EFFICACY AND SAFETY OF CILTACABTAGENE AUTOLEUCEL (CILTA-CEL), A BCMA-DIRECTED CAR-T CELL THERAPY, IN PATIENTS WITH PROGRESSIVE MULTIPLE MYELOMA (MM) AFTER 1–3 PRIOR LINES OF THERAPY: CARTITUDE-2 PHASE 2 STUDY

Objectives: Cilta-cel is a CAR-T cell therapy that expresses 2 BCMA-targeting single-domain antibodies, designed to confer avidity. In the multicohort, phase 2 CARTITUDE-2 study (NCT04133636), the safety and efficacy of cilta-cel in various clinical settings and suitability of outpatient administration was explored in patients with multiple myeloma. Material and methods: Patients enrolled in Cohort A had progressive MM after 1–3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and were naïve to BCMA-targeting agents. A single cilta-cel infusion (target dose: 0.75 × 106 CAR+ viable T cells/kg) was given 5–7 days after start of lymphodepletion (daily cyclophosphamide [300 mg/m2] and fludarabine [30 mg/m2] for 3 days). The primary outcome was minimal residual disease (MRD) 10-5 negativity. Secondary outcomes were response rates (per IMWG criteria) and safety (per CTCAE;CRS and ICANS by ASTCT). Results: As of the February 2021 data cutoff (median follow-up: 5.8 months [2.5–9.8]), 20 patients (65% male;median age 60 years [38–75]) received cilta-cel;1 patient was treated in an outpatient setting. Patients (n = 12: <3 prior LOT;n = 8: 3 prior LOT) received a median of 2 (1–3) prior LOT. All patients were exposed to PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab. The majority (95%) were refractory to the last LOT;40% were triple-class refractory. Overall response rate was 95% (95% CI: 75–100), 75% (95% CI: 51–91) achieved stringent CR/CR, and 85% (95% CI: 62–97) achieved ≥VGPR. Median time to first response was 1.0 month (0.7–3.3);median time to best response was 1.9 month (0.9–5.1). Median duration of response was not reached. All patients (n = 4) with MRD-evaluable samples at 10-5 at data cutoff were MRD-negative. Hematologic AEs ≥20% were neutropenia (95%;grade 3/4: 90%), thrombocytopenia (80%;grade 3/4: 35%), anemia (65%;grade 3/4: 40%), lymphopenia (60%;grade 3/4: 55%), and leukopenia (55%;all grade 3/4). 85% of patients had CRS;10% were grade 3/4. Median time to CRS onset was 7 days (5–9), with a median duration of 3.5 days (2–11). CAR-T cell neurotoxicity occurred in 20% of patients (all grade 1/2). Three patients had ICANS (n = 1: grade 1;n = 2: grade 2);median time to onset was 8 days (7–11) and median duration was 2 days (1–2). One patient had grade 2 facial paralysis;time to onset was 29 days with a duration of 51 days. One death occurred due to Covid-19 (assessed as treatment-related by investigator). The safety profile was manageable in the patient who was treated in an outpatient setting. Discussion: Updated efficacy and safety findings will inform suitability of outpatient treatment in this and other cohorts of CARTITUDE-2 as well as the CARTITUDE-4 study. Conclusion: A single cilta-cel infusion at the recommended phase 2 dose led to early and deep responses with a manageable safety profile in patients with MM who had 1–3 prior LOT.

Anti-BCMA-CAR-T-Zell-Therapie bei einem Patienten mit rezidiviertem und refraktärem Multiplen Myelom nach einer COVID-19-Infektion: ein Fallbericht

Hintergrund: Über das Risiko einer Virusinfektion mit dem schweren akuten Atemwegssyndrom Coronavirus 2 (SARS-CoV-2) bei Krebspatienten, von denen viele immungeschwächt und damit anfälliger für eine Vielzahl von Infektionen sind, ist sehr wenig bekannt. Als Vorsichtsmaßnahme haben viele klinische Studien während der ersten Welle der weltweiten Pandemie des neuartigen Coronavirus (COVID-19) die Aufnahme von Patienten pausiert. In diesem Fallbericht beschreiben wir die erfolgreiche Behandlung eines Patienten mit rezidiviertem und refraktärem Multiplem Myelom (MM), der unmittelbar nach der klinischen Genesung von COVID-19 mit einer chimären Antigenrezeptor (CAR)-T-Zelltherapie mit Anti-B-Zellreifungsantigen (BCMA) behandelt wurde. Fallvorstellung: Der 57-jährige weiße männliche Patient war seit 4 Jahren an MM erkrankt und galt bei der Vorstellung zur CAR-T-Zelltherapie als pentarefraktär. Er hatte eine Immunsuppression in seiner medizinischen Vorgeschichte und er erhielt am Tag vor der COVID-19-Diagnose eine Dosis lymphdepletierender Chemotherapie (LDC). Dieser Patient konnte eine erhebliche Immunantwort gegen das SARS-CoV-2-Virus aufbauen, und antivirale Antikörper bleiben auch 2 Monate nach Erhalt einer Anti-BCMA-CAR-T-Zelltherapie noch nachweisbar. Die kürzliche SARS-CoV-2-Infektion bei diesem Patienten führte nicht zu einer Exazerbation des CAR-T-assoziierten Zytokin-Freisetzungssyndroms (CRS) und umgekehrt führte die CAR-T-Zelltherapie nicht zu Komplikationen im Zusammenhang mit COVID-19. Einen Monat nach der CAR-T-Zell-Infusion wurde bei dem Patienten ein unbestätigtes partielles Ansprechen nach den Kriterien der International Myeloma Working Group (IMWG) festgestellt. Schlussfolgerung: Unser Fall liefert einen wichtigen Kontext für die Wahl der Behandlung von MM-Patienten in Zeiten von COVID-19 sowie für die Frage, ob die CAR-T-Therapie auch bei Patienten verabreicht werden kann, die von COVID-19 genesen sind. Da die COVID-19-Pandemie weltweit anhält, ist eine umfangreiche Diskussion über die Entscheidung, ob mit der CAR-T-Zelltherapie fortgefahren werden soll, erforderlich, wobei die potenziellen Risiken und Vorteile der Therapie gegeneinander abgewogen werden müssen. Dieser Fall legt nahe, dass es möglich ist, die Anti-BCMA-CAR-T-Zelltherapie nach der Genesung von COVID-19 erfolgreich abzuschließen. Die Studie CRB-402 wurde am 6. September 2017 bei clinicaltrials.gov registriert (NCT03274219).

Anti-gm-csf monoclonal antibody gimsilumab improved ventilator-free survival, decreased hospitalization length, and prevented nt-probnp rise in invasively ventilated patients with hyperinflammatory covid19 pneumonia: A subgroup analysis from the breathe trial suggests neurohormonal role for gm-csf inhibition

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF), a myeloid cell growth factor and pro-inflammatory cytokine, may drive the overactive host immune response in COVID-19. We conducted a clinical trial assessing the anti-GM-CSF monoclonal antibody gimsilumab for hyperinflammatory COVID-19 pneumonia (BREATHE). Here, we report a pre-specified subgroup analysis demonstrating a signal of benefit in patients invasively ventilated at baseline. Methods: BREATHE (NCT04351243) was a double-blind, randomized, placebo-controlled trial at 21 US locations. Patients were randomized 1:1 to receive two doses of IV gimsilumab or placebo one week apart. The study included hospitalized COVID-19 patients with hyperinflammation (CRP ≥50 mg/L or ferritin ≥1,000 ng/mL) and pre-ARDS lung injury or ARDS. The primary endpoint was all cause mortality at day 43, and key secondary outcomes assessed ventilator use and hospitalization length. Results: 225 patients were randomized and dosed. 41 patients were invasively ventilated at baseline. Steroid use and baseline characteristics were generally balanced across study arms in this subgroup. Ventilated patients treated with gimsilumab demonstrated improvements over placebo on the primary and key secondary endpoints (Table 1). Contrasting the placebo group, gimsilumabtreated patients did not experience a sharp rise in NT-proBNP, a marker of heart failure, through day 43 (Figure 1). Conclusions: GM-CSF inhibition may be therapeutic in ventilated COVID-19 patients through a neurohormonal mechanism. More studies are needed to assess the role of GM-CSF in COVID-19-associated cardiomyopathy, volume status, and ARDS.

OAB-023: Efficacy and safety of ciltacabtagene autoleucel, a BCMA-directed CAR-T cell therapy, in patients with progressive multiple myeloma after 1–3 prior lines of therapy: Initial results from CARTITUDE-2

Background: Ciltacabtagene autoleucel (cilta-cel) is a CAR-T cell therapy expressing two B-cell maturation antigen (BCMA)-targeting, single-domain antibodies. The multicohort, phase 2 CARTITUDE-2 study (NCT04133636) is evaluating the safety and efficacy of cilta-cel in various clinical settings for patients (pts) with multiple myeloma (MM) and exploring suitability of outpatient administration. Initial results from Cohort A are presented here. Methods: Pts from Cohort A had progressive MM after 1–3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and had not received BCMA-targeting agents. A single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg) was given 5–7 days after start of lymphodepletion (daily cyclophosphamide [300 mg/m2] and fludarabine [30 mg/m2] for 3 days). Minimal residual disease (MRD) negativity at 10-5 was the primary objective, and response rates (per IMWG) and safety (per CTCAE;CRS and ICANS by ASTCT) were secondary outcomes. Results: At data cutoff (Feb 2021), the median follow-up was 5.8 months (2.5–9.8). Twenty pts (65% male;median age 60 years [38–75]) had received cilta-cel, with 1 pt treated in an outpatient setting. The median number of prior LOT was 2 (1–3): <3 prior LOT (n=12) and 3 prior LOT (n=8). All pts were exposed to PI, IMiD, and dexamethasone, 95% had received alkylating agents, and 65% had received daratumumab. 95% were refractory to the last LOT, and 40% were triple-class refractory. Overall response rate was 95% (95% CI: 75–100), 75% (95% CI: 51–91) achieved sCR/CR, and 85% (95% CI: 62–97) achieved ≥VGPR. Median time to first response was 1.0 month (0.7–3.3), and median time to best response was 1.9 months (0.9–5.1). Median duration of response was not reached. All 4 pts with MRD-evaluable samples at 10-5 at the time of data cutoff were MRD-negative. Hematologic adverse events (≥20%) were neutropenia (95%;grade [gr] 3/4: 90%), thrombocytopenia (80%;gr 3/4: 35%), anemia (65%;gr 3/4: 40%), lymphopenia (60%;gr 3/4: 55%), and leukopenia (55%;all gr 3/4). 85% of pts had CRS (gr 3/4: 10%). Median time to CRS onset was 7 days (5–9), with a median duration of 3.5 days (2–11). CAR-T cell neurotoxicity occurred in 20% of pts (all gr 1/2). ICANS was reported in 3 pts (1 gr 1 and 2 gr 2) with median time to onset of 8 days (7–11) and median duration of 2 days (1–2). One pt had gr 2 facial paralysis with onset at 29 days and duration of 51 days. One death from COVID-19 was assessed as treatment-related by investigator. For the pt treated in an outpatient setting, the safety profile was manageable. Conclusion: Early and deep responses with manageable safety were demonstrated after a single cilta-cel infusion at the recommended phase 2 dose. Updated findings will inform suitability of outpatient treatment for this study and for the CARTITUDE-2 and CARTITUDE-4 studies.

Efficacy and safety of the BCMA-directed CAR-T CELL therapy, ciltacabtagene autoleucel, in patients with progressive multiple myeloma after 1-3 prior lines of therapy: Initial results from cartitude-2

Background: Ciltacabtagene autoleucel (Cilta-cel) is a chimeric antigen receptor T (CAR-T) cell therapy expressing two B-cell maturation antigen (BCMA)-targeting, single-domain antibodies designed to confer avidity. CARTITUDE-2 (NCT04133636) is a multicohort, phase 2 study evaluating cilta-cel safety and efficacy in various clinical settings for patients with multiple myeloma (MM) and exploring suitability of outpatient administration. Aims: We report initial results from Cohort A of CARTITUDE-2. Methods: All patients provided informed consent. Patients from Cohort A had progressive MM after 1-3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and had no prior exposure to BCMA-targeting agents. A single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg) was given 5-7 days after initiating lymphodepletion (cyclophosphamide [300 mg/m2] and fludarabine [30 mg/m2] daily for 3 days). The primary objective was minimal residual disease (MRD) 10-5 negativity. Secondary outcomes were response rates per International Myeloma Working Group criteria and safety (adverse events [AEs] were graded per Common Terminology Criteria for Adverse Events;cytokine release syndrome [CRS] and immune effector cell?associated neurotoxicity syndrome [ICANS] were graded per American Society for Transplantation and Cellular Therapy). Results: At the data cutoff of Feb 2021 (median follow-up of 5.8 months;range: 2.5-9.8), 20 patients (65% male;median age 60 years [range: 38-75]) had received cilta-cel;one patient was treated in an outpatient setting. Patients received a median of 2 prior LOT (range: 1-3);12 patients received <3 prior LOT and 8 received 3 prior LOT. All patients were exposed to PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab. The majority (95%) were refractory to their last LOT, and 40% were triple refractory. The overall response rate was 95% (95% CI: 75-100) with 75% (95% CI: 51-91) achieving ≥complete response, and 85% (95% CI: 62-97) achieving ≥very good partial response. Median time to first response was 1.0 month (range: 0.7-3.3), and median time to best response was 1.9 months (range: 0.9-5.1). The median duration of response was not reached. All patients (n=4) with MRD-evaluable samples at 10-5 at the time of data cutoff were MRDnegative. Hematologic AEs (in ≥20% of patients) were neutropenia (95%;grade 3/4: 90%), thrombocytopenia (80%;grade 3/4: 35%), anemia (65%;grade 3/4: 40%), lymphopenia (60%;grade 3/4: 55%), and leukopenia (55%;all grade 3/4). CRS occurred in 85% of patients;10% were grade 3/4. The median time to CRS onset was 7 days (range: 5-9), with a median duration of 3.5 days (range: 2-11). CAR-T cell neurotoxicity occurred in 20% of patients (all grade 1/2). Three patients had ICANS (1 was grade 1;2 were grade 2) with median time to onset of 8 days (range: 7-11) and median duration of 2 days (range: 1-2). One patient had grade 2 facial paralysis with time to onset of 29 days and duration of 51 days. One death occurred due to COVID-19, which was assessed as treatment-related by investigator. The safety profile was manageable in the patient treated in an outpatient setting. Summary/Conclusion: A single cilta-cel infusion at the recommended phase 2 dose led to early and deep responses with manageable safety in patients with MM who had received 1-3 prior LOT. Updated efficacy and safety findings will inform suitability of outpatient treatment in this and other cohorts of CARTITUDE-2 as well as the CARTITUDE-4 study.

REGN5458, a BCMA x CD3 Bispecific Monoclonal Antibody, Induces Deep and Durable Responses in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

Background Multiple myeloma (MM) is characterized by expression of the cell surface protein B-cell maturation antigen (BCMA), a validated target for therapeutic intervention. REGN5458 is a BCMA x CD3 bispecific antibody (Ab) that binds to both BCMA and CD3, thereby targeting MM cells with T-cell effector function via BCMA. Previously, we presented data showing REGN5458 has an acceptable safety profile with evidence of clinical efficacy in heavily pre-treated patients with RRMM. Here we describe the updated safety and response durability in a Phase 1 trial of REGN5458 monotherapy in patients with RRMM (NCT03761108). Methods The primary objectives of the Phase 1 portion of the study are to determine the safety, tolerability, and occurrence of dose-limiting toxicities (DLTs) of REGN5458. Key secondary objectives include assessment of objective response rate (ORR), duration of response (DOR), minimum residual disease (MRD) status, pharmacokinetics (PK), and pharmacodynamics. Enrollment into the Phase 1 portion follows a standard 4+3 dose escalation design. Enrolled patients must have progressive MM after ≥3 prior lines of systemic therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 Ab. Treatment consists of weekly doses of REGN5458, followed by a maintenance phase administered every 2 weeks. Response assessments are according to modified International Myeloma Working Group criteria. MRD is assessed by flow cytometry. Results As of the June 15, 2020 data cut-off, 45 patients were treated with REGN5458. The median age at enrollment was 64.0 years (range, 41−81), of which 14 (31.1%) patients were >70 years. As per Revised International Staging System, 60.0% and 22.2% of patients were stage 2 and 3, respectively. Patients had a median of 5.0 (range, 2−17) prior lines of systemic therapy;32 patients (71.1%) received a prior autologous stem cell transplant. All patients were refractory to an anti-CD38 Ab;6.7% were triple-refractory, 33.3% were quad-refractory, and 53.3% were penta-refractory. REGN5458 was escalated in cohorts from 3−96 mg over six dose levels. The median duration of follow-up was 2.37 months (range, 0.7−12.3). The most common treatment-related adverse events (TRAEs) include cytokine release syndrome (CRS;37.8%), fatigue (17.8%), nausea (17.8%), and myalgias (13.3%). CRS occurred primarily during the initial doses and was Grade (Gr) 1 in 88.2% of patients. No patients had Gr >3 CRS. Infusion-related reactions occurred in 6.7% of patients. Infection-related adverse events (AEs) occurred in 46.7% of patients (Gr ≥3 20%). Gr >3 treatment-related neurological events occurred in one patient (Gr 3 syncope 130 days after first infusion). Four patients discontinued due to AE with one patient having a TRAE (also DLT) of Gr 4 acute kidney injury. One patient had a DLT due to transient Gr 3 liver transaminases associated with CRS. Upon recovery, the patient continued study drug and has achieved ongoing partial remission. Gr >3 TRAEs occurred in 28.9% of patients, with the most common being anemia (8.9%) and lymphopenia (6.7%). Serious TRAEs occurred in 22.2% of patients, with the most common due to CRS (11.1%). Gr 5 AEs (all unrelated to study drug) occurred in three patients: two sepsis and one COVID-19. ORR was 35.6% across all dose levels (60% in highest dose level), with 81.3% of responders achieving at least a very good partial response;31.3% had a complete response (CR) or stringent CR. A total of 43.8% of responders had a DOR >4 months and 18.8% had a DOR >8 months. The ORR in patients with extramedullary plasmacytomas was 16.7%. Additional efficacy, PK, and biomarker data will be available at the time of presentation. Conclusions In this updated analysis of the first-in-human study, REGN5458 continues to show an acceptable safety profile and durable efficacy in heavily pre-treated patients with RRMM. Enrollment in the Phase 1 dose escalation portion is ongoing, and the Phase 2 portion of the study is recruiting. Disclosures: Madduri: Janssen: Consultancy, Honora ia;Foundation Medicine: Consultancy, Honoraria;Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau;Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau;GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau;AbbVie: Consultancy, Honoraria;Takeda: Consultancy, Honoraria;Celgene: Consultancy, Honoraria. Brayer: Janssen: Consultancy;Bristol-Myers Squibb, WindMIL Therapeutics: Research Funding;Bristol-Myers Squibb, Janssen, Amgen: Speakers Bureau. Zonder: Prothena: Consultancy;BMS: Consultancy, Research Funding;Caelum: Consultancy;Oncopeptide: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees;Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees;Janssen: Consultancy, Other: Personal fees;Alnylam: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees;Intellia: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees;Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees;Celgene: Research Funding. Bensinger: Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau;Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau;Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau;Regeneron Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees;GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau;BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau. Li: Regeneron Pharmaceuticals, Inc: Current Employment, Current equity holder in publicly-traded company. Xu: Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Adriaens: Regeneron Pharmaceuticals, Inc: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: Dosing regime that mitigates cytokine release syndrome for therapeutic antibodies (status: pending). Chokshi: Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Zhang: Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Boyapati: Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Sharma: Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Seebach: Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Sirulnik: Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Weinreich: Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Yancopoulos: Regeneron Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. Dhodapkar: Amgen: Membership on an entity's Board of Directors or advisory committees, Other;Kite: Membership on an entity's Board of Directors or advisory committees, Other;Janssen: Membership on an entity's Board of Directors or advisory committees, Other;Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Other;Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Other;Lava Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other. Lentzsch: Mesoblast: Divested equity in a private or publicly-traded company in the past 24 months;Caelum Biosciences: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees;Celularity: Consultancy, Other;Janssen: Consultancy;Karyopharm: Research Funding;Magenta: Current equity holder in private company. Jagannath: MS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy. OffLabel Disclosure: The data described in the abstract will report on use of REGN5458 in a first-in-human trial in patients with multiple myeloma.

CARTITUDE-2: Efficacy and safety of ciltacabtagene autoleucel (ciltacel), a BCMA-directed CAR T-cell therapy, in patients with progressive multiple myeloma (MM) after one to three prior lines of therapy

Background: Cilta-cel is a CAR T-cell therapy expressing two BCMA-targeting, single-domain antibodies designed to confer avidity. The multicohort, phase 2 CARTITUDE-2 study (NCT04133636) is evaluating cilta-cel safety and efficacy in various clinical settings for patients (pts) with MM and exploring suitability of outpatient administration. Here, we present initial results from Cohort A. Methods: Cohort A pts had progressive MM after 1-3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and had no prior exposure to BCMA-targeting agents. A single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg) was given 5-7 days (d) after start of lymphodepletion (daily cyclophosphamide [300 mg/m2 ] and fludarabine [30 mg/m2 ] for 3 d). The primary objective was minimal residual disease (MRD) 10 negativity. Secondary outcomes were response rates (IMWG) and safety (per CTCAE;CRS and ICANS by ASTCT). Results: As of Feb 2021 data cutoff (median follow-up: 5.8 months [mo];range: 2.5-9.8 mos), 20 pts (65% male;median age 60 years [38-75]) received cilta-cel;1 pt was treated in an outpatient setting. Pts received a median of 2 prior LOT (1-3);12 pts received < 3 prior lines and 8 received 3 prior LOT. All pts were exposed to PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab. The majority (95%) were refractory to the last LOT;40% were triple refractory. Overall response rate was 95% (95% CI: 75-100), 75% (95% CI: 51-91) achieved stringent CR/CR, and 85% (95% CI: 62-97) achieved ≥VGPR. Median time to first response was 1.0 mo (0.7-3.3);median time to best response was 1.9 mo (0.9-5.1). Median duration of response was not reached. All pts (n = 4) with MRD-evaluable samples at 10 at data cutoff were MRD-negative. Hematologic AEs ≥20% were neutropenia (95%;gr 3/4: 90%), thrombocytopenia (80%;gr 3/4: 35%), anemia (65%;gr 3/4: 40%), lymphopenia (60%;gr 3/4: 55%), and leukopenia (55%;all gr 3/4). CRS occurred in 85% of pts;10% were gr 3/4. Median time to CRS onset was 7 d (5-9), with a median duration of 3.5 d (2-11). CAR T-cell neurotoxicity occurred in 20% of pts (all gr 1/2). Three pts had ICANS (1 gr 1;2 gr 2);median time to onset was 8 d (7-11) and median duration was 2 d (1-2). One pt had gr 2 facial paralysis;time to onset was 29 d with a duration of 51 d. One death occurred due to COVID-19 (assessed as treatment (tx)-related by investigator). Safety profile was manageable in the pt treated in an outpatient setting. Conclusions: A single cilta-cel infusion at the recommended phase 2 dose led to early and deep responses with a manageable safety profile in pts with MM who had 1-3 prior LOT. Updated efficacy and safety findings will inform suitability of outpatient tx in this and other cohorts of CARTITUDE-2 as well as the CARTITUDE-4 study.

Anti-BCMA CAR T administration in a relapsed and refractory multiple myeloma patient after COVID-19 infection: a case report.

BACKGROUND: Very little is known about the risk that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection poses to cancer patients, many of whom are immune compromised causing them to be more susceptible to a host of infections. As a precautionary measure, many clinical studies halted enrollment during the initial surge of the global Novel Coronavirus Disease (COVID-19) pandemic. In this case report, we detail the successful treatment of a relapsed and refractory multiple myeloma (MM) patient treated with an anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy immediately following clinical recovery from COVID-19. CASE PRESENTATION: The 57 year old Caucasian male patient had a 4-year history of MM and was considered penta-refractory upon presentation for CAR T cell therapy. He had a history of immunosuppression and received one dose of lymphodepleting chemotherapy (LDC) the day prior to COVID-19 diagnosis; this patient was able to mount a substantial immune response against the SARS-CoV-2 virus, and antiviral antibodies remain detectable 2 months after receiving anti-BCMA CAR T cell therapy. The recent SARS-CoV-2 infection in this patient did not exacerbate CAR T-associated cytokine release syndrome (CRS) and conversely the CAR T cell therapy did not result in COVID-19-related complications. One month after CAR T cell infusion, the patient was assessed to have an unconfirmed partial response per International Myeloma Working Group (IMWG) criteria. CONCLUSION: Our case adds important context around treatment choice for MM patients in the era of COVID-19 and whether CAR T therapy can be administered to patients who have recovered from COVID-19. As the COVID-19 global pandemic continues, the decision of whether to proceed with CAR T cell therapy will require extensive discussion weighing the potential risks and benefits of therapy. This case suggests that it is possible to successfully complete anti-BCMA CAR T cell therapy after recovery from COVID-19. CRB-402 study registered 6 September 2017 at clinicaltrials.gov (NCT03274219).

MM-239: A Tertiary Center Experience of Multiple Myeloma Patients with COVID-19: Lessons Learned and the Path Forward

Context: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in over 100,000 deaths in the United States. Our institution has treated over 2,000 COVID-19 patients during the pandemic in New York City. Objective: We explored the population of myeloma patients who developed COVID-19 to identify risk factors tied to poor outcomes. Design: We performed a retrospective study of a cohort of 58 patients with a plasma cell disorder (54 MM, 4 smoldering MM) who developed COVID-19 between March 1, 2020 and April 30, 2020. We report epidemiological, clinical, and laboratory characteristics, including persistence of viral detection by polymerase chain reaction (PCR) and anti-SARS-CoV-2 antibody testing, treatments initiated, and outcomes. Setting: A large tertiary care cancer center in New York at the epicenter of the COVID-19 pandemic in the USA. Patients: Patient charts were analyzed retrospectively. Patients had MM or SMM and COVID-19. Results: Of the 58 patients diagnosed with COVID-19, 36 were hospitalized and 22 were managed at home. The median age was 67 years;52% of patients were male, and 63% were non-white. Hypertension (64%), hyperlipidemia (62%), obesity (37%), diabetes mellitus (28%), chronic kidney disease (CKD, 24%), and lung disease (21%) were the most common comorbidities. In the total cohort, 14 patients (24%) died. Older age (>70 years), male sex, and cardiovascular risk were significantly (p < 0.05) associated with hospitalization. Among hospitalized patients, laboratory findings demonstrated elevation of traditional inflammatory markers (CRP, ferritin, D-dimer) and a significant (p < 0.05) association between elevated inflammatory markers, severe hypogammaglobulinemia, non-white race, and mortality. Ninety-six percent (22/23) of patients developed antibodies to SARS-CoV-2 at a median of 32 days after initial diagnosis. Median time to PCR negativity was 43 (range 19–68) days from initial positive PCR. Conclusions: Drug exposure and MM disease status at the time of contracting COVID-19 had no bearing on patient outcome. Mounting a severe inflammatory response to SARS-CoV-2 and severe hypogammaglobulinemia were associated with higher mortality. These findings pave a path to the identification of vulnerable patients who need early intervention to improve outcomes of myeloma patients in future outbreaks of COVID-19. The majority of myeloma patients mounted a specific antibody response to SARS-CoV-2.