Teclistamab in relapsed/refractory systemic AL amyloidosis.

Abstract

7562 Background: Systemic light chain amyloidosis (AL) is clonal plasma cell disorder characterized by the deposition of fibrils derived from immunoglobulin light chains. Treatment paradigms have been based on therapies for multiple myeloma. Teclistamab is a bispecific antibody approved for use in relapsed refractory multiple myeloma. We report on its impact in patients with AL. Methods: We analyzed data on hematologic and organ responses and treatment-related side effects in patients receiving Teclistamab for relapsed refractory AL. Mayo systems were used to characterize the disease stages. Adverse events were graded with the NCI CTCAE v5.0; CRS was graded according to ASTCT criteria. Results: Eight patients were identified (Table 1). All had relapsed refractory disease. Six had AL-λ and 2 AL-κ type. Five had cardiac involvement, 3 with stage III and 2 with stage II. Median prior lines of therapy was 4 (3-10). All were previously treated with Daratumumab and 5/8 had previously undergone autologous stem cell transplant. Median bone marrow plasmacytosis was 8.5% and median involved free light chain (iFLC) was 64.3mg/L (23.1 - 331). CD138-selected marrow findings included t(11;14), gain 1q and del 17p, each in 2 patients. Patients received escalating doses of Teclistamab. Two patients had grade 3 toxicities; one, a woman in her 80’s, experienced a hepatic aminotransferase spike greater than 1000 the day after receiving the first 0.6mg/kg dose and subsequently after only that dose achieved an unmaintained CR that has continued for over 7 months; the other, a woman in her 70’s, had grade 3 thrombocytopenia that has slowly resolved after Teclistamab was stopped. Two patients experienced grade 1 CRS. The hematologic response rate was 100% with 7 CR and 1 VGPR. The cardiac response rate was 29% (2/7; 1 CR, 1 PR) and the renal response rate was 20% (1/5). No patients have relapsed or died. Conclusions: In patients with relapsed refractory AL Teclistamab showed impressive hematologic activity and manageable side effects. A strong case exists for investigating Teclistamab prospectively in this population. Baseline characteristics and response. Patient iFLC Cytogenetics BM Plasma cells Cardiac stage Renal stage Organs involved Prior lines of therapies Best Hematological response Organ response 1 (78M) 313 (λ) gain 1q, trisomy 9, 15, 19, 21 3-5% 1 1 Tongue Soft Tissue 3 CR Not Evaluable 2 (81F) 23.1 (λ) t(11:14) 12.4% 3a 2 Heart Kidney 4 CR No Response 3 (72F) 59.6 (λ) Low risk 10% 2 1 GI Heart 7 CR Cardiac Response 4 (78M 114 (κ) Normal 3-5% 3a 2 Heart Kidney 10 CR No Response 5 (68) 35.1 (λ) Normal 30-40% 3a 2 Heart Kidney 3 VGPR No Response 6 (65F) 69 (κ) t(11:14), del(17p) 3-5% 3b 2 Peripheral Nervous System Heart Kidney 4 CR No Response 7 (69M) 228 (λ) Normal 7% 3a 1 Heart 4 CR No Response 8 (69f) 42.4 (λ) gain 1q, trisomy 9, del17p 10% 2 2 Heart Kidney 4 CR Renal Response