxicity profile. Our Immunological results, together with the fact that the frequency of AEs was not different between the allogeneic and autologous arms, suggest that combination therapy with lenalidomide and ipilimumab elicits measurable immunologic changes and clinical responses without inducing GVHD. Disclosures Jabbour: ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy.

Description: Background: Nonmyeloablative allogeneic transplantation has the potential to induce long-term remissions in patients with relapsed lymphoma. However, a non-intense conditioning regimen enhances the risk of early relapse. Anti-CD20 antibody radioimmunotherapy (90YIT) delivers radiation dose not only to the tumor cells that bind the antibody but also to inaccessible neighboring cells as a result of the cross-fire effect. Thus, we hypothesized that the addition of escalated 90YIT dose to the recently published bendamustine+fludarabine conditioning regimen (Khouri et al. Blood 2014) would facilitate early cytoreduction in such patients and promote improved long-term disease control by the allogeneic graft. Organ doses from a 90YIT weight-based activity prescription (mCi/kg) vary considerably, which justifies a dosimetry-based strategy for mCi/kg escalation. Methods and patients: On days -22 and -14, rituximab was given at 250 mg/m2 preceding 111In ibritumumab and 90YIT administration, respectively. Organ dosimetric assessment was performed based on serial 111In ibritumumab whole body scanning (0, 4, 24, 72 and 144 hours) , to select from among five 90YIT mCi/kg prescriptions (0.5, 0.75, 1, 1.25 or 1.5) that would result in an estimated 10 - 12 Gy dose to the liver, lungs or kidneys. Organ dose was corrected for patient-specific mass, based on a CT volume estimate times 1.03 g/cc for liver and kidneys, and a variable specific gravity for lungs (Simon, J Clin Monit Comput, 2000). Bendamustine 130 mg/m2 plus 30 mg/m2 of fludarabine IV were given daily on days -5 to - 3 prior to transplantation. Tacrolimus and mini-methotrexate (Mycophenolate mofetil in case of cord blood transplantation) were used for GVHD prophylaxis. In addition, thymoglobulin 1 mg/kg IV was given on days -2, and -1 in patients receiving an unrelated donor transplant. Results: Twenty patients were studied. The median age was 58 years (range, 37-71). Lymphoma histologies included: indolent (n=8, 40%), diffuse large cell (n=6; 30%), double-hit (n=2; 10%) and mantle cell (n= 4, 20%). The median number of prior chemotherapies received was 4 (range, 2-7). At study entry, 8 patients (40%) were in complete remission following salvage therapy, 7 (35%) were in partial response, and 5 (25%) had refractory disease. Six of 16 (37.5%) patients tested were PET+. Dosimetry: The most exposed organ was either liver (16 patients) or lungs (4 patients). The distribution among the five 90YIT mCi/kg prescriptions (smallest to largest) was 2, 4, 12, 1 and 1, with a mean of 0.94 ± 0.23 mCi/kg. If all twenty patients were treated at 1 mCi/kg (the most common prescription), the 20 Gy limit employed for 90YIT clinical trials prior to approval would have been exceeded in only one patient for the liver (22.9 Gy) or lungs (20.9 Gy). The maximum liver and lung doses at 0.75 mCi/kg would have been 17.2 and 15.7 Gy, respectively. Transplant outcomes: Fifteen patients (75%) received their transplants from unrelated donors (including 1 mismatched and 2 cord blood), and only 5 (25%) from HLA-compatible siblings. The median number of CD34+ cells infused was 6.2 × 106/kg. Neutrophil counts recovered to 〉 0.5 × 109/L after a median of 12 days (range, 0-24 days). Platelet counts recovered to 〉 20 × 109/L after a median of 19 days (range, 9-30 days). By day 30, median donor myeloid and T-cells were 100% (range, 98-100). The cumulative incidence of acute grade 2-4 GVHD and chronic extensive GVHD were 25% (5% for acute grade 3-4) and 32%, respectively. Treatment-related mortality (TRM) rates at day 100 and 1 year after transplantation were 0% and 10%, respectively. The 2 cord blood transplants engrafted with 100% donor cells and none had GVHD. With a median follow-up duration of 14 months (range, 3-34 months), the overall survival and progression-free survival rates were 85% and 70%, respectively. No significant difference in survival or TRM could be detected by age, donor type, histology, disease status, PET status or number of prior therapies. Conclusions: Our results indicate that dose-intense 90YIT combined with fludarabine and bendamustine is a well-tolerated nonmyeloablative allogeneic conditioning for lymphoid malignancies, with promising results of engraftment, GVHD and survival. Our stratified 90YIT prescription results suggest that future studies with a fixed dose of 1 mCi/kg level without dosimetry would have an acceptable radiation risk to vital organs in this setting. Disclosures Jabbour: ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy.