ABSTRACT Introduction: COVID-19 can lead to a hyper-inflammatory state. CD6 is a glycoprotein expressed on mature T-lymphocytes, which is a crucial regulator of the T-cell activation. Itolizumab is an antibody targeting CD6. Clinical data in autoimmune diseases indicate that it lowers multiple cytokines primarily involving the Th1/Th17 pathway. Objective: to preliminarily assess the safety and impact of itolizumab on interleukin-6, pulmonary function and mortality of COVID-19 patients. Methods: Sixty-eight moderate, severe and critical patients were included in an expanded-access trial in Cuba. Itolizumab was administered together with other therapies included in the national protocol for SARS-CoV-2. Results: All patients completed the first infusion and 41 received 2 doses. Median age was 68 and 94 % have comorbidities. Itolizumab improved the lung function and was well tolerated; 3 subjects had related serious adverse events. Interleukin-6 decreased in individuals with high levels and did not change in those with lower concentration. 14-day lethality rate was 4 % and 18 % for moderate and severe patients. Although this was not a randomized study, preliminary data suggest that itolizumab reduced the death probability in comparison to controls. Time to treatment, neurological manifestations, biomarkers like NLR, neutrophil count and interleukin-6 were significantly associated with higher lethality. Conclusions. Itolizumab can disrupt the inflammatory cascade and might prevent the COVID-19 associated morbidity and mortality.

RESUMEN Introducción: La neumonía COVID-19 puede conducir a un estado hiperinflamatorio. El CD6 es una glicoproteína expresada en linfocitos T maduros que constituye un regulador crucial de la activación de las células T. El itolizumab es un anticuerpo monoclonal que reconoce el CD6. Los datos clínicos en enfermedades autoinmunes indican que reduce múltiples citocinas proinflamatorias. Objetivo: evaluar la seguridad y el impacto de itolizumab sobre la interleucina-6, la función pulmonar y la mortalidad de los pacientes con COVID-19. Métodos: Se incluyeron 68 pacientes moderados, severos y críticos en un ensayo de acceso expandido en Cuba. El itolizumab se administró junto con otras terapias incluidas en el protocolo nacional para el SARS-CoV-2. Resultados: Todos los pacientes completaron la primera infusión y 41, recibieron 2 dosis. La mediana de edad fue de 68 años y el 94 % era portador de comorbilidades. El itolizumab mejoró la función pulmonar y fue bien tolerado; 3 sujetos tuvieron eventos adversos graves relacionados. La interleucina-6 disminuyó en individuos con niveles altos y no se incrementó en aquellos pacientes con concentraciones más bajas. La tasa de letalidad a los 14 días fue del 4 % y del 18 % para los pacientes moderados y graves. Aunque este estudio no fue aleatorizado, los datos preliminares sugieren que itolizumab redujo la probabilidad de muerte en comparación con los controles. El tiempo de tratamiento, las manifestaciones neurológicas y los biomarcadores como la razón entre neutrófilos y linfocitos, recuento de neutrófilos y la interleucina-6 se asociaron significativamente con mayor letalidad. Conclusiones. El itolizumab puede interrumpir la cascada inflamatoria y prevenir la morbilidad y mortalidad asociada al COVID-19.

Abstract INTRODUCTION Racotumomab is a therapeutic vaccine based on a monoclonal anti-idiotypic antibody developed by the Molecular Immunology Center in Havana, Cuba, that is registered in Cuba and Argentina for treatment of non-small cell lung cancer. It induces a specific humoral and cellular immuneresponse against the N-glycolyl GM3 (NeuGcGM3) ganglioside present in tumor cells, thereby provoking the death of these cells. OBJECTIVE Evaluate racotumomab vaccine use as switch maintenance and second-line therapy for patients with inoperable non-small cell lung cancer in routine clinical practice, outside the framework of clinical studies, and assess the overall survival, stage-specific survival and safety in these patients. METHODS A descriptive, retrospective study was carried out in patients diagnosed with non-small cell lung cancer not suitable for surgical treatment, who received racotumomab as a part of switch maintenance or second-line treatments. Overall survival was defined from diagnosis and from the first immunization, until death. RESULTS We included 71 patients treated with racotumomab, 57.7% (41/71) of whom were in stages IIIB and IV of non-small cell lung cancer. Of the patients, 84.5% (60/71) had no adverse events, and 15.5% (11/71) had mild adverse reactions. The median overall survival was 24.5 months, calculated from the first immunization, 17.2 months for those who received racotumomab as switch maintenance and 6.8 months for patients who had progressed after the first line of treatment. CONCLUSIONS Racotumomab in routine clinical practice prolonged overall survival in patients with non-small cell lung cancer treated in switch maintenance, and in stage IV patients who received the treatment as second-line therapy. The vaccine was well tolerated.