Phase I Alexander study of AUTO3, the first CD19/22 dual targeting CAR T cell therapy, with pembrolizumab in patients with relapsed/refractory (r/r) DLBCL.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8001-8001 ◽  
Author(s):  
Wendy Osborne ◽  
Maria Marzolini ◽  
Eleni Tholouli ◽  
Aravind Ramakrishnan ◽  
Carlos R. Bachier ◽  
...  
Keyword(s):  
T Cells ◽  
Median Number ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell Therapy ◽  
Car T ◽  
Secondary Endpoints ◽  
Adequate Organ Function ◽  
Dose Levels

8001 Background: CD19 directed CAR T cells are effective in patients with r/r DLBCL, however relapses due to CD19 loss or PDL1 upregulation are common. In this study, we evaluate the safety and efficacy of AUTO3, a CAR T targeting CD19/22 with limited duration of PD-1 blockade. Methods: We constructed a bicistronic retroviral vector encoding both an anti-CD19 (OX40 co-stim) and an anti-CD22 (41BB co-stim) CAR with humanized binders. The cell product was manufactured in a semi-automated and closed process using CliniMACS Prodigy. Patients (≥ 18 years) with r/r DLBCL (NOS) or transformed (tDLBCL); ECOG <2, adequate organ function are eligible. Lymphodepletion was Flu/Cy prior to AUTO3. Bridging therapy was allowed. The three dose levels explored are 50, 150, and 450 x 10^6 CAR T cells. Patients received AUTO3 alone, or with 3 doses of pembrolizumab (pem) 200 mg q 3 wks starting on D14 (regimen A), or with a single dose of pem 200 mg on D-1 (regimen B). The primary endpoint is frequency of DLTs and grade (G) 3-5 adverse events (AE) and secondary endpoints included ORR, CRR, and biomarkers. Results: As of Jan 21, 2020, 28 patients underwent leukapheresis, 27 successfully manufactured, 1 being manufactured, and 19 patients treated with AUTO3. The median age was 57 (28 - 71) and median number of prior therapies was 3 (2 - 10). 89% had refractory disease, 74% were DLBCL NOS, and 26% were tDLBCL. Dose escalation from 50 to 450 x 106 cells with pem regimen A and B have been completed without DLTs. G > 3 treatment emergent AEs that occurred > 15% were neutropenia (89%), thrombocytopenia (58%), anemia (47%), febrile neutropenia (16%), and hypophosphataemia (16%). Across all dose levels, there were 0% sCRS with primary infusion and 5% severe neurotoxicity (sNT) (1/19), which resolved. There were no cases of sCRS and no neurotoxicity of any grade at > 50 x 106 cells. Eighteen patients were evaluable for efficacy. Among the 11 treated at dose > 50 x 106, the ORR and CRR were 64% and 55%, and all CRs are ongoing (1-12 mth). Two out of 3 patients achieved CR at 450 x 106 cells on pem regimen B. Additional patients and longer follow up, as well as biomarkers, will be presented. Conclusions: AUTO3 at > 50 x 106 CAR T cells with pembrolizumab induces CRs without severe CRS or neurotoxicities of any grade. Clinical trial information: NCT03287817 .

scholarly journals Feasibility, and Efficacy of Donor-Derived cd19-Targeted Car t-Cell Therapy in Refractory/Relapsed(r/r)b-Cell Acute Lymphoblastic Leukemia (b-all) Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-6
Author(s):  
Xian Zhang ◽  
Junfang Yang ◽  
Wenqian Li ◽  
Gailing Zhang ◽  
Yunchao Su ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3

Backgrounds As CAR T-cell therapy is a highly personalized therapy, process of generating autologous CAR-T cells for each patient is complex and can still be problematic, particularly for heavily pre-treated patients and patients with significant leukemia burden. Here, we analyzed the feasibility and efficacy in 37 patients with refractory/relapsed (R/R) B-ALL who received CAR T-cells derived from related donors. Patients and Methods From April 2017 to May 2020, 37 R/R B-ALL patients with a median age of 19 years (3-61 years), were treated with second-generation CD19 CAR-T cells derived from donors. The data was aggregated from three clinical trials (www.clinicaltrials.gov NCT03173417; NCT02546739; and www.chictr.org.cn ChiCTR-ONC-17012829). Of the 37 patients, 28 were relapsed following allogenic hematopoietic stem cell transplant (allo-HSCT) and whose lymphocytes were collected from their transplant donors (3 HLA matched sibling and 25 haploidentical). For the remaining 9 patients without prior transplant, the lymphocytes were collected from HLA identical sibling donors (n=5) or haploidentical donors (n=4) because CAR-T cells manufacture from patient samples either failed (n=5) or blasts in peripheral blood were too high (&gt;40%) to collect quality T-cells. The median CAR-T cell dose infused was 3×105/kg (1-30×105/kg). Results For the 28 patients who relapsed after prior allo-HSCT, 27 (96.4%) achieved CR within 30 days post CAR T-cell infusion, of which 25 (89.3%) were minimal residual disease (MRD) negative. Within one month following CAR T-cell therapy, graft-versus-host disease (GVHD) occurred in 3 patients including 1 with rash and 2 with diarrhea. A total of 19 of the 28 (67.9%) patients had cytokine release syndrome (CRS), including two patients (7.1%) with Grade 3-4 CRS. Four patients had CAR T-cell related neurotoxicity including 3 with Grade 3-4 events. With a medium follow up of 103 days (1-669days), the median overall survival (OS) was 169 days (1-668 days), and the median leukemia-free survival (LFS) was 158 days (1-438 days). After CAR T-cell therapy, 15 patients bridged into a second allo-HSCT and one of 15 patients (6.7%) relapsed following transplant, and two died from infection. There were 11 patients that did not receive a second transplantation, of which three patients (27.3%) relapsed, and four parents died (one due to relapse, one from arrhythmia and two from GVHD/infection). Two patients were lost to follow-up. The remaining nine patients had no prior transplantation. At the time of T-cell collection, the median bone marrow blasts were 90% (range: 18.5%-98.5%), and the median peripheral blood blasts were 10% (range: 0-70%). CR rate within 30 days post CAR-T was 44.4% (4/9 cases). Six patients developed CRS, including four with Grade 3 CRS. Only one patient had Grade 3 neurotoxicity. No GVHD occurred following CAR T-cell therapy. Among the nine patients, five were treated with CAR T-cells derived from HLA-identical sibling donors and three of those five patients achieved CR. One patient who achieved a CR died from disseminated intravascular coagulation (DIC) on day 16. Two patients who achieved a CR bridged into allo-HSCT, including one patient who relapsed and died. One of two patients who did not response to CAR T-cell therapy died from leukemia. Four of the nine patients were treated with CAR T-cells derived from haploidentical related donors. One of the four cases achieved a CR but died from infection on day 90. The other three patients who had no response to CAR T-cell therapy died from disease progression within 3 months (7-90 days). Altogether, seven of the nine patients died with a median time of 19 days (7-505 days). Conclusions We find that manufacturing CD19+ CAR-T cells derived from donors is feasible. For patients who relapse following allo-HSCT, the transplant donor derived CAR-T cells are safe and effective with a CR rate as high as 96.4%. If a patient did not have GVHD prior to CAR T-cell therapy, the incidence of GVHD following CAR T-cell was low. Among patients without a history of transplantation, an inability to collect autologous lymphocytes signaled that the patient's condition had already reached a very advanced stage. However, CAR T-cells derived from HLA identical siblings can still be considered in our experience, no GVHD occurred in these patients. But the efficacy of CAR T-cells from haploidentical donors was very poor. Disclosures No relevant conflicts of interest to declare.

scholarly journals Allogeneic Hematopoietic Cell Transplantation Is Critical to Maintain Remissions after CD19-CAR T-Cell Therapy for Pediatric ALL: A Single Center Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 39-40
Author(s):  
Aimee C Talleur ◽  
Renee M. Madden ◽  
Amr Qudeimat ◽  
Ewelina Mamcarz ◽  
Akshay Sharma ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
T Cell Therapy ◽  
Allogeneic Hct ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

CD19-CAR T-cell therapy has shown remarkable efficacy in pediatric patients with relapsed and/or refractory B-cell acute lymphoblastic leukemia (r/r ALL). Despite high short-term remission rates, many responses are not durable and the best management of patients who achieve a complete response (CR) post-CAR T-cell therapy remains controversial. In particular, it is unclear if these patients should be observed or proceed to consolidative allogeneic hematopoietic cell transplantation (HCT). To address this question, we reviewed the clinical course of all patients (n=22) who received either an investigational CAR T-cell product (Phase I study: SJCAR19 [NCT03573700]; n=12) or tisagenlecleucel (n=10) at our institution. The investigational CD19-CAR T cells were generated by a standard cGMP-compliant procedure using a lentiviral vector encoding a 2nd generation CD19-CAR with a FMC63-based CD19 binding domain, CD8a stalk and transmembrane domain, and 41BB.ζ signaling domain. Patients received therapy between 8/2018 and 3/2020. All products met manufacturing release specifications. Within the entire cohort, median age at time of infusion was 12.3 years old (range: 1.8-23.5) and median pre-infusion marrow burden using flow-cytometry minimal residual disease (MRD) testing was 6.8% (range: 0.003-100%; 1 patient detectable by next-generation sequencing [NGS] only). All patients received lymphodepleting chemotherapy (fludarabine, 25mg/m2 daily x3, and cyclophosphamide, 900mg/m2 daily x1), followed by a single infusion of CAR T-cells. Phase I product dosing included 1x106 CAR+ T-cells/kg (n=6) or 3x106 CAR+ T-cells/kg (n=6). Therapy was well tolerated, with a low incidence of cytokine release syndrome (any grade: n=10; Grade 3-4: n=4) and neurotoxicity (any grade: n=8; Grade 3-4: n=3). At 4-weeks post-infusion, 15/22 (68.2%) patients achieved a CR in the marrow, of which 13 were MRDneg (MRDneg defined as no detectable leukemia by flow-cytometry, RT-PCR and/or NGS, when available). Among the 2 MRDpos patients, 1 (detectable by NGS only) relapsed 50 days after CAR T-cell infusion and 1 died secondary to invasive fungal infection 35 days after infusion. Within the MRDneg cohort, 6/13 patients proceeded to allogeneic HCT while in MRDneg/CR (time to HCT, range: 1.8-2.9 months post-CAR T-cell infusion). All 6 HCT recipients remain in remission with a median length of follow-up post-HCT of 238.5 days (range 19-441). In contrast, only 1 (14.3%) patient out of 7 MRDneg/CR patients who did not receive allogeneic HCT, remains in remission with a follow up of greater 1 year post-CAR T-cell infusion (HCT vs. no HCT: p&lt;0.01). The remaining 6 patients developed recurrent detectable leukemia within 2 to 9 months post-CAR T-cell infusion (1 patient detectable by NGS only). Notably, recurring leukemia remained CD19+ in 4 of 5 evaluable patients. All 4 patients with CD19+ relapse received a 2nd CAR T-cell infusion (one in combination with pembrolizumab) and 2 achieved MRDneg/CR. There were no significant differences in outcome between SJCAR19 study participants and patients who received tisagenlecleucel. With a median follow up of one year, the 12 month event free survival (EFS) of all 22 patients is 25% (median EFS: 3.5 months) and the 12 month overall survival (OS) 70% (median OS not yet reached). In conclusion, infusion of investigational and FDA-approved autologous CD19-CAR T cells induced high CR rates in pediatric patients with r/r ALL. However, our current experience shows that sustained remission without consolidative allogeneic HCT is not seen in most patients. Our single center experience highlights not only the need to explore maintenance therapies other than HCT for MRDneg/CR patients, but also the need to improve the in vivo persistence of currently available CD19-CAR T-cell products. Disclosures Sharma: Spotlight Therapeutics: Consultancy; Magenta Therapeutics: Other: Research Collaboration; CRISPR Therapeutics, Vertex Pharmaceuticals, Novartis: Other: Clinical Trial PI. Velasquez:St. Jude: Patents & Royalties; Rally! Foundation: Membership on an entity's Board of Directors or advisory committees. Gottschalk:Patents and patent applications in the fields of T-cell & Gene therapy for cancer: Patents & Royalties; TESSA Therapeutics: Other: research collaboration; Inmatics and Tidal: Membership on an entity's Board of Directors or advisory committees; Merck and ViraCyte: Consultancy.

Update of CARTITUDE-1: A phase Ib/II study of JNJ-4528, a B-cell maturation antigen (BCMA)-directed CAR-T-cell therapy, in relapsed/refractory multiple myeloma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8505-8505 ◽  
Author(s):  
Jesus G. Berdeja ◽  
Deepu Madduri ◽  
Saad Zafar Usmani ◽  
Indrajeet Singh ◽  
Enrique Zudaire ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Phase 1B

8505 Background: JNJ-68284528 (JNJ-4528) is a chimeric antigen receptor T (CAR-T) cell therapy containing 2 BCMA-targeting single-domain antibodies. Here we present updated CARTITUDE-1 (NCT03548207) phase 1b results with longer follow-up. Methods: Pts had MM per IMWG criteria, measurable disease, received ≥3 prior regimens or were double refractory to a PI and IMiD, and received anti-CD38 antibody. Cyclophosphamide 300 mg/m2+ fludarabine 30 mg/m2 over 3 days were used for lymphodepletion. JNJ-4528 (median, 0.73x106 CAR+ viable T cells/kg) was given as a single infusion. Cytokine release syndrome (CRS) was graded by Lee et al2014 and neurotoxicity by CTCAE, v5.0 and ASTCT grading. Response was assessed per IMWG criteria. Results: As of 17 Jan 2020, median follow-up is 9 mo (3–17). Phase 1b enrollment is complete (N = 29 treated; median 5 (3–18) prior lines, 76% penta-exposed, 86% triple-refractory, 31% penta-refractory, 97% refractory to last line of therapy). Most frequent adverse events (AEs) were neutropenia (100%), CRS (93%), and thrombocytopenia (93%). Grade (Gr) ≥3 hematologic AEs were neutropenia (100%), thrombocytopenia (69%), and leukopenia (59%). 27 (93%) pts had CRS; 25 Gr 1–2, 1 Gr 3, and 1 Gr 5 (day 99 subsequent to dose-limiting toxicity of prolonged Gr 4 CRS). Median time to onset of CRS was 7 days (2–12). 4 pts had treatment-related neurotoxicity: 3 Gr 1–2 and 1 Gr 3. ORR was 100%, with 22 (76%) stringent complete responses (sCRs), 6 (21%) very good partial responses (VGPRs), and 1 (3%) PR. Median time to ≥CR was 2 mo (1–9). 26/29 pts are progression-free, with 6-mo progression-free survival rate of 93% and longest response ongoing at 15 mo. 1 death due to CRS and 1 to acute myeloid leukemia (not treatment-related) occurred during the study. All 16 pts (14 sCR, 2 VGPR) evaluable at 6 mo were minimal residual disease negative at 10−5 or 10−6. JNJ-4528 CAR+ T cell expansion peaked between day 10–14. At 6-mo individual follow-up, 22/28 pts had JNJ-4528 CAR+ T cells below the level of quantification (2 cells/µL) in peripheral blood, suggesting CAR-T persistence in peripheral blood did not seem to correlate with deepening of response. At peak expansion, preferential expansion of CD8+ CAR-T cells with a central memory phenotype was observed in peripheral blood. Conclusions: JNJ-4528 treatment led to responses in all pts. These responses were early, deep, and durable at a low dose of CAR-T cells with 26/29 (90%) pts progression free at median 9-mo follow-up. CRS was manageable in most pts, supporting outpatient dosing. Clinical trial information: NCT03548207 .

Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL

2021 ◽  
pp. JCO.20.02262
Author(s):  
Nirali N. Shah ◽  
Daniel W. Lee ◽  
Bonnie Yates ◽  
Constance M. Yuan ◽  
Haneen Shalabi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

PURPOSE CD19 chimeric antigen receptor (CD19-CAR) T cells induce high response rates in children and young adults (CAYAs) with B-cell acute lymphoblastic leukemia (B-ALL), but relapse rates are high. The role for allogeneic hematopoietic stem-cell transplant (alloHSCT) following CD19-CAR T-cell therapy to improve long-term outcomes in CAYAs has not been examined. METHODS We conducted a phase I trial of autologous CD19.28ζ-CAR T cells in CAYAs with relapsed or refractory B-ALL. Response and long-term clinical outcomes were assessed in relation to disease and treatment variables. RESULTS Fifty CAYAs with B-ALL were treated (median age, 13.5 years; range, 4.3-30.4). Thirty-one (62.0%) patients achieved a complete remission (CR), 28 (90.3%) of whom were minimal residual disease−negative by flow cytometry. Utilization of fludarabine/cyclophosphamide–based lymphodepletion was associated with improved CR rates (29/42, 69%) compared with non–fludarabine/cyclophosphamide–based lymphodepletion (2/8, 25%; P = .041). With median follow-up of 4.8 years, median overall survival was 10.5 months (95% CI, 6.3 to 29.2 months). Twenty-one of 28 (75.0%) patients achieving a minimal residual disease−negative CR proceeded to alloHSCT. For those proceeding to alloHSCT, median overall survival was 70.2 months (95% CI, 10.4 months to not estimable). The cumulative incidence of relapse after alloHSCT was 9.5% (95% CI, 1.5 to 26.8) at 24 months; 5-year EFS following alloHSCT was 61.9% (95% CI, 38.1 to 78.8). CONCLUSION We provide the longest follow-up in CAYAs with B-ALL after CD19-CAR T-cell therapy reported to date and demonstrate that sequential therapy with CD19.28ζ-CAR T cells followed by alloHSCT can mediate durable disease control in a sizable fraction of CAYAs with relapsed or refractory B-ALL (ClinicalTrials.gov identifier: NCT01593696 ).

Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in relapsed and refractory multiple myeloma: Updated KarMMa results.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8016-8016
Author(s):  
Larry D. Anderson, Jr ◽  
Nikhil C. Munshi ◽  
Nina Shah ◽  
Sundar Jagannath ◽  
Jesus G. Berdeja ◽  
...  
Keyword(s):  
T Cells ◽  
Dose Range ◽  
Target Dose ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell Therapy ◽  
Car T ◽  
Heavily Pretreated ◽  
Grade 3

8016 Background: Patients (pts) with RRMM previously exposed to immunomodulatory agents, proteasome inhibitors (PIs), and CD38 antibodies (mAbs) have poor outcomes with subsequent treatments. Ide-cel, a BCMA-directed CAR T cell therapy, showed frequent, deep, and durable responses in heavily pretreated pts with RRMM in the pivotal KarMMa trial (Munshi NC, et al. J Clin Oncol 2020;38[suppl 15]. Abstract 8503). Here, we present updated data. Methods: Pts with ≥ 3 prior regimens (including immunomodulatory agent, PI, and CD38 mAb) and refractory to their last regimen per IMWG criteria were eligible (NCT03361748). Pts received 150─450 × 106 CAR+ T cells (target dose range) after 3 days of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2). Endpoints included overall response rate (ORR; primary) and complete response (CR) rate (key secondary). Additional secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: KarMMa enrolled 140 pts, and 128 received ide-cel. Pts had a median age of 61 years and a median of 6 (range, 3-16) prior regimens; 84% were triple-class refractory, and 26% were penta-class refractory (lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab). Most pts (88%) had bridging therapy. Median follow-up was 15.4 mo (data cutoff, 7 Apr 2020). ORR was 73% and median PFS was 8.8 mo in all treated pts; both increased with higher dose (Table). At the highest target dose (450 × 106 CAR+ T cells), the ORR was 81%, the CR rate was 39%, and the median PFS increased to 12.2 months with longer follow-up. Responses were observed in all subgroups including difficult-to-treat subsets (eg, extramedullary disease [ORR, 70%], high tumor burden [71%], and R-ISS stage III disease [48%]). OS continues to mature and the median has not been reached; the 15-month event-free rate for OS was 71%. Cytopenias (97%) and cytokine release syndrome (CRS; 84%) were the most common any-grade toxicities. CRS was mostly grade 1/2; 5 pts (4%) had grade 3, 1 had grade 4 (at 300 × 106), and 1 had grade 5 (at 300 × 106). Investigator-identified neurotoxicity was reported in 23 pts (18%); 4 pts (3%) had grade 3 and 0 had grade ≥ 4. Tocilizumab was used in 67 and 3 pts with CRS and neurotoxicity, respectively. Conclusions: Updated results from the KarMMa trial continue to demonstrate deep, durable responses with ide-cel in heavily pretreated pts with RRMM. Efficacy and safety reflect prior reports and support a favorable clinical benefit-risk profile for ide-cel across the target dose range. Clinical trial information: NCT03361748. [Table: see text]

scholarly journals KarMMa-3: A Phase 3 Study of Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T Cell Therapy Vs Standard Regimens in Relapsed and Refractory Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 24-25
Author(s):  
Michel Delforge ◽  
Rachid C. Baz ◽  
Michele Cavo ◽  
Natalie S. Callander ◽  
Armin Ghobadi ◽  
...  
Keyword(s):  
T Cells ◽  
Board Of Directors ◽  
Research Funding ◽  
Advisory Committees ◽  
T Cell Therapy ◽  
For Profit ◽  
Car T Cells ◽  
Car T Cell Therapy ◽  
Car T ◽  
Secondary Endpoints

BACKGROUND: Patients with relapsed and refractory multiple myeloma (RRMM) who progress on immunomodulatory agents, proteasome inhibitors (PIs), and anti-CD38 antibodies have poor outcomes, highlighting the need for novel targets for the disease. The BCMA-directed CAR T cell therapy ide-cel previously demonstrated deep, durable responses in heavily pretreated patients with RRMM (Raje N, et al. N Engl J Med. 2019;380:1726-1737; Munshi NC, et al. J Clin Oncol. 2020;38[suppl] [abstract 8503]). In the pivotal phase 2 KarMMa study, overall response rate (ORR), complete response rate, and median duration of response (DOR) were 73%, 33%, and 10.7 months, respectively, across the target dose levels of 150−450 × 106 CAR+ T cells, and 82%, 39%, and 11.3 months at the highest target dose of 450 × 106 CAR+ T cells. In order to examine the effect of ide-cel as an earlier line of treatment, the multicenter, randomized, open-label, phase 3 study, KarMMa-3, was opened to compare ide-cel vs standard regimens in patients whose disease is refractory to the last line of therapy. STUDY DESIGN: Patients with RRMM who had received 2-4 prior regimens (including ≥ 2 consecutive cycles of daratumumab [DARA], an immunomodulatory agent, and a PI [individually or in combinations]) are randomized 2:1 to receive ide-cel or one of the following standard regimens based on the patient's most recent regimen and investigator discretion: DARA + pomalidomide (POM) + dexamethasone (DEX; DPd), DARA + bortezomib + DEX (DVd), ixazomib + lenalidomide + DEX (IRd), carfilzomib + DEX (Kd), or elotuzumab + POM + DEX (EPd). Patients in the standard-regimen arm of this study are eligible to receive ide-cel after confirmed evidence of progressive disease. Randomization is stratified by age (&lt; 65 vs ≥ 65 years), number of prior regimens (2 vs 3 or 4), and high-risk cytogenetics (t(4;14), t(14;16), or del(17p); yes vs no). Patients must be ≥ 18 years of age, have Eastern Cooperative Oncology Group performance status of 0-1, have disease that is refractory to the last treatment regimen, and have achieved minimal or better response to ≥ 1 prior regimen. Patients with nonsecretory myeloma, central nervous system involvement, prior allogeneic stem cell transplant, prior BCMA-targeted therapy, or prior gene or cellular therapy for cancer are excluded. Ide-cel is manufactured following leukapheresis and then infused (at dose levels from 150 to 450 × 106, but targeting 450 × 106, CAR+ T cells) after 2 days of rest following lymphodepletion with 3 days of fludarabine 30 mg/m2 + cyclophosphamide 300 mg/m2. Up to 1 cycle of DPd, DVd, IRd, Kd, or EPd may be given as bridging therapy while ide-cel is being manufactured. The primary endpoint is progression-free survival. The key secondary endpoints are ORR and overall survival. Other secondary endpoints include minimal residual disease, DOR, safety, pharmacokinetics, and quality of life. Immunogenicity and biomarkers are exploratory endpoints. KarMMa-3 is registered at ClinicalTrials.gov: NCT03651128. Disclosures Delforge: Amgen, Celgene, Janssen, Takeda: Honoraria. Baz:Sanofi, Karypharm, Janssen, Celgene: Other: Advisory board; Karyopharm, janssen, Bristol Myers Squibb, Celgene, Merck, Sanofi, Abbvie Inc.: Research Funding. Cavo:BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Honoraria, Speakers Bureau; Karyopharm: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Callander:University of Wisconsin: Current Employment; Cellectar: Research Funding. Ghobadi:Atara: Consultancy; Celegene: Consultancy; EUSA: Consultancy; Wugen: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau. Rodriguez-Otero:GlaxoSmithKline: Consultancy, Current Employment, Current equity holder in publicly-traded company, Honoraria; Kite: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Sanofi: Consultancy, Honoraria; Medscape: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Mateos:Adaptive Biotechnologies: Honoraria; GlaxoSmithKline: Honoraria; Abbvie: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; EDO Mundipharma: Honoraria; Seattle Genetics: Honoraria; Roche: Honoraria. Massaro:bluebird bio: Current Employment, Current equity holder in publicly-traded company. Ding:Bristol-Myers Squibb Company: Current Employment. Patel:BMS: Current Employment. Pittari:Bristol-Myers Squibb Company: Current Employment. Novick:Bristol-Myers Squibb Company: Current Employment. Giralt:OMEROS: Consultancy, Honoraria; NOVARTIS: Consultancy, Honoraria, Research Funding; KITE: Consultancy; MILTENYI: Consultancy, Research Funding; ACTINUUM: Consultancy, Research Funding; TAKEDA: Research Funding; AMGEN: Consultancy, Research Funding; JAZZ: Consultancy, Honoraria; CELGENE: Consultancy, Honoraria, Research Funding. Berdeja:Bioclinica: Consultancy; CURIS: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; Constellation: Research Funding; Abbvie: Research Funding; Glenmark: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Vivolux: Research Funding; EMD Sorono: Research Funding; Kesios: Research Funding; Kite Pharma: Consultancy; Legend: Consultancy; Lilly: Research Funding; Novartis: Research Funding; Poseida: Research Funding; Prothena: Consultancy; Teva: Research Funding; Bluebird: Research Funding; BMS: Consultancy, Research Funding; Cellularity: Research Funding; Genentech, Inc.: Research Funding; Servier: Consultancy; Amgen: Consultancy, Research Funding; Acetylon: Research Funding; Takeda: Consultancy, Research Funding; Karyopharm: Consultancy.

scholarly journals Updated Phase 1 Results of a First-in-Human Open-Label Study of Lcar-B38M, a Structurally Differentiated Chimeric Antigen Receptor T (CAR-T) Cell Therapy Targeting B-Cell Maturation Antigen (Bcma)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1858-1858 ◽  
Author(s):  
Lijuan Chen ◽  
Jie Xu ◽  
Weijun Fu ◽  
Shiwei Jin ◽  
Shuangshuang Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Adverse Events ◽  
Cell Therapy ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3

Background: LCAR-B38M is a structurally differentiated CAR-T cell therapy containing 2 BCMA-targeting single-domain antibodies designed to confer avidity. LEGEND-2 (NCT03090659) is an exploratory study using LCAR-B38M CAR-T cells for the treatment of patients (pts) with relapsed or refractory (R/R) multiple myeloma (MM). Key eligibility criteria included R/R MM ³3 prior lines of therapy. Earlier results from LEGEND-2 showed encouraging overall efficacy and manageable safety (N=74). Here, we present updated results of LCAR-B38M in 17 R/R MM pts published in PNAS (Xu J et al. Proc Natl Acad Sci USA. 2019;116:9543-9551), with a median follow-up of 22 months, from 3 sites: Jiangsu Provincial People's Hospital, Nanjing (JS); Ruijin Hospital, Shanghai (RJ); and Changzheng Hospital, Shanghai (CZ). Methods: Different sites adopted different lymphodepletion and dosing regimens. Eight pts (age, 18-75 years) with R/R MM received a lymphodepletion regimen of cyclophosphamide (Cy) 250 mg/m2 + fludarabine (Flu) 25 mg/m2, intravenously daily for 3 days (RJ and CZ), while 9 pts received Cy 300 mg/m2 intravenously daily for 3 days (JS). CAR-T cells were administered via 3 infusions (day 0, 3, and 6; n=8, RJ and CZ) or 1 infusion (day 0; n=9, JS) 5 days after lymphodepletion. Response was assessed per the International Myeloma Working Group criteria, adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, and cytokine release syndrome was graded using CARTOX criteria (Neelapu SS et al. Nat Rev Clin Oncol. 2018;15:47-62). Results: Overall, 17 pts were enrolled. The mean dose was 0.7x106 (range, 0.2-1.5x106) CAR+ T cells/kg. The most common adverse events observed were cytokine release syndrome (100%; grade 1/2 [n=10]; grade 3 [n=6]; grade 5 [n=1]); cytopenia (82%; grade 1/2 [n=4]; grade 3 [n=5]; grade 4 [n=5]); and liver toxicity: 100%; elevated alanine aminotransferase (41%; grade 1/2 [n=7]; grade ≥3 [n=0]), elevated aspartate aminotransferase (94%, grade 1/2 [n=11]; grade 3 [n=5]), and elevated bilirubin (6%, grade 3 [n=1]). Tumor lysis syndrome was reported in 3 pts (18%) and no neurotoxicity was reported. The overall best response rate (partial response or better) was 88% (95% confidence interval [CI], 64-99). Complete response (CR) was achieved by 14 pts (82%; 62-99), and very good partial response by 1 pt (6%; 6-18). All of the 14 pts with CR were minimal residual disease negative (MRD-neg, by 8-color flow cytometry). The median time to first response was 1.0 months. At the July 20, 2019 data cutoff (median follow-up, 22 months [95% confidence interval, 16-23]), 6 (38%) pts remain progression-free. The median progression-free survival (PFS) for all-treated pts was 12 months (12-NE); median PFS for MRD-neg pts with CR was 18 months (13-NE). The median overall survival has not yet been reached (NE [12-NE]). At 18 months, 65% (39-90) of all-treated pts and 79% (54-99) of MRD-neg pts with CR were still living. In a post-hoc analysis, PFS was longer in pts at the RJ and CZ sites than in those at the JS site. Relapse occurred in 8/9 pts at the JS site, while relapse or progressive disease occurred in 2/7 evaluable pts at the RJ and CZ sites. In addition, 5/7 (71%) RJ/CZ pts remained stable in sCR (median follow-up, 745 days). Key differences between these sites included lymphodepletion regimens and the number of CAR-T infusions. Conclusions: LCAR-B38M has a safety profile consistent with other BCMA-targeted CAR-T cell therapy. This exploratory study has provided key evidence that LCAR-B38M may be a highly effective therapy for pts with R/R MM. It demonstrated deep and durable responses, particularly following Cy/Flu lymphodepletion. Although the sample size is too small to draw firm conclusions and multiple other factors may contribute, these outcomes suggest that different lymphodepletion regimens may contribute to differences in long-term efficacy. The study is ongoing for long-term safety and follow-up. A phase 1b/2 clinical study is ongoing in the United States (CARTITUDE-1, NCT03548207, JNJ-4528), and a phase 2 confirmatory study is ongoing in China (CARTIFAN-1, NCT03758417, LCAR-B38M). Pts in both of these studies will undergo Cy/Flu lymphodepletion and 1 single infusion of drug product. Disclosures Xu: National Natural Science Foundation of China: Other: Grants; Shanghai Rising-Star Program: Other: Grants; Shanghai Excellent Youth Medical Talents Training Program: Other: Grants.

scholarly journals Phase I Study of AUTO3, a Bicistronic Chimeric Antigen Receptor (CAR) T-Cell Therapy Targeting CD19 and CD22, in Pediatric Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (r/r B-ALL): Amelia Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2620-2620 ◽  
Author(s):  
Persis J Amrolia ◽  
Robert Wynn ◽  
Rachael E Hough ◽  
Ajay Vora ◽  
Denise Bonney ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Employment Equity ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Equity Ownership

Introduction CAR T-cell therapies directed against CD19 or CD22 have shown remarkable activity in r/r B-ALL but relapse due to target antigen down-regulation/loss has been the major cause of treatment failure. To address this, we developed AUTO3, a CAR T-cell therapy designed to target CD19 and CD22 simultaneously. Preliminary results of this study showed an acceptable safety profile and encouraging efficacy in pediatric r/r B-ALL (all 6 patients treated in active doses ≥3 x 106 CAR T-cells/ Kg achieved complete remission (CR) with negative minimal residual disease (MRD) (Amrolia et al, Blood 2018 132:279). Here we present the updated results of CAR naïve patients treated at the active doses. Methods & Patients We constructed a bicistronic retroviral vector encoding both an anti-CD19 CAR and an anti-CD22 CAR. This second-generation CAR incorporated an OX40 co-stimulatory domain for the CD19 CAR and a 41BB for the CD22 CAR. The cell product was manufactured on a semi-automated/closed process. Patients (aged 1‒24 years) with high risk relapsed (IBFM criteria) or refractory B-ALL, adequate performance score/organ function, an absolute lymphocyte count ≥0.5 x 109/L are eligible. Patients with CNS Grade 3 disease, active graft versus host disease are excluded. Patients receive lymphodepletion with 30 mg/m2/day fludarabine x 4 days and 500 mg/m2/day cyclophosphamide x 2 days prior to AUTO3 infusion. Three dose levels were explored (1 x 106, 3 x 106, and 5 x 106 cells/kg), CAR T cells are infused as a single (for <25% blasts) or split (for ≥25% blasts) dose based on leukemia burden. Bridging therapy is allowed during the manufacturing period. The primary endpoint is the frequency of dose-limiting toxicities (DLTs) and key secondary endpoints include morphological/MRD negative CR rate, disease-free survival, overall survival, as well as AUTO3 levels and persistence in blood and bone marrow. Results As of the data cut-off date (June 17, 2019), 10 patients received AUTO3 at 3 x 106 cells/Kg (n= 5, of whom 1 received split dose) or 5 x 106 CAR T-cells/Kg (n= 5, all of them received single infusion). The median transduction efficiency was 15.5% (range 8.6‒39.3%). Median age was 8.5 years (range 5‒16 years) and 5 (50%) patients had prior haemopoietic stem cell transplant (HSCT). One patient (10%) had prior anti-CD19 CAR-T cells. The disease burden at Day ‒7 ranged from 0 to 38% (median 7.5%) blasts. Among the 10 treated patients, 2 have not completed the 30 days post-infusion DLT observation period as of the cut-off date. No deaths or DLTs were observed. MTD has not yet been reached. The most common grade (Gr) ≥3 adverse events were neutropenia (60%), anaemia (50%), pyrexia (40%), febrile neutropenia (40%) and thrombocytopenia (30%). Eight patients (80%) had Gr 1 cytokine release syndrome (CRS), one (10%) had Gr 2 CRS; no ≥Gr 3 CRS was observed. Only one patient was treated with tocilizumab and none required admission to ICU due to CRS. One patient (10%) experienced Gr 1 neurotoxicity; no ≥ Gr 2 neurotoxicity was reported. Among the 9 CAR naïve patients, 7 (4 in the 3 x 106 cells/Kg dose cohort, 3 in the 5 x 106 cells/Kg dose cohort) had a minimum of 8 weeks' follow up and were evaluable for efficacy analysis. All 7 patients achieved CR/CRi (100%) following AUTO3 infusion as well as molecular negative remission (100%). After a median follow-up of 8 months (range 2-12), emergence of MRD by PCR occurred in four patients, lack of persistence of circulating CAR T-cells was observed in 3 of the 4 patients. Three relapses were reported including one with CD19 negative/CD22 low expression at 1 year after treatment. One patient in ongoing molecular remission proceeded to HSCT. All the remaining 4 patients in ongoing CR/CRi maintain B-cell aplasia. The median CAR T-cell expansion (expressed as vector copy number per microgram of DNA) at peak was 102K (range 56-128). The median persistence of CAR-T cells in blood was 180 days (range 21-330). Updated data with longer follow up and additional patient data will be presented. Conclusion This interim data analysis demonstrates that AUTO3 at ≥3 x 106 cells dose achieved 100% molecular remission rate with a favourable safety profile, no ≥ Gr 3 CRS or ≥ Gr 2 neurotoxicity was reported. The most common cause of relapse was antigen positive relapse due to lack of CAR T cell persistence. Evaluation of patients with a modified manufacturing process is planned. Disclosures Amrolia: UCLB: Patents & Royalties. Clark:Autolus Ltd: Employment, Equity Ownership. Al-Hajj:Autolus Therapeutics: Employment, Equity Ownership. Cordoba:Autolus: Employment, Equity Ownership. Kotsopoulou:Autolus Therapeutics: Employment, Equity Ownership. Khokhar:Autolus Therapeutics: Employment, Equity Ownership. Pule:Autolus: Employment, Equity Ownership, Patents & Royalties. Peddareddigari:Autolus Therapeutics: Employment, Equity Ownership.

CD19-Targeted 19-28z CAR Modified Autologous T Cells Induce High Rates of Complete Remission and Durable Responses in Adult Patients with Relapsed, Refractory B-Cell ALL

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 382-382 ◽  
Author(s):  
Jae H Park ◽  
Isabelle Riviere ◽  
Xiuyan Wang ◽  
Yvette J Bernal ◽  
Sarah Yoo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Adult Patients ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract Background: Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and dismal prognosis with a median overall survival (OS) < 6 months and 5-year OS ≤10%. We have previously reported a high anti-tumor activity of autologous T cells genetically modified to express 19-28z chimeric antigen receptor (19-28z CAR) targeting CD19 in adult patients with CLL and ALL (Brentjens R et al. Blood 2011; Davila M et al. Sci Transl Med2014). Herein, for the first time, we further report the long-term outcome of our phase I clinical trial in adults with relapsed/refractory (R/R) ALL (NCT01044069) with analysis on potential predictive markers of response and neurological toxicities. Patients and Methods: Adult patients with R/R B-ALL were enrolled. Eligible patients underwent leukapheresis, and T cells were transduced with a retrovirus encoding a CAR construct composed of anti-CD19 scFV linked to CD28 and CD3ζ signaling domains (19-28z). All patients received lymphodepleting chemotherapy followed 2 days later by 1x106 – 3x10619-28z CAR T cells/kg. The primary objective of the study was to evaluate the safety and anti-tumor activity of 19-28z CAR T cells in ALL. Post-treatment minimal residual disease (MRD) was assessed at day 14-28 by multiparameter flow cytometry and deep sequencing in the bone marrow (BM) samples (Adaptive Biotech Corp.) Results: 24 patients have been treated. The median age was 56 years (range, 23-74). 6 patients (25%) had Ph+ B-ALL (T315I mutation in 2 patients), 6 patients (25%) had prior allogeneic hematopoietic stem cell transplant (allo-HSCT), and 11 patients (46%) had 3 or more prior lines of ALL therapy before receiving the 19-28z CAR T cell therapy. Of the 24 patients, 22 patients were evaluable for response. At the time of 19-28z CAR T cell infusion, 12 of 22 patients had morphologic disease (6 to 97% blasts in the BM) and the remaining 10 patients had MRD. Twenty out of 22 patients (91%) were in complete remission (CR) after 19-28z CAR T-cell infusion, and 18 of these 20 patients (90%) achieved an MRD-negative CR. Ten of the 13 transplant eligible patients (77%) successfully underwent allo-HSCT following the 19-28z CAR T cell therapy. As of July 1, 2014, the median follow-up was 7.4 months (range 1-34), with 13 patients having at least 6 months of follow-up. Responses appear durable with 6 patients remaining disease-free beyond 1 year (range 12.6 – 34 months). Median overall survial (OS) is 9 months. 5 patients relapsed during the follow-up, including 1 patient with CD19 negative relapse. Three of the relapsed patients were treated again with the 19-28z CAR T cells, and two patients achieved a second CR. Comparing responders to non-responders, no association was observed between response and age (<60 vs. ≥60), prior allo-HSCT, number of prior therapies, or pre-treatment blast percentage. While none of the 10 patients with MRD at the time of T cell infusion developed cytokine release syndrome (CRS), 9 of 13 patients with morphologic disease at the time of the T cell infusion developed CRS with or without neurological symptoms that required intervention with an IL-6R antagonist or corticosteroid. A detailed analysis of serum cytokines demonstrated a consistent peak of IL-6 (22.2 to 553-fold increase) immediately prior to the development of neurological toxicities. Based on these data, we have developed a multi-disciplinary CRS management algorithm for patients at high risk in order to reduce the severity of CRS and improve safety of the 19-28z CAR T cell therapy. Conclusions: While longer follow-up is needed to confirm the durability of the observed responses, the potent induction of MRD-negative responses and successful long-term outcomes, including subsequent allo-HSCT without apparent additional post-transplant toxicities, strongly support the use of 19-28z CAR T cells in adult patients with B-ALL. A temporal relationship between serum IL-6 levels and neurological toxicities indicates that early intervention with IL-6 directed therapy may be more effective in ameliorating neurological toxicities in patients with morphologic disease at the time of T-cell infusion. These findings will need to be evaluated systematically and confirmed in a larger phase 2 trial. Disclosures Park: Juno Therapeutics: Research Funding. Riviere:Juno Therapeutics: Consultancy, scientific co-founders Other. Sadelain:Juno Therapeutics: Consultancy, Scientific co-founder and Stock holder Other. Brentjens:Juno Therapeutics: Consultancy, Scientific co-founder and Stock holder Other.

scholarly journals Feasibility of Outpatient CAR T Cell Therapy: Experience of a Single Institution

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4828-4828
Author(s):  
Yusra F Shao ◽  
Dipenkumar Modi ◽  
Andrew Kin ◽  
Asif Alavi ◽  
Lois Ayash ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3

Abstract Background Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a promising therapeutic option for relapsed/refractory non-Hodgkin lymphoma. However, access to CAR T cell therapy remains limited as CAR T cells are routinely administered in the hospital setting. Hence, there's a growing interest in standardizing outpatient administration of CAR T cells to increase patient access and minimize costs. Here, we describe our institution's experience with outpatient administration of CAR T cells. Methods In this retrospective study, we reviewed who received CAR T cell therapy in the outpatient setting at Karmanos Cancer Center between June 2019 and June 2021.Charts were reviewed for age, disease pathology, prior lines of therapy, need for hospitalization within 30 days, development of CRS and/or neurotoxicity, need for ICU admission, need for steroids and/or tocilizumab, length of admission, and disease state at last follow up. All patients received fludarabine and cyclophosphamide as lymphodepletion (LD) therapy day -5 to -3. CAR T cells were infused on day 0. Patients subsequently followed up in clinic daily for 2 weeks and were started on allopurinol, ciprofloxacin, fluconazole, acyclovir and levetiracetam. First response was assessed by FDG PET scan 4 weeks after CAR T cell . Results A total of 12 patients received CAR T cells during the study period. All patients had a diagnosis of DLBCL and received Tisagenlecleucel. Median age at CAR T cell therapy was 69.5 years (40-78 years). Median number of prior lines of therapy was (2-3) while 2 patients had received prior stem cell transplantation. Table 1 describes patient characteristics and lines of therapy. Two patients received bridging therapy prior to LD. Overall response rate was 58.3% (complete response-3, partial response-4). Median duration of follow up was 6.7 (0.6-13.8 months). Four patients required subsequent therapy after CAR T cell for disease progression while 9 patients were alive at the time of data cut off. Figure 1 summarizes disease response and follow . Table 2 summarizes complications during follow up. Nine (75%) patients developed anemia (grade 3-4 n=4, 33.3%), 8 (66.7%) developed thrombocytopenia (grade 3-4 n= 3, 37.5%), and 8 (66.7%) developed neutropenia (grade 3-4 n=8, 66.7%). Median time to platelet recovery to &gt;,000 and neutrophil recovery to &gt;500 was 66 days (44-81 days) and 11.5 days (6-65 days), respectively. Three (25%) patients required platelet and red blood cell transfusion support. Six (50%) patients developed cytokine release syndrome (CRS) with median grade 2 (range 1-3, grade 3-4 n=1). Five (5/6) patients required hospitalization, five (5/6) required tocilizumab, and one (1/6) required steroids. One (8.3%) patient developed neurotoxicity of grade 1 severity improved without systemic therapy. Six patients required hospitalization within 30 days of CAR T cell infusion. Median day of admission from CAR T cell infusion was 4 days (range 2-12 days (range 2-12 days, admission within 3 days n=2, admission under observation n=1). Patient characteristics at admission are summarized in table 3. Of these, 5 patients were diagnosed with CRS,1 patient with colitis and none with blood stream infection. Two patients required ICU admission. Median length of hospital admission was 5.5 days (2-9 days). All patients were alive at discharge while 1 patient required subsequent admission within 30 . Conclusion Outpatient administration of Tisagenlecleucel is feasible with low risk of hospital admission within 3 days of infusion. Adoption of outpatient CAR T cell therapy may increase patient access for treatment of DLBCL and diseases such as multiple myeloma while reducing administration costs for this novel therapy. Figure 1 Figure 1. Disclosures Modi: Genentech: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees. Deol: Kite, a Gilead Company: Consultancy.

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