Tolerability of Bispecific Antibodies in Relapse/Refractory Multiple Myeloma (RRMM) Patients with Severe Renal Insufficiency: Case Series

Multiple Myeloma (MM) is the 2^nd most common hematologic malignancy in the United States. While MM is not curable, novel therapies have significantly increased time to progression, decreasing morbidity and mortality. Teclistamab (Tec) and Talquetamab (Tal), both bispecific antibodies, have been approved for relapsed-refractory Multiple Myeloma (RRMM) (New Engl J Med. 2022; 2232-2244.; New Engl J Med. 2022;495-505.), but patients with creatinine clearance (Crcl) < 40 mL/min were excluded. We present two patients with renal insufficiency who have had positive response to Tec and Tal without excessive toxicity.

Patient 1: 67-year-old man with Kappa light chain MM, had progression of disease (POD) on his 7^th line of therapy. Baseline CrCl was 31 ml/min (Cr 2.92 mg/dl, weight 196 lbs) without need for dialysis. He was started on step-up dosing of Tec June 30, 2023. Tec was given subcutaneously (SC) at usual prescribed dose: D1, 0.06 mg/kg; D4, 0.3 mg/kg; D7, 1.5 mg/kg. This was followed by standard weekly dosing at 1.5 mg/kg. After one year, frequency was reduced to every 2 weeks. Labs at time of progression: white cell count (WBC) 2.78 K/mcl, Hemoglobin (Hgb) 10.1 g/dL, platelets (Plt) 61 K/mcl, Calcium (Ca) 8.6 mg/dL, Albumin (Alb) 3.5 g/dl, 24 urine total protein (TP) 1,141 mg/day with 676.1 mg (59.2%) kappa light chain, Creatinine peaked at 5.10 mg/dL, serum Kappa light chain peaked at 3726 mg/L with Kappa/Lambda (K/L) ratio 240.10 (normal 0.26-1.65). Myeloma bone survey without new lytic lesions. Bone Marrow (BM) biopsy with <1% polyclonal plasma cells. Prophylaxis included antiviral and anti-pneumocystis jirovecii (PJP). He required immunoglobulin (IVIG) replacement to maintain IgG level of at least 400 mg/dl. He did not require granulocyte colony-stimulating factor, blood or platelet transfusion. No dose reductions were needed. Patient did not experience any signs or symptoms of neurotoxicity or cytokine release syndrome (CRS) and had no infections. He responded after 1 cycle of Tec. He has achieved a stringent complete response with normal K/L ratio (0.88), normal 24 hr Urine TP (223 mg/day) with normal immunofixation (IF), BM with no clonal plasma cells and minimal residual disease negative at 10^-6 using next generation sequencing. Creatinine is stable at 3.5 mg/dl with CrCl 23 ml/min.

Patient 2: 75-year-old woman with Lambda light chain MM had POD on her 6^th line of therapy. CrCl was 13.44 ml/min (Cr 2.72 mg/dl, weight 106 lbs), without need for dialysis. She was started on Tal March 27, 2024. Tal was given SC with standard step up dosing: D1, 0.01 mg/kg; D4, 0.06 mg/kg; D7, 0.4 mg/kg; followed by standard weekly dosing of 0.4 mg/kg. After one cycle, frequency was reduced to every 2 weeks due to cytopenia. Labs at time of progression: WBC 6.61 K/mcl, Hgb 9.0 g/dL, Plt 228 K/mcl, Ca 10.7 mg/dL, Alb 3.0 g/dl, 24 Urine TP 405 mg/day with 163.5 mg/day (40.4%) lambda light chain. Creatinine peaked at 5.75 mg/dl, and lambda light chain peaked at 1759 mg/L with K/L ratio 0.00. Myeloma bone survey without new lytic lesions. BM biopsy with 70% Lambda positive plasma cells. Prophylaxis included antiviral and anti-PJP. She required IVIG replacement to maintain IgG level of at least 400 mg/dl. She tolerated step up dosing well and did not experience any signs or symptoms of neurotoxicity or CRS and had no infections. Patient responded after 1 cycle of Tal with a partial response (Lambda 617.71 mg/l). Frequency was changed to biweekly 0.4 mg/kg dosing after 1 cycle due to cytopenia with hgb 7.7 g/dL, plts 16 K/mcL, WBC 1.98 K/mcL, and ANC 1.02 K/mcL. She required one unit each of plts and packed red blood cells. She initially required supportive measures with erythropoietin, Romiplostin and intermittent granulocyte colony-stimulating factor which later was stopped. She does have symptoms of dysgeusia, but has maintained her weight. She has achieved a very good partial response, with normal lambda light chain 6.36 mg/L and normal K/L ratio 0.63. BM biopsy has not yet been done. 24-hour urine TP 203 mg/day with negative immunofixation. Creatinine improved to 1.5 mg/dl with CrCl 24 ml/min.

Teclistamab and Talquetamab seem to be well tolerated in RRMM patients with CrCl < 40ml/min without added toxicities. Both of our 2 patients responded well to treatment. Patients with severe renal insufficiency and RRMM should be considered for such treatments.

Efebera:Oncopeptides, Sanofi, Janssen Oncology, Pfizer: Consultancy; Takeda, Janssen, Akcea Therapeutics, Alnylum: Speakers Bureau; Takeda, Oncopeptides, Alnylam, Sanofi, GlaxoSmithKline, ORCA Therapeutics, Bristol Myers Squibb/Celgene, Pharmacyclics through Alliance and AFT: Research Funding. William:Morphosys: Consultancy; Genmab: Consultancy; BMS: Consultancy; ADC Therapeutics: Consultancy; Guidepoint Global: Consultancy.