Type: Oral
Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Bispecific Monoclonal Antibodies in Myeloma
Hematology Disease Topics & Pathways:
Biological therapies, Research, Translational Research, Plasma Cell Disorders, Diseases, Therapies, Lymphoid Malignancies
Methods. Patients were eligible for tec-dara-len if they had received 1–3 prior lines of therapy (LOT), including a proteasome inhibitor and immunomodulatory drug. In this cohort, patients received weekly doses of tec (0.72 or 1.5 mg/kg with step-up dosing) plus the approved schedules of dara 1800 mg + len 25 mg. Responses were investigator assessed per International Myeloma Working Group criteria and adverse events (AEs) by CTCAE v5.0, except for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which were graded per ASTCT guidelines.
Results: 32 patients received tec-dara-len (0.72 mg/kg, n=13; 1.5 mg/kg, n=19). At the data cutoff (July 11, 2022), median follow-up was 5.78 months (mo; range, 1.0–10.4) and median treatment duration was 4.98 mo (range, 0.10–10.35). Median age was 62 years (range, 38–75); 87.5% were male. All patients had received prior MM treatment; median prior LOT was 2 (range, 1–3), and 31.3% were anti-CD38 exposed. The most frequent AE was CRS (81.3% [n=26]). All CRS events were grade 1/2, and 95% of the events occurred during cycle 1 treatment doses. Median time to onset was 2 days (range, 1–8) and median duration was 2 days (range, 1–22). No ICANS events were reported. Other frequent AEs (≥25.0% across both dose levels) were neutropenia (75.0% [n=24]; grade 3/4: 68.8% [n=22]), fatigue (43.8% [n=14]; grade 3/4: 6.3% [n=2]), diarrhea (37.5% [n=12]; all grade 1/2), insomnia (31.3% [n=10]; grade 3/4: 3.1% [n=1]), cough (28.1% [n=9]; all grade 1/2), hypophosphatemia (25.0% [n=8]; all grade 1/2), and pyrexia (25% [n=8]; grade 3/4: 6.3% [n=2]). The frequency of febrile neutropenia was 12.5% (n=4). Infections occurred in 24 patients (75.0%; grade 3/4: 28.1% [n=9]). The most common infections were upper respiratory infection (21.9% [n=7]), COVID-19 (21.9% [n=7]), and pneumonia (21.9% [n=7]). Three patients (9.4%) had COVID-19 pneumonia. One patient (3.1%) discontinued due to an AE (COVID-19) considered unrelated to study drugs; this patient died due to COVID-19. The overall response rate (ORR) was 13/13 evaluable patients (median follow-up, 8.61 mo) at 0.72 mg/kg and 13/16 evaluable patients (median follow-up was less mature at 4.17 mo) at 1.5 mg/kg. Very good partial response or better was achieved in 12 patients at the 0.72 mg/kg dose and was not mature for the 1.5 mg/kg group. Median time to first response was 1.0 mo (range, 0.7–2.0). Preliminary pharmacokinetic concentrations of tec in combination with dara-len were similar to those seen with tec monotherapy. Tec-dara-len treatment led to proinflammatory cytokine production (induction of interleukin-6, soluble interleukin-2Rα, interferon-γ, and tumor necrosis factor-α) and T-cell activation (upregulation of programmed cell death protein-1 and CD38 on peripheral T cells).
Conclusions: Tec-dara-len was well tolerated, with a safety profile consistent with tec or dara-len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of tec. These data warrant further investigation. The randomized phase 3 MajesTEC-7 study will compare tec-dara-len vs the combination of dara, len, and dexamethasone in patients with NDMM ineligible or not intended for autologous stem cell transplant as initial treatment.
Disclosures: Searle: Abbvie: Honoraria; Janssen: Honoraria; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees. Quach: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: receipt of free drug for investigator-initiated study, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: receipt of free drug for investigator-initiated study, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Research Funding; Antengene: 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, Other: leadership or fiduciary role, receipt of free drug for investigator-initiated study , Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: leadership or fiduciary role , Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: leadership or fiduciary role, receipt of free drug for investigator-initiated study , Research Funding. Wong: Catalent Biologics: Consultancy; Genentech: Research Funding; Caelum: Research Funding; Bristol Myers Squibb: Research Funding; Janssen: Research Funding; GSK: Research Funding; Fortis: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Dren Bioscience: Consultancy; Patient Discovery: Research Funding. Megala Costa: Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria; AbbVie: Research Funding; Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Genentech: Research Funding. Hulin: Amgen: Honoraria; BMS: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Takeda: Honoraria; GSK: Honoraria. Janowski: Janssen-Cilag Amgen Astra-Zeneca: Consultancy, Honoraria. Berdeja: Novartis: Research Funding; Incyte: Research Funding; GlaxoSmithKline: Research Funding; Lilly: Research Funding; Genentech: Research Funding; Celgene: Consultancy, Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; Legend Biotech: Consultancy; Fate Therapeutics: Research Funding; EMD Sorono: Research Funding; Ichnos Sciences: Research Funding; CARsgen: Research Funding; Kite Pharma: Consultancy; SecuraBio: Consultancy; Takeda: Consultancy, Research Funding; Acetylon: Research Funding; Amgen: Research Funding; Poseida: Research Funding; C4 Therapeutics: Research Funding; Karyopharm: Research Funding; Janssen: Consultancy, Research Funding; AbbVie: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Cartesian Therapeutics: Research Funding; Celularity: Research Funding; 2Seventy bio: Research Funding; Zentalis: Research Funding; Teva: Research Funding; Bluebird bio: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding. Matous: BeiGene: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees. Husnik: Johnson & Johnson/ Janssen Pharmaceutical: Current Employment. Niu: Janssen: Current Employment. Larsen: Employee of Janssen Pharmaceuticals.: Current Employment. Chen: Janssen: Current Employment. Goldberg: Janssen: Current Employment, Current equity holder in private company. Popat: Takeda: Research Funding; Janssen, Takeda, Celgene, and GSK: Honoraria; Janssen, Takeda, GSK: Other: Travel expenses from Janssen, Takeda, GSK; Janssen: Honoraria; GSK: Honoraria, Research Funding; Roche: Honoraria; BMS: Honoraria; Takeda, AbbVie, GlaxoSmithKline, and Celgene: Consultancy. Spencer: Amgen: Consultancy, Honoraria; Haemalogix: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria.
OffLabel Disclosure: at the time of abstract submission, teclistamab is being investigated for the treatment of multiple myeloma but is not yet not approved