DREAMM-9: PHASE I STUDY OF BELANTAMAB MAFODOTIN PLUS STANDARD OF CARE IN PATIENTS WITH TRANSPLANT-INELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA

Background: The bortezomib, lenalidomide, and dexamethasone (VRd) regimen is a standard of care for newly diagnosed multiple myeloma (NDMM). Belantamab mafodotin (belamaf) is a B-cell maturation antigen-binding antibody-drug conjugate that eliminates myeloma cells by a multimodal mechanism: direct cell kill and anti-myeloma tumor immune response. Belamaf has demonstrated deep and durable responses as a monotherapy in the DREAMM-2 study of patients (pts) with relapsed/refractory multiple myeloma (RRMM). Preclinical evidence of belamaf in combination with bortezomib or lenalidomide suggests enhanced anti-myeloma activity, providing rationale for this treatment combination. Aims: To evaluate the safety and tolerability of this combination in adult pts with transplant-ineligible (TI) NDMM and establish the recommended Phase III dose. Methods: DREAMM-9 (NCT04091126) is an ongoing Phase I, open-label, randomized study of belamaf + VRd. The belamaf dose cohorts currently being evaluated are Cohort 1 (1.9 mg/kg Q3/4W), Cohort 2 (1.4 mg/kg Q6/8W), Cohort 3 (1.9 mg/kg Q6/8W), Cohort 4 (1.0 mg/kg Q3/4W), and Cohort 5 (1.4 mg/kg Q3/4W). Belamaf is given with VRd Q3W until Cycle 8, and with Rd Q4W thereafter. After evaluation of safety data for Cohort 1, Cohorts 2-5 were opened in parallel and enrolled pts were randomized 1:1:1:1. Primary endpoint is safety. Secondary endpoints include efficacy, tolerability, and pharmacokinetics (PK). Results: As of data cutoff (07 Dec 2021), 64 pts were analyzed across all cohorts. Median age (range) was 73.0 (51- 88) years, 55% were male, 80% were white, 8% had extramedullary disease, 59% were International Staging System stage II or III, 20% had amp1q, and 17% had high-risk cytogenetics (≥1 of: t(4;14), t(14;16), del17p). The median duration of follow-up varied: Cohort 1 (17.4 months [mo]), Cohort 2 (5.9 mo), Cohort 3 (6.1 mo), Cohort 4 (4.7 mo), Cohort 5 (5.8 mo). Median number of belamaf cycles were: Cohort 1 (6), Cohort 2 (3), Cohort 3 (3.5), Cohort 4 (4.5), and Cohort 5 (5). Most common adverse events (AEs) across cohorts included thrombocytopenia (49%), constipation (43%), diarrhea (32%), and peripheral sensory neuropathy (30%). AEs related to study treatment were experienced by 61 (97%) pts. Belamaf-related grade 3/4 AEs occurred in 24 (38%) pts. Belamaf dose reductions occurred in 11 (18%) pts, with dose delays in 10 (16%) pts. Three pts experienced a fatal severe AE (unrelated to study treatment);2 due to COVID-19 infection, 1 due to pancreatic adenocarcinoma. Early deep responses were observed;67-92% pts achieved ≥very good partial response (VGPR) (Table), with median time to VGPR of 2.1-2.9 months across cohorts. Of pts with ≥VGPR, 17 were minimal residual disease (MRD) negative, 10 in Cohort 1. As of data cutoff, 8-75% of pts achieved best response of complete response (CR) or stringent CR (sCR). Grade 3 corneal exam findings were reported in 25-58% of pts;grade 3 visual acuity changes were reported in 21-75% of pts. No grade 4 corneal exam findings or visual acuity changes were reported in pts receiving belamaf Q6/8W, compared with 0-17% and 0-8%, respectively, in the Q3/4W cohorts. Belamaf PK profile was similar to that in pts with RRMM, accounting for baseline characteristics. Image: Summary/Conclusion: Belamaf + VRd demonstrated high response rates in pts with TI NDMM, with a high rate of MRD negativity indicating deep responses. No new safety signals were observed relative to DREAMM-2. Study is ongoing to evaluate the safety and efficacy of variable dose intensities of belamaf in combination with VRd.

DREAMM-9: PHASE I STUDY OF BELANTAMAB MAFODOTIN PLUS STANDARD OF CARE IN PATIENTS WITH TRANSPLANT-INELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA

Background: The bortezomib, lenalidomide, and dexamethasone (VRd) regimen is a SoC for NDMM. Belamaf, a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate, demonstrated durable responses in patients with relapsed/refractory multiple myeloma. Preclinical studies of belamaf in combination with bortezomib/ lenalidomide suggest enhanced antimyeloma activity. We report preliminary findings of belamaf + VRd for patients with TI NDMM. Materials and Methods: DREAMM-9 (NCT04091126) is an ongoing Phase I, open label, randomized, dose and schedule evaluation trial. Adults with TI NDMM and ECOG status 0-2 are eligible. VRd is administered Q3W until Cycle 8, followed by lenalidomide + dexamethasone (Rd) Q4W. Belamaf + VRd is administered until Cycle 8, and with Rd thereafter. The currently evaluated belamaf dose cohorts are: Cohort 1 (1.9 mg/kg Q3/4W), Cohort 2 (1.4 mg/kg Q6/8W), Cohort 3 (1.9 mg/ kg Q6/8W), Cohort 4 (1.0 mg/kg Q3/4W), and Cohort 5 (1.4 mg/kg Q3/4W). Primary endpoint is safety. Secondary endpoints include efficacy, tolerability, and pharmacokinetics (PK). Results: Overall 36 patients were treated across the 5 cohorts. The median (range) age was 74.0 (63-80) years;56% patients were male, 17 (47%) had stage 2 disease, 3 (8%) had extramedullary disease, 6 (17%) patients had high risk cytogenetic abnormalities;the median number of belamaf cycles ranged from 1-9. No new safety signals were observed. Across Cohorts 1-5, all patients experienced AEs related to study treatment;1 patient in Cohort 1 died due to COVID-19 infection. The most common AEs leading to dose modification were thrombocytopenia, neutropenia, and corneal events. Patients in Cohort 2 and 3 had the lowest number of Grade ≥3 corneal events (3 and 2 events, respectively). All 12 patients in Cohort 1, all 6 in Cohorts 3 and 5, and 5/6 patients in Cohorts 2 and 4 have responded to the treatment;≥half of patients in each cohort achieved very good partial response or better. As of data cut-off, 3/12 patients in Cohort 1, 2/6 in Cohort 4, and 1/6 patients each in Cohorts 3 and 5 remained in complete response. Belamaf PK profile was similar to that observed in patients with RRMM taking into consideration baseline patients characteristics. Conclusions: Preliminary data suggest addition of belamaf to VRd did not reveal new safety signals and demonstrates high response rates, albeit with short follow-up. The trial is ongoing to confirm safety and evaluate the efficacy of belamaf + VRd. .

TALQUETAMAB, A G PROTEIN-COUPLED RECEPTOR FAMILY C GROUP 5 MEMBER D X CD3 BISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): UPDATED PHASE 1 RESULTS FROM MONUMENTAL-1

G protein-coupled receptor family C group 5 member D (GPRC5D) has limited expression in healthy human tissue but is highly expressed in malignant plasma cells, making it a promising target for immunotherapy approaches for MM. Talquetamab (JNJ-64407564) is a first-in-class bispecific antibody that binds to both GPRC5D and CD3 receptors to redirect T cells to kill MM cells. Updated and new results of talquetamab at the recommended phase 2 doses (RP2Ds) are reported (NCT03399799). Eligible patients had RRMM or were intolerant to standard therapies. Patients who were previously treated with B-cell maturation antigen (BCMA)-directed therapies were eligible. This analysis focuses on patients who received talquetamab subcutaneously (SC;range: 5.0-800 μg/kg) weekly (QW) or biweekly (Q2W) with step-up dosing. The primary objectives were to identify the RP2D (part 1) and assess talquetamab safety and tolerability at the RP2Ds (part 2). Adverse events (AEs) were graded by CTCAE v4.03;cytokine release syndrome (CRS) was graded per Lee et al 2014 criteria. Responses were investigator-assessed per IMWG criteria. As of July 19, 2021, 95 patients had received SC talquetamab. The original RP2D was 405 μg/kg SC talquetamab QW with step-up doses, and a second RP2D of 800 μg/kg SC talquetamab Q2W with step-up doses was also identified. 30 patients received 405 μg/kg QW (median 61.5 years [range 46-80];63% male;100% triple-class exposed;80% penta-drug exposed;77% triple-class refractory, 20% penta-drug refractory;30% prior BCMA-directed therapy;median follow-up [mF/U]: 7.5 mo [range 0.9-15.2]). 23 patients received 800 μg/kg Q2W (median 60.0 years [range 47-84];48% male;96% triple-class exposed;70% penta-drug exposed;65% triple-class refractory, 22% penta-drug refractory;17% prior BCMA-directed therapy;mF/U: 3.7 mo [range 0.0-12.0]). No treatment discontinuations due to AEs were reported at either RP2Ds. Most common AEs at the 405 μg/kg QW were CRS (73%;1 grade 3 CRS), neutropenia (67%;grade 3/4: 60%), and dysgeusia (60%;grade 2: 29%). Skin-related AEs occurred in 77% of patients and were all grade 1/2 (nail disorders: 30%). Infections occurred in 37% of patients (1 grade 3 COVID-19 pneumonia). Most common AEs at 800 μg/kg Q2W were CRS (78%;all grade 1/2), dry mouth (44%;all grade 1/2), and neutropenia (44%;grade 3/4: 35%). Skin-related AEs occurred in 65% of patients with grade 3 events in 13% (nail disorders: 17%). Infections occurred in 13% of patients (1 grade 3 pneumococcal sepsis). In 30 response-evaluable patients treated at 405 μg/kg QW, the overall response rate (ORR) was 70% (very good partial response or better [≥VGPR]: 57%). In 17 response-evaluable patients treated at 800 μg/ kg Q2W, the ORR was 71% (≥VGPR: 53%). Responses were durable and deepened over time with both RP2Ds (Figure). Median duration of response (DOR) was not reached at either RP2D;6-month DOR rate was 67% (95% CI: 41-84) at 405 μg/kg QW. Serum trough levels of talquetamab were comparable at both RP2Ds. Pharmacodynamic data at both RP2Ds showed peripheral T cell activation and induction of cytokines. SC talquetamab is well tolerated and highly effective at both RP2Ds. Preliminary data suggest that less frequent, higher doses of SC talquetamab do not negatively impact the safety profile. Further evaluation of talquetamab as monotherapy (phase 2;NCT04634552) and in combination with other therapies in patients with RRMM is underway. (Figure Presented) .

Updated Phase 1 Results from MonumenTAL-1: First-in-Human Study of Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma

Introduction: Despite recent advances in treatment, patients with multiple myeloma (MM) continue to relapse. G protein-coupled receptor family C group 5 member D (GPRC5D) is a promising target for immunotherapy in patients with MM due to its high expression in malignant plasma cells and limited expression in normal human tissue;unlike other antigens targeted by MM therapies, there is no indication that GPRC5D sheds into the periphery. Talquetamab (JNJ-64407564) is a first-in-class bispecific IgG4 antibody that redirects T cells to kill MM cells by binding to both GPRC5D and CD3 receptors. Here we report updated and new results of talquetamab at the recommended phase 2 doses (RP2Ds) from a phase 1 trial in relapsed/refractory MM (RRMM;NCT03399799). Methods: Eligible patients with MM had relapsed or refractory disease or were intolerant to standard therapies;patients previously treated with B-cell maturation antigen (BCMA)-directed therapies were eligible. This analysis focuses on patients who received talquetamab subcutaneously (SC;range 5.0-800 µg/kg) weekly or biweekly. Step-up dosing was used as a patient management strategy to minimize the severity of cytokine release syndrome (CRS). The primary objectives were to identify the RP2D (part 1) and assess talquetamab safety and tolerability at the RP2Ds (part 2). Adverse events (AEs) were graded by CTCAE v4.03 with CRS events graded per Lee et al 2014 criteria. Responses were investigator-assessed per International Myeloma Working Group criteria. Results: As of July 19, 2021, 95 patients have received SC talquetamab. The RP2D was originally identified as a weekly SC dose of 405 µg/kg talquetamab with step-up doses. However, alternative dosing schedules that require less frequent administration continue to be investigated. A biweekly RP2D was also identified as an SC dose of 800 µg/kg talquetamab with step-up doses. 30 patients received the 405 µg/kg weekly dosing schedule (median age: 61.5 years [range 46-80];63% male;100% triple-class exposed;80% penta-drug exposed;77% triple-class refractory, 20% penta-drug refractory;30% prior BCMA-directed therapy;median follow-up: 7.5 mo [range 0.9-15.2]). 23 patients received the 800 µg/kg biweekly dosing schedule (median age: 60.0 years [range 47-84];48% male;96% triple-class exposed;70% penta-drug exposed;65% triple-class refractory, 22% penta-drug refractory;17% prior BCMA-directed therapy;median follow-up 3.7 mo [range 0.0-12.0]). There were no treatment discontinuations due to AEs at either of the RP2Ds. The most common AEs at the 405 µg/kg weekly dose were CRS (73%;1 patient had grade 3 CRS), neutropenia (67%;grade 3/4: 60%), and dysgeusia (60%;grade 2: 29%);skin-related AEs occurred in 77% (all grade 1/2;nail disorders: 30%) of patients, and infections occurred in 37% of patients (1 patient had grade 3 COVID-19 pneumonia). The most common AEs at the 800 µg/kg biweekly dose were CRS (78%;all grade 1/2), dry mouth (44%;all grade 1/2), and neutropenia (44%;grade 3/4: 35%);skin-related AEs occurred in 65% of patients (grade 3: 13%;nail disorders: 17%) and infections occurred in 13% of patients (1 patient had grade 3 pneumococcal sepsis). In 30 response-evaluable patients treated with the 405 µg/kg weekly dose, the overall response rate (ORR) was 70% (very good partial response or better [≥VGPR] rate: 57%). In 17 response-evaluable patients treated with the 800 µg/kg biweekly dose, the ORR was 71% (≥VGPR rate: 53%). Responses were durable and deepened over time in both cohorts (Figure). Median duration of response (DOR) was not reached at either RP2D;the 6-month DOR rate for patients who received the 405 µg/kg weekly dose was 67% [95% CI: 41-84]. Serum trough levels of talquetamab were comparable at both RP2Ds. Consistent with the mechanism of action for talquetamab, pharmacodynamic data from cohorts treated at both dose levels showed peripheral T-cell activation and induction of cytokines. Conclusions: These findings indicate that SC talquetamab is well tolerated and highly effective at both RP2Ds. Preliminary data from the 800 µg/kg biweekly cohorts indicate that less frequent, higher doses of SC talquetamab do not have a negative impact on the previously described safety profile. Further investigation of talquetamab as monotherapy (phase 2;NCT04634552) and in combination with other therapies in patients with RRMM is underway. [Formula presented] Disclosures: Krishnan: MAGENTA: Consultancy;BMS: Consultancy, Current equity holder in publicly-traded company, Speakers Bureau;JANSSEN: Consultancy, Research Funding;City of Hope Cancer Center: Current Employment;REGENERON: Consultancy;SANOFI: Consultancy;GSK: Consultancy;Amgen: Speakers Bureau. Minnema: Celgene: Other: Travel expenses;Alnylam: Consultancy;Cilag: Consultancy;BMS: Consultancy;Janssen: Consultancy;Kite/Gilead: Consultancy. Berdeja: Lilly, Novartis: Research Funding;Abbvie, Acetylon, Amgen: Research Funding;Celularity, CRISPR Therapeutics: Research Funding;EMD Sorono, Genentech: Research Funding;Poseida, Sanofi, Teva: Research Funding;Bluebird bio, BMS, Celgene, CRISPR Therapeutics, Janssen, Kite Pharma, Legend Biotech, SecuraBio, Takeda: Consultancy;GSK, Ichnos Sciences, Incyte: Research Funding. Oriol: Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees;GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. van de Donk: Roche: Consultancy;Takeda: Consultancy;Cellectis: Research Funding;Amgen: Consultancy, Research Funding;Janssen: Consultancy, Research Funding;BMS/Celgene: Consultancy, Honoraria;Novartis /bayer/servier: Consultancy. Rodriguez-Otero: Clínica Universidad de Navarra: Current Employment;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene-BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Pfizer: Consultancy;Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Kite: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria;Regeneron: Honoraria. Askari: Janssen: Research Funding. Mateos: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees;Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees;Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Honoraria;Bluebird bio: Honoraria;AbbVie: Honoraria;GSK: Honoraria;Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Costa: BMS: Consultancy, Honoraria, Research Funding;Janssen: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau;Karyopharm: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria;Sanofi: Consultancy, Honoraria, Speakers Burea . Verona: Janssen: Current Employment. Ma: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Girgis: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Yang: Janssen: Current Employment. Hilder: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Russell: Janssen: Ended employment in the past 24 months. Goldberg: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Chari: Shattuck Labs: Consultancy, Membership on an entity's Board of Directors or advisory committees;Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding;Millenium/Takeda: Consultancy, Research Funding;Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees;Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees;Takeda: Consultancy, Research Funding;Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Pharmacyclics: Research Funding;Secura Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees;GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Research Funding;Genentech: Consultancy, Membership on an entity's Board of Directors or advisorycommittees;Janssen Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Iberdomide (IBER) in Combination with Dexamethasone (DEX) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Dose-Expansion Phase of the CC-220-MM-001 Trial

Introduction: Despite recent advances, MM remains incurable and new therapeutic options are needed, particularly for pts with RRMM. IBER is a novel, potent oral cereblon E3 ligase modulator (CELMoD ®) compound with enhanced tumoricidal and immune-stimulatory effects compared with immunomodulatory (IMiD ®) agents. Preclinically, IBER demonstrated marked synergy with DEX and with other standard myeloma treatments. CC-220-MM-001 (NCT02773030) is an ongoing phase 1/2 study evaluating IBER with different treatment combinations in independent cohorts of pts with RRMM;in phase 1, the recommended phase 2 dose of IBER, when given in combination with DEX, was determined at 1.6 mg (Lonial S, et al. Blood 2019;134[suppl 1]:3119). Here we report results from the dose expansion of IBER + DEX in pts with heavily pretreated, triple-class exposed (including ≥ 1 IMiD agent, ≥ 1 proteasome inhibitor [PI], and ≥ 1 anti-CD38 monoclonal antibody [mAb]) RRMM. Methods: Eligible pts had RRMM;had received ≥ 3 prior lines of therapy, including lenalidomide (LEN), pomalidomide (POM), a PI, a glucocorticoid, and an anti-CD38 mAb;had experienced disease progression within 60 days of last myeloma therapy;and were refractory to an IMiD agent, a PI, a glucocorticoid, and an anti-CD38 mAb. Pts with central nervous system involvement were not eligible. Pts who had received prior anti-BCMA therapy were excluded, but included in a supportive cohort for safety and preliminary efficacy assessment. IBER (1.6 mg) was given orally on days (D) 1-21, in combination with DEX (40 mg;20 mg if > 75 years of age) on D1, 8, 15, and 22 of each 28-day cycle. Thrombo-embolism prophylaxis was mandatory for all pts. Primary objective was to determine efficacy expressed as overall response rate (ORR). Secondary endpoints included additional efficacy and safety assessments. Exploratory endpoints included evaluation of health-related quality of life (HRQoL). Results: As of June 2, 2021, 107 pts had received IBER + DEX. Median age was 64 (44-83) years;median time since initial diagnosis was 6.9 (1.6-24.5) years. Extramedullary plasmacytomas were present in 25.2% of pts;29.9% of pts had high-risk cytogenetics. Median number of prior regimens was 6 (3-23). All pts were triple-class exposed;prior therapies included autologous stem cell transplantation (78.5%), PIs (100%), IMiD agents (LEN [100%] and POM [100%]), and anti-CD38 mAbs (100%);99.1% of pts were refractory to last myeloma regimen and 97.2% of pts were triple-class refractory. Median follow-up was 7.69 (0.5-17.5) months, with a median number of 4 (1-17) cycles received and 13 (12.1%) pts continuing treatment. Main reason for discontinuation was progressive disease (69.2%). ORR was 26.2%, with 1 (0.9%) stringent complete response, 8 (7.5%) very good partial responses, and 19 (17.8%) partial responses (Table);the clinical benefit rate (≥ minimal response) was 36.4% and disease control rate (≥ stable disease) was 79.4%. Median duration of response was 7.0 (4.5-11.3) months (Table), median progression-free survival was 3.0 (2.8-3.7) months, and median overall survival was 11.2 (9.0-not reached) months. Similar response rates were observed among a cohort of pts also exposed to BCMA therapies (N = 24, Table). Grade (Gr) 3-4 treatment-emergent adverse events (TEAEs) were reported in 88 (82.2%) pts. Most frequent (≥ 20% pts) hematologic Gr 3-4 TEAEs were neutropenia (44.9%;and 4.7% febrile neutropenia), anemia (28.0%), thrombocytopenia (21.5%), and leukopenia (20.6%). Gr 3-4 infections were reported in 27.1% of pts;Gr 3-4 pneumonia and COVID-19 occurred in 10.3% and 4.7% of pts, respectively. Occurrence of other Gr 3-4 non-hematologic TEAEs was generally low, including gastrointestinal disorders (5.6%), fatigue (2.8%), rash (1.9%). Fifty-six (52.3%) pts and 20 (18.7%) had IBER dose interruptions and reductions due to TEAEs, respectively. Five (4.7%) pts discontinued due to TEAEs. No pt discontinued IBER due to neutropenia. Overall, HRQoL was maintained in these pts. Conclusions: IBER + DEX demonst ated promising efficacy in pts with heavily pretreated, triple-class exposed and refractory RRMM, as well as in pts who had previously received anti-BCMA therapy;this combination was generally well tolerated and TEAEs were manageable with dose reductions and interruptions. These results support the further development of IBER in MM, including phase 3 trials in combination regimens. [Formula presented] Disclosures: Lonial: Abbvie: Consultancy, Honoraria;AMGEN: Consultancy, Honoraria;Takeda: Consultancy, Honoraria, Research Funding;GlaxoSmithKline: Consultancy, Honoraria, Research Funding;TG Therapeutics: Membership on an entity's Board of Directors or advisory committees;Merck: Honoraria;BMS/Celgene: Consultancy, Honoraria, Research Funding;Janssen: Consultancy, Honoraria, Research Funding. Popat: GlaxoSmithKline: Consultancy, Honoraria, Research Funding;Abbvie, Takeda, Janssen, and Celgene: Consultancy;Takeda: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES;AbbVie, BMS, Janssen, Oncopeptides, and Amgen: Honoraria;Janssen and BMS: Other: travel expenses. Hulin: Sanofi: Honoraria;Celgene/BMS: Honoraria;Janssen: Honoraria;Takeda: Honoraria;abbvie: Honoraria. Jagannath: Legend Biotech: Consultancy;Bristol Myers Squibb: Consultancy;Karyopharm Therapeutics: Consultancy;Janssen Pharmaceuticals: Consultancy;Sanofi: Consultancy;Takeda: Consultancy. Oriol: Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees;Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Richardson: Karyopharm: Consultancy, Research Funding;Regeneron: Consultancy;AbbVie: Consultancy;Celgene/BMS: Consultancy, Research Funding;Oncopeptides: Consultancy, Research Funding;GlaxoSmithKline: Consultancy;Protocol Intelligence: Consultancy;Janssen: Consultancy;Secura Bio: Consultancy;Takeda: Consultancy, Research Funding;Sanofi: Consultancy;AstraZeneca: Consultancy;Jazz Pharmaceuticals: Consultancy, Research Funding. Weisel: Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche: Honoraria;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Abbvie: Consultancy;Novartis: Honoraria;Pfizer: Honoraria. Minnema: Cilag: Consultancy;Janssen: Consultancy;Alnylam: Consultancy;Celgene: Other: Travel expenses;Kite/Gilead: Consultancy;BMS: Consultancy. Badros: J&J: Research Funding;Janssen: Research Funding;BMS: Research Funding;GlaxoSmithKline: Research Funding. Knop: BMS/Celgene: Consultancy, Honoraria, Research Funding;Amgen: Research Funding;Janssen: Consultancy;Oncopeptides: Consultancy;Pfizer: Consultancy;Sanofi: Consultanc . Stadtmauer: Janssen: Consultancy, Honoraria;Takeda: Consultancy, Honoraria;Abbvie: Consultancy, Honoraria;Amgen: Consultancy, Honoraria;Bristol Myers Squibb: Consultancy, Honoraria, Research Funding. Chen: Bristol Myers Squibb: Current Employment. Nguyen: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Amin: Bristol Myers Squibb: Current Employment. Kueenburg: Celgene a BMS company: Current Employment. Peluso: Celgene, a Bristol-Myers Squibb Company: Current Employment. van de Donk: BMS/Celgene: Consultancy, Honoraria;Janssen: Consultancy, Research Funding;Amgen: Consultancy, Research Funding;Cellectis: Research Funding;Takeda: Consultancy;Roche: Consultancy;Novartis /bayer/servier: Consultancy.

Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Efficacy and Safety Results of the Phase 3 Candor Study

Introduction: The randomized, open-label, multicenter, phase 3 CANDOR study compared carfilzomib, dexamethasone, and daratumumab (KdD) to carfilzomib and dexamethasone (Kd) in patients with multiple myeloma who have relapsed after 1-3 prior lines of therapy (ClinicalTrials.gov, NCT03158688). In the previously reported primary analysis (Dimopoulos et al, Lancet 2020), a significant progression-free survival (PFS) benefit was demonstrated in patients treated with KdD vs patients treated with Kd (hazard ratio [HR], 0.63 [95% CI, 0.46-0.85];two-sided P=0.0027). However, after a median follow-up of 16.9 months, median PFS was not reached in the KdD arm. Here, we report updated efficacy and safety outcomes from the CANDOR study. Methods: Adult patients with relapsed or refractory multiple myeloma (RRMM) received 28-day cycles of KdD or Kd (randomized 2:1). In the primary analysis, PFS was the primary endpoint and overall survival (OS) a key secondary endpoint. In this prespecified interim OS analysis, statistical testing was based on the actual number of OS events observed by the data cutoff (approximately 36 months after enrollment of the first patient);PFS was summarized descriptively. Disease progression was determined locally by investigators in an unblinded manner and centrally by the sponsor using a validated computer algorithm (Onyx Response Computer Algorithm [ORCA]) in a blinded manner. PFS and OS were compared between the KdD and Kd arms using a stratified log-rank test, and HRs were estimated by a stratified Cox proportional-hazards model. Results: Patients were randomized to KdD (n = 312) and Kd (n = 154). Of all randomized patients, median age was approximately 64 years;42% received previous lenalidomide, and 33% were lenalidomide refractory;90% received previous bortezomib, and 29% were bortezomib refractory. At the data cutoff date of June 15, 2020, 199 (63.8%) patients in the KdD arm and 88 (57.1%) in the Kd arm remained on study. Among patients treated with KdD and Kd, 140 (44.9%) and 85 (55.2%) had PFS events, respectively;median follow-up was 27.8 months (KdD) and 27.0 months (Kd). Median PFS by ORCA was 28.6 months for the KdD arm versus 15.2 months for the Kd arm (HR, 0.59 [95% CI, 0.45-0.78];Figure). OS data were not mature and will be updated at a future prespecified analysis. Median treatment duration was 79.3 weeks with KdD versus 40.3 weeks with Kd. Grade ≥3 adverse events (AEs) occurred in 87.0% and 75.8% of patients in the KdD and Kd arms, respectively, and fatal AEs occurred in 8.8% and 4.6%;one fatal AE in the KdD arm (due to arrhythmia) and one fatal AE in the Kd arm (due to COVID-19 pneumonia) had occurred since the primary analysis. Carfilzomib treatment discontinuation rates due to AEs were 26.0% with KdD and 22.2% with Kd. Exposure-adjusted AE rates per 100 patient years were: 171.2 and 151.9 for grade ≥3 AEs and 6.9 and 5.6 for fatal AEs in the KdD and Kd arms, respectively. Updated data by key subgroups will be presented. Conclusion: With approximately 11 months of additional follow-up, a 13.4-month improvement in median PFS was observed in patients treated with KdD (28.6 months) versus patients treated with Kd (15.2 months;HR, 0.59 [95% CI, 0.45-0.78]). Safety was consistent with previously reported results. KdD continues to show a favorable benefit-risk profile and represents an efficacious treatment option for patients with RRMM. [Formula presented] Disclosures: Dimopoulos: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau;BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau;Celgene: Consultancy, Ho oraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau. Quach: GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Consultancy;Amgen, Celgene, karyopharm, GSK, Janssen Cilag, Sanofi.: Membership on an entity's Board of Directors or advisory committees;Amgen, sanofi, celgene, Karyopharm, GSK: Research Funding;GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Honoraria. Mateos: EDOMundipharma: Consultancy;Adaptive: Consultancy;Pharmamar: Consultancy;GlaxoSmithKline: Consultancy;AbbVie: Consultancy;Takeda: Consultancy;Amgen: Consultancy;Celgene: Consultancy;Janssen: Consultancy. Landgren: Pfizer: Consultancy, Honoraria;Merck: Other;Cellectis: Consultancy, Honoraria;Juno: Consultancy, Honoraria;Glenmark: Consultancy, Honoraria, Research Funding;BMS: Consultancy, Honoraria;Binding Site: Consultancy, Honoraria;Celgene: Consultancy, Honoraria, Research Funding;Pfizer: Consultancy, Honoraria;Karyopharma: Research Funding;Merck: Other;Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding;Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding;Glenmark: Consultancy, Honoraria, Research Funding;Juno: Consultancy, Honoraria;Seattle Genetics: Research Funding;Cellectis: Consultancy, Honoraria;Seattle Genetics: Research Funding;Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding;BMS: Consultancy, Honoraria;Adaptive: Consultancy, Honoraria;Amgen: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;Binding Site: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding;Karyopharma: Research Funding. Leleu: Incyte: Honoraria;Merck: Honoraria;Novartis: Honoraria;Amgen: Honoraria;GSK: Honoraria;Sanofi: Honoraria;BMS-celgene: Honoraria;Janssen: Honoraria;Oncopeptide: Honoraria;AbbVie: Honoraria;Carsgen: Honoraria;Karyopharm: Honoraria. Siegel: Janssen: Consultancy, Honoraria, Speakers Bureau;Merck: Consultancy, Honoraria, Speakers Bureau;Amgen: Consultancy, Honoraria, Speakers Bureau;Celulatiry: Consultancy;Karyopharma: Consultancy, Honoraria;Takeda: Consultancy, Honoraria, Speakers Bureau;BMS: Consultancy, Honoraria, Speakers Bureau. Weisel: Takeda: Consultancy, Honoraria;Amgen: Consultancy, Honoraria, Research Funding;Karyopharm: Consultancy, Honoraria;Adaptive: Consultancy, Honoraria;Bristol-Myers Squibb: Consultancy, Honoraria;GlaxoSmithKline: Honoraria;Sanofi: Consultancy, Honoraria, Research Funding;Janssen: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;Abbvie: Consultancy, Honoraria;Roche: Consultancy, Honoraria. Gavriatopoulou: Takeda: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Genesis Pharma: Consultancy, Honoraria;Karyopharm: Consultancy, Honoraria;Amgen: Consultancy, Honoraria. Oriol: Janssen: Consultancy;Celgene: Consultancy, Speakers Bureau;Amgen: Consultancy, Speakers Bureau. Rabin: Janssen, BMS/Celgene, Takeda, Karyopharm, Amgen: Consultancy;Janssen, BMS/Celgene, Takeda: Other: Travel;Jansse, BMS/Celgene, Takeda: Speakers Bureau. Nooka: GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding;Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding;Spectrum Pharmaceuticals: Consultancy;Celgene: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding;Oncopeptides: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Research Funding;Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding;Sanofi: Consultancy, Honoraria;Adaptive Technologies: Consultancy, Honoraria;Takeda: Consultancy, Honoraria, Research Funding. Ding: Amgen: Current Employment. Zahlten-Kumeli: Amgen: Current Employment, Current equity holder in publicly-traded compan . Usmani: Celgene: Other;GSK: Consultancy, Research Funding;Pharmacyclics: Research Funding;Array Biopharma: Research Funding;Seattle Genetics: Consultancy, Research Funding;Merck: Consultancy, Research Funding;Incyte: Research Funding;SkylineDX: Consultancy, Research Funding;Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding;Sanofi: Consultancy, Honoraria, Research Funding;Abbvie: Consultancy;BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding;Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding;Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding.

Radiological management and follow-up of post-COVID-19 patients

Most of the patients who overcome the SARS-COV-2 infection do not present complications and do not require a specific follow-up, but a significant proportion (especially those with moderate/severe clinical forms of the disease) require clinicalradiological follow-up. Although there are hardly any references or clinical guidelines regarding the long-term follow-up of post-COVID-19 patients, radiological exams are being performed and monographic surveillance consultations are being set up in most of the hospitals to meet their needs. The purpose of this work is to share our experience in the management of the post-COVID-19 patient in two institutions thathave had a high incidence of COVID-19 and to propose general follow-uprecommendations from a clinical and radiological perspective. Resumen La mayor parte de los pacientes que superan la infección por SARS-COV-2 no presentan complicaciones ni requieren un seguimiento específico, pero una proporción significativa (especialmente aquellos con formas clínicas moderadas/graves de la enfermedad) necesitan un seguimiento clínico-radiológico. Aunque apenas existen referencias o guías clínicas sobre el seguimiento a largo plazo de estos pacientes post-COVID-19, se están realizando pruebas radiológicas y constituyendo consultas monográficas de vigilancia en la mayor parte de los centros hospitalarios para atender sus necesidades. El propósito de este trabajo es compartir nuestra experiencia en el manejo del paciente post-COVID-19 en dos instituciones que han tenido una elevada incidencia de la COVID-19 y proponer unas recomendaciones generales de seguimiento desde una perspectiva clínica y radiológica.

Radiological management and follow-up of post-COVID-19 patients. / Manejo y seguimiento radiológico del paciente post-COVID-19.

Most of the patients who overcome the SARS-CoV-2 infection do not present complications and do not require a specific follow-up, but a significant proportion (especially those with moderate / severe clinical forms of the disease) require clinicalradiological follow-up. Although there are hardly any references or clinical guidelines regarding the long-term follow-up of post-COVID-19 patients, radiological exams are being performed and monographic surveillance consultations are being set up in most of the hospitals to meet their needs. The purpose of this work is to share our experience in the management of the post-COVID-19 patient in two institutions thathave had a high incidence of COVID-19 and to propose general follow-uprecommendations from a clinical and radiological perspective.