Prospective Assessment of Motor Neurotoxicity and Sarcopenia in CD30+ Lymphoma Patients Treated with Brentuximab Vedotin. Single Center Multidisciplinary Unit Experience

Introduction: Brentuximab Vedotin (BV), a CD30-targeting antibody-drug conjugate, has been increasingly used for the treatment of several CD30+ lymphomas, being BV-induced motor peripheral neurotoxicity (BVIMN) one of the greatest concerns for treating physicians. Patients may develop weakness with hand and foot paresis as most severe manifestation. Risk factors associated with BVIMN are scarcely known. Before treatment, severe muscle mass depletion (sarcopenia) has been associated with increased chemotherapy-related toxicity in several cancer types. To date, the association between BVIMN and sarcopenia is unknown.

Aim: to assess in a multidisciplinary approach the BVIN development in CD30+ lymphoma patients treated at our institution and try to identify those risk factors associated with motor BVIMN development.

Material and Methods: Since January 2019, adult patients from our institution receiving BV are prospectively evaluated in a multidisciplinary unit including hematologists, neurologists and nutritionists. Patients are assessed periodically before, during and after completion of treatment. Neurological assessment includes the clinical version of the Total Neuropathy Score (TNSc©), including muscle strength, NCI.CTC gradation scale, patient reported outcomes (PROMs), handgrip dynamometry and conventional nerve conduction studies (NCS) at upper and lower extremities. Nutritional assessment includes anthropometry, laboratory parameters, and body composition analysis of the cross-sectional CT o CT-PET scan at the level of the 3rd lumbar vertebra (L3). Skeletal muscle index (SMI), reflecting muscle mass, and skeletal muscle density (SMD), associated with muscle strength, are used to determine sarcopenia. The association between sarcopenia and BVIMN are evaluated.

Results: A total of 58 patients were included in the analysis, of which, 62% had Hodgkin lymphoma and 38% had CD30+ T cell lymphomas, including 8 patients with Mycosis Fungoides. The median age at BV-based treatment initiation was 45 years [21-92], with a predominance of men (55.2%). ECOG was 0,1,2 in 59.6%, 29.8% and 10.6% of patients. In 24% and 76% of patients, BV was administered in monotherapy or in combination with chemotherapy, respectively. The mean total dose of BV received was 856.85 +/- 170 mg. At baseline, 45.2% of patients had sarcopenia. Serum albumin was 42 g/L [28-50]. No differences in cumulated received BV dose between patients with or without sarcopenia were identified. At finishing chemotherapy, BVIN was developed in 72.2% patients, mostly of mild severity (66.7%). Rates of sensory BVIN were: 44.4% grade 1, 22.4% grade 2 and 3.7% grade 3. Motor BVIN was observed in one third (27.8%) of patients: 7.4% (grade 1), 14.8% (grade 2) and 5.6% (grade 3). Patients with moderate (> grade 2) motor BVIN were younger (37 vs 59 years old, p=0.04). Baseline sarcopenia was more frequent in the group of patients developing moderate BVIMN (35% vs 6%, p=0.06). No association with baseline demographic, anthropometric characteristics, or handgrip results were identified. Motor neurotoxicity correlated significatively with motor NCS impairment in upper (r= -0.472, p=0.023) and lower (r=-0.331, p=0.07) extremities.

Conclusions: Motor neurotoxicity may develop in one third of patients receiving BV alone or in combination. Sarcopenia, which is common (45.2%) in BV candidates, could be associated with a higher risk of developing motor BVIN. Motor severity of BVIN can be objectively assessed with neurophysiological tests.