Tolerability of Teclistamab and Talquetamab in Relapse/Refractory Multiple Myeloma (RRMM) Patients with Severe Renal Insufficiency: Case Series

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Multiple Myeloma (MM) is the 2nd most common hematologic malignancy in the United States. While MM is not curable, novel therapies have increased time to disease progression. Teclistamab (Tec) and Talquetamab (Tal), both bispecific antibodies, are 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. In an effort to include these patients in standard therapies, we present three patients with renal insufficiency who have responded to Tec and Tal without added toxicity. Patient 1: 67 year old man with Kappa light chain MM, progressed on 8th line of therapy. Baseline CrCl was 31 ml/min. Labs at progression: 24 urine total protein (TP) 1,141 mg/day with 676.1 mg (59.2%) kappa light chain(KFLC), creatinine (Cr) peaked at 5.10 mg/dL, serum KFLC peaked at 3726 mg/L, kappa/lambda (K/L) ratio 240.10, bone Marrow (BM) with <1% polyclonal plasma cells. Started Tec June 30, 2023 at prescribed dose. Did not experience neurotoxicity or cytokine release syndrome (CRS). Achieved a stringent complete response with normal K/L ratio, normal 24 hr Urine TP with normal immunofixation (IF), BM without clonal plasma cells. Cr is stable at 3.5 mg/dl with CrCl 23 ml/min. Patient 2: 75 year old woman with Lambda light chain MM progressed on 7th line of therapy. CrCl was 13.44 ml/min. Labs at progression: 24 Urine TP 405 mg/day with 163.5 mg/day (40.4%) lambda light chain (LFLC). Cr peaked at 5.75 mg/dl, LFLC peaked at 1759 mg/L, BM with 70% Lambda positive plasma cells. Started Tal March 27, 2024 at prescribed dose. After 1 cycle frequency was reduced to every 2 weeks due to cytopenia. Did not experience neurotoxicity or CRS. Reported dysgeusia, but maintained weight. Achieved a very good partial response with normal K/L ratio, normal 24-hour urine TP with negative IF. Cr improved to 1.5 mg/dl with CrCl 24 ml/min. Patient 3: 80 year old woman with IgG Kappa MM progressed on 8th line of therapy. CrCl was 9.0 ml/min. Labs at progression: 24 Urine TP 1605 mg/day with 180 mg/day (11%) IgG kappa. Cr peaked at 3.52 mg/dl, KFLC 40.62 mg/L, k/L ratio 5.83, monoclonal protein 1500 mg/dl, BM with 30% kappa positive plasma cells. Started on Tal July 23, 2024 at prescribed dose followed by biweekly dosing due to age. Dosing changed to monthly with cycle 4 due to side effects. Had grade 2 neurotoxicity and was initiated on IV dexamethasone. Returned to her baseline within 48 hours. Reported dysgeusia, but has maintained weight. She has dermatologic symptoms with skin irritation which has improved with ammonium lactate. Patient has acheived a partial response with monoclonal protein 400 mg/dl. Cr improved to 1.85 mg/dl with CrCl 16.2 ml/min. Tec and Tal seem to be well tolerated in RRMM patients with CrCl < 40ml/min without added toxicities. Patients with severe renal insufficiency and RRMM should be considered for such treatments

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