Type: Oral
Session: 654. Multiple Myeloma: Pharmacologic Therapies: Targeting BCMA
Hematology Disease Topics & Pathways:
Research, Clinical trials, Bispecific Antibody Therapy, Clinical Research, Plasma Cell Disorders, Diseases, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Adverse Events
Methods: Eligible pts were aged ≥18 y, had NDMM (per International Myeloma Working Group [IMWG] criteria), received 4-6 cycles of 3- or 4-drug induction that included a proteasome inhibitor and/or an immunomodulatory drug ± an anti-CD38 antibody and a single or tandem ASCT ± consolidation, and achieved a partial response or better per IMWG 2016 response criteria. Three cohorts at different Tec dose frequencies were evaluated: Cohort 1 (Tec-Len) with Tec dosing at 1.5 mg/kg QW for 2 cycles (C), followed by 3 mg/kg Q2W in C3-6, and 3 mg/kg Q4W in C7+; Cohort 2 (Tec-Len) with Tec dosing at 1.5 mg/kg on Days 8 and 15 in C1, followed by 3 mg/kg Q4W in C2+; and Cohort 3 (Tec) dosing at 1.5 mg/kg on Days 8 and 15 in C1, followed by 3 mg/kg Q4W in C2+. All pts received the same inpatient Tec step-up schedule in C1 (0.06 mg/kg; 0.3 mg/kg). Len 10 mg QD in C2-4 (if tolerated, 15 mg thereafter) was given in Tec-Len cohorts. Treatment duration was 2 y for all pts; in Tec-Len cohorts, Tec was stopped after 13 cycles of treatment if complete response or better (≥CR) was achieved. Adverse events (AEs) were graded per Common Terminology Criteria for Adverse Events v5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per American Society for Transplantation and Cellular Therapy guidelines. Investigator-assessed response was based on IMWG 2016 criteria.
Results: Across 3 cohorts, 94 pts were enrolled (Cohort 1, n=32; Cohort 2, n=32; Cohort 3, n=30). At a median follow-up of 14.4, 5.0, and 4.9 mo, 97% of pts in each cohort (n=31, 31, 29, respectively) remained on treatment. Baseline characteristics were generally balanced between cohorts with a median age of 58-59 y. Pts in Cohort 1, 2, and 3 had received a median of 15, 6, and 6 maintenance cycles, respectively.
Neutropenia and infections were the most common Grade 3/4 treatment-emergent AEs (TEAEs). Compared with Cohort 1, the cumulative incidence of any grade and Grade 3/4 neutropenia at 4 mo showed a decreased trend in Cohorts 2 and 3 with less frequent Tec dosing (Cohort 1: any grade/Grade 3/4 incidence, 69%/66%; Cohort 2: 44%/41%; Cohort 3: 37%/28%). A similar trend was observed for all grade infections with less frequent Tec dosing (Cohort 1: 78%; Cohort 2: 63%; Cohort 3: 61%). Among 68/94 (72.3%) pts who had any grade hypogammaglobulinemia, 63/68 (92.6%) received ≥1 dose of IVIg. The overall CRS rate was 43.6%, with 6.4% Grade 2 and no high-grade events. The CRS rate following the first treatment dose of Tec (1.5 mg/kg) was low at 7.4%. No ICANS were reported.
TEAEs led to treatment discontinuations in 2 pts (1 each in Cohorts 2 and 3) and death in 1 pt (Cohort 2; due to COVID-19 during C1, prior to the start of Len).
In Cohort 1, all 28 pts with MRD assessments at 12 mo were in MRD negative CR. Among MRD positive pts at study entry, 10 (100%) converted to MRD negative CR during treatment. Among 16 pts who had <CR at study entry, 100% achieved ≥CR during treatment. At the time of clinical cutoff, no pts had progressed on treatment. Efficacy data from Cohorts 2 and 3 and longer-term outcomes from Cohort 1 will be shared at the meeting.
Conclusions: Overall, Tec-Len and Tec can be safely administered as maintenance therapy following ASCT in NDMM. Cohorts 2 and 3 showed a trend for improved early safety outcomes with less frequent Tec dosing compared with Cohort 1. Tec-Len demonstrated deepening of responses and 100% MRD negative CR rate at 12 mo in Cohort 1 evaluable pts. These data informed the randomized part of MajesTEC-4/EMN30, which is actively enrolling.
Disclosures: Zamagni: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: 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; Janssen: 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; Menarini Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees. Špička: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees; Takeda: 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; Novartis: Membership on an entity's Board of Directors or advisory committees; Charles University and General University Hospital in Prague, Czech republic: Current Employment; BMS: Honoraria; Janssen-Cilag: Honoraria. Tahri: European Myeloma Network: Current Employment; Erasmus Medical Center: Ended employment in the past 24 months; Affiliation with Dana-Farber Cancer Institute, Boston, US: Ended employment in the past 24 months. Nijhof: BMS: Honoraria; Janssen: Honoraria. Terpos: Amgen: Honoraria; BMS: Honoraria; AstraZeneca: Honoraria, Other: travel; EUSA Pharma: Honoraria; GSK: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Menarini/Stemline: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Other: travel; Novartis: Honoraria; Antengene: Honoraria, Research Funding; Swixx: Honoraria; EUSA: Other: travel. Radocha: GSK: Consultancy; Johnson & Johnson: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Mina: GSK: Honoraria; Takeda: Honoraria; BMS: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Johnson & Johnson: Consultancy, Honoraria, Speakers Bureau. Cengiz Seval: Ankara University Faculty of Medicine: Current Employment; Pfizer: Honoraria, Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; BMS: Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding, Speakers Bureau; Cellectar Biosciences: Research Funding; Menarini: Honoraria. Beksac: Janssen: Research Funding, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Sanofi: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; GSK: Research Funding; Menarini: Consultancy, Other: advisory. Rodriguez: Amgen: Consultancy; Takeda: Consultancy; AbbVie: Consultancy; BMS: Consultancy; Johnson and Johnson: Consultancy; Sanofi: Consultancy; Janssen: Consultancy; Karyopharm Therapeutics: Consultancy. Pasquini: Novartis: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Delforge: GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS: Consultancy, Honoraria; University Hospital Leuven: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Amgen, BMS, GSJ, Janssen, Sanofi, Pfizer, F. Hoffmann-La Roche Ltd: Consultancy; Amgen, BMS, GSJ, Janssen, Sanofi, Pfizer, Roche: Honoraria. Hungria: Pfizer and Regeneron: Honoraria, Speakers Bureau; Johnson & Johnson: Honoraria; Bristol Myers Squibb: 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; GSK: 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; Pfizer: 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; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Reece: Janssen, BMS, Sanofi, ORIC, Princess Margaret Cancer Centre: Other: Grants; BMS: Membership on an entity's Board of Directors or advisory committees; BMS, Janssen, Takeda, Pfizer: Honoraria; BMS, Janssen, Sanofi, GSK, Pfizer: Consultancy. Moreau: Celgene, Janssen, Takeda, Amgen, Pfizer, AbbVie, Sanofi: Other: Participation on a Data Safety Monitoring Board or advisory board ; Celgene, Janssen, Takeda, Amgen, Pfizer, AbbVie, Sanofi: Honoraria; Celgene, Janssen, Takeda, Amgen, Pfizer, AbbVie, Sanofi: Consultancy. Cohen: Amgen: 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, Research Funding; Amgen, BMS, GSK, JNJ, Medison, Pfizer, Roche, Sanofi Aventis, Takeda: Consultancy; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Johnson and Johnson: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Kim: Janssen: Research Funding; Sanofi: Research Funding; Amgen: Research Funding; BMS: Research Funding. Dytfeld: Janssen, Gilead, Amgen: Consultancy, Honoraria; Janssen, Amgen: Research Funding. Minařík: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: 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. Strassl: Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Stemline: Consultancy, Honoraria; Janssen: Consultancy, Research Funding; GSK: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Schreder: Janssen: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Abbvie: Consultancy. Krawczyk: University of Galway: Current Employment; Health Research Board, Ireland: Research Funding. Schjesvold: Targovax: Research Funding; Pfizer: Other: Honoraria for lectures and educational material; SkylineDx: Other: Honoraria for lectures and educational material; GSK: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Other: Honoraria for lectures and educational material, Research Funding; Daiichi Sankyo: Other: Honoraria for lectures and educational material; Oncopeptides: Consultancy, Other: Honoraria for lectures and educational material, Research Funding; AbbVie: Consultancy, Other: Honoraria for lectures and educational material; Bristol Myers Squibb: Consultancy, Other: Honoraria for lectures and educational material; Amgen: Other: Honoraria for lectures and educational material; Takeda: Consultancy, Other: Honoraria for lectures and educational material; Sanofi: Consultancy, Other: Honoraria for lectures and educational material, Research Funding; Schain: Other: Honoraria for lectures and educational material; Skylite: Other: Honoraria for lectures and educational material; Celgene: Consultancy, Other: Honoraria for lectures and educational material, Research Funding; Novartis: Other: Honoraria for lectures and educational material; GlaxoSmithKline: Consultancy, Honoraria, Research Funding. Cook: Roche: Consultancy; Pfizer: Consultancy, Speakers Bureau; BMS/Celgene: Research Funding; Menorini Stemline: Consultancy; Takeda: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau. Gyula Szabo: GSK: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen-Cilag: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Sanofi: Consultancy. Hájek: Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; BMS: Consultancy, Honoraria, Research Funding; PharmaMar: Consultancy, Honoraria; Novartis: Consultancy, Research Funding. Raab: Heidelberg University Hospital Medical Clinic V, Multiple Myeloma: Current Employment; BMS, AMGEN, GSK, Janssen, SANOFI, PFIZER, AbbVie, Oncopeptides, Takeda: Consultancy; BMS, Janssen, Heidelberg Pharma: Research Funding; BMS, AMGEN, GSK, Janssen, SANOFI, PFIZER, AbbVie, Oncopeptides: Honoraria; Janssen, AMGEN, BMS, Sanofi, AbbVie, GSK: Membership on an entity's Board of Directors or advisory committees; BMS, AMGEN, Janssen, Sanofi, AbbVie, Oncopeptides: Other: Travel. Mangiacavalli: Menarini Stem Line: 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; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; IRCCS Fondazione Policlinico San Matteo, Pavia: Current Employment; BMS: Consultancy, Honoraria. Einsele: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene/Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria; BMS: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Spencer: F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Research Funding. Boccadoro: Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Research Funding. Vassalou: Health Data Experts: Consultancy, Current Employment, Ended employment in the past 24 months. Pei: Janssen Research & Development, LLC: Current Employment, Current equity holder in publicly-traded company. Shi: Janssen Research & Development, LLC: Current Employment, Current equity holder in publicly-traded company. Krevvata: Janssen: Current Employment, Current holder of stock options in a privately-held company. Gruber: Janssen: Current Employment, Current equity holder in publicly-traded company. Sakabedoyan: Janssen: Current Employment, Current holder of stock options in a privately-held company. Cobb: Janssen: Current Employment, Current equity holder in publicly-traded company. Jasielec: Johnson and Johnson: Current Employment, Current holder of stock options in a privately-held company. Amin: Janssen: Current Employment, Current equity holder in publicly-traded company. Kobos: Johnson & Johnson: Current Employment, Current holder of stock options in a privately-held company. Sonneveld: Oncopeptides: Patents & Royalties; European Myeloma Network: Other: President; Pfizer: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding. van de Donk: Servier: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees.
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