Evaluation whether treatment with the bispecific T-cell engager Teclistamab is effective and safe in therapy-refractory patients with IgM paraproteinemic neuropathies.

Chronic immune-mediated peripheral nervemyelinopathies (CIPNM) caused by IgM paraproteins or anti-myelin-associated glycoproteins (MAG) are progressive and debilitating diseases that may be refractory to current therapies. New therapies based on the recruitment of endogenous T cells are currently tested in autoimmune diseases. However, autologous CAR-T cell therapy is complex and associated with side effects. Efficient “off-the-shelf” therapies with similar efficacy, lower costs, and reduced side effects are urgently needed. The recombinant bispecific T cell engager (BiTE) teclistamab binds to the B cell maturation antigen (BCMA) and the T cell antigen CD3.

Monocentric, prospective case series. Following a positive ethics vote and consent to therapy as part of individual treatment attempts, two patients with treatment-resistant CIPNM received four subcutaneous injections of teclistamab (two step-up doses [0.06 mg/kg and 0.3 mg/kg], 2 maintenance doses [1.5 mg/kg]). Patient 1 (65-year-old woman) suffered from IgM kappa-associated CIPNM. Patient 2 (74-year-old woman) had anti-(MAG) antibody-mediated CIPNM. Outcome parameters included neuropathy-related clinical parameters (maximum walking distance, hand grip strength, and neuropathy scores), electroneurography, nerve ultrasound, and laboratory analyses.

Both patients showed rapid improvement upon treatment: The walking distance increased substantially (baseline: 300 meters; month 6: 2970 meters; baseline125 meters; month 3: 450 meters, respectively) accompanied by reduced nerve swelling and markedly improved electroneurography. Furthermore, some nerves without stimulus response at baseline were detectable during follow-up. IgM kappa paraprotein and high-titer MAG antibodies were undetectable 6 weeks after the first dose of teclistamab, respectively. Overall, treatment with teclistamab was well tolerated.

This findings demonstrate the therapeutic potential of teclistamab in treatment-resistant CIPNM. BiTE therapy was well tolerated, effective, and should be investigated in other neuroimmunological diseases and in clinical trials.