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Acute lymphoblastic leukemia (ALL) relapsing after allogeneic stem cell transplantation (allo-SCT) is usually associated with poor outcome. T-ALL patients relapsing early post-allo-SCT or relapsed B-ALL patients who have failed currently available targeted and immunotherapies need an effective salvage therapy. We herein describe 3 cases where minimal residual disease (MRD) negative remission was achieved in very high-risk relapsing ALL patients with the use of daratumumab with or without nelarabine. Patient 1: A 24-year-old male diagnosed in May 2016 with T lymphoblastic lymphoma. Following ECOG 2993-based induction, his PET became negative. Additional 3 high-dose methotrexate and 3 consolidation cycles were prescribed followed by maintenance therapy. In August 2017, he relapsed in the bone marrow (BM) and central nervous system, and a second remission (CR2) was achieved after therapy with mitoxantrone + cytarabine. He underwent allo-SCT from his matched brother in CR2. Three and a half months after the transplant he experienced a third relapse. Two cycles of nelarabine were administrated followed by daratumumab 16mg/kg in a "myeloma like" protocol. BM at the end of 2 nelarabine cycles demonstrated remission but with 0.09% residual disease cells on flow cytometry. After the first 2 months of daratumumab, BM confirmed MRD eradication. One dose of 5x105/kg donor lymphocyte infusion (DLI) was also prescribed. Patient 2: A 43-year-old female diagnosed with T-ALL in February 2017. Her disease was refractory to ECOG 2993-based induction and remission was achieved only after a second-line therapy with mitoxantrone + cytarabine. She was referred to allo-SCT from her matched sister, engrafted well and developed grade 2-3 acute graft-versus-host disease which responded well to steroids. Five months post-transplant an extra-medullary relapse was diagnosed in her eye and skin, while MRD was identified in her BM. The same regimen of 2 cycles of nelarabine followed by daratumumab 16mg/kg was prescribed. Extra-medullary disease was eliminated and so was the residual BM disease. One dose of 5x105/kg DLI was also prescribed. The case of patient 3 has just been published (Ganzel C, et al. Haematologica, June 2018). In brief, this is a 21-year-old man diagnosed 7 years ago with Ph+ B-ALL. Daratumumab was prescribed to treat his 7th relapse after he had been treated with multiple TKIs, including ponatinib, underwent two allo-SCTs and received immunotherapy with 2 different anti CD19 and anti CD22 CAR-T cell agents. In parallel to daratumumab, vincristine was administered every 4 weeks as well as daily ponatinib. Molecular remission following daratumumab was confirmed by PCR for BCR/ABL. Kinetics of response and duration of follow-up: For the patient with Ph+ ALL, daratumumab was prescribed while overt disease was present in the BM but peripheral counts were low (WBC=2,000, ANC=1,000, PLT=95,000). Hematologic remission was confirmed after 1 month and molecular remission after 4 months. Unfortunately, 6 months after the first infusion of daratumumab he relapsed again and now (one year post-daratumumab administration) he is alive and treated with bortezomib and gemtuzumab ozogamicin. Both T-ALL patients achieved morphologic remission with nelarabine and received one DLI. MRD was identified in BM examination following nelarabine cycles and its elimination was confirmed in the BM at the end of the first 2 months of daratumumab (a total of 8 weekly infusions). Currently, these patients are 20 and 22 weeks following relapse and are alive and in molecular remission. In all 3 patients we noticed no significant side effects that could be related to daratumumab infusion. Peripheral WBC and PLT count dynamics are shown in figure 1. Treatment of ALL patients who relapse with high-risk features is a great challenge. Herein we report three consecutive patients who achieved MRD negativity with daratumumab. Daratumumab can be combined with other effective agents in a simple and safe protocol that may be delivered even to heavily pre-treated patients. Although larger studies with longer follow-up are required, this novel approach may offer new hope for patients with a devastating disease such as relapsed ALL. Disclosures Ofran: Novartis: Other: Served on a Novartis advisory board.

Introduction The therapeutic options for diffuse large cell B cell lymphoma (DLBCL) patients (pts) that fail to respond/relapse after≥2 treatment regimens are limited. The SCHOLAR-1 study reported an overall response/ complete remission (ORR/CR) rates of 26%/ 7% with a median overall survival (OS) of 6.3 months in chemorefractory and early relapsing DLBCL pts. Polatuzumab vedotin (Pola) is a conjugated antibody that delivers the microtubule inhibitor MMAE to CD79b-expressing cells. Polatuzumab administered in combination with Bendamustine-Rituximab (P-BR) has been recently approved by the FDA for pts with relapsed/refractory (R/R) DLBCL that failed to respond≥2 prior therapies. The current study investigated the tolerability and efficacy of Pola mainly with BR, in DLBCL pts, treated through a compassionate program after failing ≥2 prior regimens. Methods Data of all pts with consecutive R/R DLBCL, treated with Pola-BR or Pola-R (2-8 cycles) in 11 Israeli centers between 6/2018 and -5/2019 were analyzed. Inclusion criteria for this study were: R/R DLBCL (denovo and transformed follicular lymphoma [t-FL]), age ≥ 18 years, ≥ 2 prior treatments. We evaluated pt characteristics, treatment details and toxicities, overall response and CR rates, progression free survival (PFS) and OS. Cox regression model was used to define factors affecting outcomes. Results 34 patients- (denovo DLBCL, n=24 and t-FL, n=10 ⌈50% -non CGB and 50% - GCB type⌉) were included. Median age at Pola administration was 65.5 (range 60-72) years. Stage ≥3 disease was recorded in 88% and IPI ≥3 in 73.5%. Median prior lines was 3 (range 3-5); including anthracyclines and rituximab in 100% and cisplatin-based regimens in 91%. 32% relapsed after ASCT and 9% after CART infusion. 53% had primary refractory disease, 29% had refractory relapse and 18% had prior sensitive relapse. 22 pts received Pola-B, mostly with Rituximab (n=19), and 12 received Pola-R. In 5 pts, Pola-based regimen was used as a bridge for Allo SCT (all responded CR, n=4 and PR, n=1) and in 6 as a bridge to CARTs (all responded CR n=1, PR n=2, SD n=3). Median number of Pola B cycles was 3 (3-5) and median Pola-R cycles was 4 (3-6). Median B dose per cycle was 90 mg/m2 (45-90). GCSF was used in 47%. Early treatment discontinuation due to progressive disease (PD) occurred in 8 (23%) of the entire cohort: 23% of Pola-B pts and 25% of Pola-R pts. Safety: Hematological AEs grade 3-4, reported with Pola- B vs Pola-R were: neutropenia (45.5.% vs 33%), thrombocytopenia (25% vs 8%) and anemia (23% vs 17%). Infections were recorded in 41% and 36% of Pola-B pts and Pola-R respectively. Neutropenic fever was reported in 36% in Pola-B pts and none in Pola-R. Pulmonary infections were recorded in 33.3% and 27.3% of Pola-B and Pola-R pts respectively, resulting in death in one pt. Peripheral neuropathy occurred in 18% of Pola- B pts (grade ≤2) vs 8% with Pola -R. Hospitalization due to AEs was recorded in 41% of Pola-B vs 25% of Pola-R. Pola dose reduction due to AE was reported in 1 pt (8%) in the Pola-R. Efficacy: ORR for the entire cohort was 65%, including 38% CRs and 27% PRs. 12% pts attained SD and 23% experienced PD. ORR was higher in non-GCB than in GCB pts 80% vs 43% (p=0.036). Median follow up of the entire cohort from Pola administration was 4.4 months (range 0.6-11.4). 6 months projected OS and PFS were 83% and 63%, respectively. Post Pola treatment in pts that failed to respond/Relapsed post pola: 8 patients had PD; 3 died from progression, 1-CART, 1-Allo SCT, 2-paliative care and 1-unknown. Additional 5 pts progressed during follow up; 4-CART and 1-palliative care. 1 patient continues Pola treatment after achieving SD. Univariate analysis for factors predicting PFS and OS GCB type (HR-1.816, P=0.055), Primary refractory vs relapsed disease (HR-1.507, p=0.049) and a higher number of prior lines since diagnosis (HR-1.35, p=0.079) tended to be associated with shorter time to progression. T-FL vs denovo DLBCL was associated with decreased OS (p=0.008). Data of 60 patients, including pts treated recently, therefore, not evaluable at the time of abstract submission, would be presented at ASH. Conclusions The toxicity of Pola-based regimen was relatively low. Pola based treatment provided an encouraging PFS and OS in pts with R/R DLBCL that failed to respond ≥2 prior therapies, treated in a real-life setting. Primary refractory disease, higher number prior lines and t-FL vs denovo DLBCL were associated with inferior outcome. Figure Disclosures Herishanu: Roche: Honoraria; AbbVie: Honoraria; Janssen: Honoraria.

Chimeric antigen receptor T-cells (CAR-T) are widely used for the treatment of relapsed/refractory Diffuse large B cell lymphoma (DLBCL). The data for CAR-T cell therapy in patients with extra-nodal(EN) lymphoma is restricted. We included 126 consecutive patients with DLBCL treated with commercially available CAR-T cells (tisagenlecleucel, n=100, 79.4% and axicabtagene ciloleucel, n=26, 20.6%). At lymphodepletion , 72/126(57%) had EN disease, 42/126(33%) patients had nodal disease (ND)-only and 12/126(10%) showed no disease assessed by PET-CT. There were no signi cant differences in CAR-T related toxicities and in the median PFS between EN patients and ND [10.76(95% CI: 7.8-13.6) vs 14.1 (95% CI:10-18.1) months, p =0.126)]. Similarly, median OS was not signi cantly different [15.36 (95% CI 12.5-18.2) vs. 18.4 (95% CI 14.8-22.1) months , p =0.100]. Subgroup analysis according to the number of EN involved sites showed that median PFS and OS were signi cantly higher in patients with ≤ 2 EN sites [12.3 months (95% CI 9-15.5)] vs 4.28 months (95% CI 0.6-7.9), p=0.010] compared to patients with EN sites,) vs 8.7 months (95% CI 4.6-12.8), p=0.05]. In multivariate cox regression analysis, increased number sites of EN disease and high LDH at lymphodepletion negatively impacted PFS (p=0.021 and <0.001, respectively), while sex, type of product administered, age and performance status did not predict PFS and OS. Of note, all the patients with involvement of gastrointestinal tract (n= 9), urinary tract (n= 9), or pharynx (n= 3) at lymphodepletion progressed or had an early relapse.In conclusions, both short and long term outcomes were similar in patients with EN and patients with ND at lymphodepletion, however patients with speci c sites of EN disease may demonstrate grim prognosis.

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