ABSTRACT
Background: Secondary antibody deficiency (SAD) is typical of hematological malignancies, such as chronic lymphocytic leukemia (CLL), multiple myeloma, and lymphoma or as a side effect of their treatment. Immunological defects are observed in 25-85% of CLL patients (pts), both naïve and previously treated, depending on duration, stage of disease, treatment, patient's age, and comorbidities. (Na et al., 2019;Patel et al., 2019;Zinzani et al., 2019;Reiser et al., 2017). In CLL pts, SAD increases the risk of infections, with overall higher morbidity and mortality Antibiotics administration and vaccinations are recommended as risk-reduction strategies. No real guidelines are available, but many indications warrant immunoglobulins replacement therapy (IgRT) in selected pts with low IgG (<5 g/l) or with more than three infective episodes per year despite antibiotic treatment and timely vaccination (Na et al., 2019;Reiser et al., 2017). No clear indications are available regarding the delivery method (intravenous or subcutaneous), dosage, frequency of administration, and duration of IgRT. Aims: The aim of this study is to assess the efficacy and the safety of SCIg on CLL patients in terms of infectious events, immune recovery and lymphocytes subset, impact on quality of life (QoL) on CLL pts in the Covid-19 era. Methods: Ten CLL pts with SAD have been treated with subcutaneous IgRT (SCIg) from October 2019 to December 2020. The median age and body weight of the pts were 66 years (56-88) and 68 kg (52-86) respectively. Five patients had comorbidities (hypertension, diabetes mellitus, and lung diseases) and 90% of them had an Eastern Cooperative Oncology Group (ECOG) performance 0-1. Five pts presented with unmutated IgVH and one of them also had 17p deletion. The median number of prior therapies was 2 (IBR, BR, Chl-antiCD20, FCR, in 5, 4, 4, 3 pts, respectively). At that time, 7 pts were on therapy (IBR, Ven, Alkylating Agent in 4, 1, 2 pts, respectively). None presented neutropenia. All pts underwent antibiotic prophylaxis with trimetroprin-cotimoxazole, sometimes associated with clarithromycin, and influenza vaccinations. The median baseline IgG level was 485mg/dl (118-817), with a median of 3 infection/year (1-5;pneumonia, UTI). Patients' characteristics are reported in Table 1. All pts received 10 g total dose hyaluronidase-free SCIg over a 1 h in double-needle subcutaneous infusion every 15 days for one year, independently from body weight. After the first dose, administered in a hospital setting to make the patient comfortable with their personal pump, the next doses were self-administered at home. The IgG level and CD4/CD8, CD19, and CD16/56 (natural killer, NK) lymphocytes subset were recorded at baseline and every three months during the observation period to monitor the immunological reconstitution as the therapy went on. Results: In our monocentric experience from October 2019 to December 2020 no patient experienced infectious events nor Covid-19 mediated interstitial pneumonia while on SCIg therapy. All patients tolerated well the therapy: nobody interrupted the treatment and only one patient presented a skin rash (grade 2). Both dosage and administration schedule have been stable over time. Dealing with humoral immunity, IgG levels arose from a median of 485 (118-817) mg/dl to a stable median value >600 mg/dl from 6 months onward. As expected, IgA and IgM values remained below normal levels. Dealing with cellular immunity, T-cells including CD4, CD8, and natural killer (NK, CD16/56) cells displayed a stable fashion until 6 months. On the other hand, the CD19 B cells values reflect both the disease status and the ongoing treatment effects. Results are reported in Table 1. Finally, we observed advantages on adherence to treatment, QoL, and costs, since pts did not need to go to the hospital with the help of a care-giver, rather they could comfortably get their SCIg at home without any assistance. Conclusion: SCIg administration in CLL pts with SAD is efficacious and safe as infectious prophylaxis, with hig er median IgG levels, thanks to both pharmacokinetic advantages and improved adherence to treatment. Especially in the Covid-19 era, the subcutaneous route is preferred to the intravenous one, because of the self-administration at home and the granted availability to the drug itself. Finally, subcutaneous administration gives advantages to the QoL and hospital expenditure.
ABSTRACT
Background: Secondary antibody deficiency (SAD) is a typical manifestation of haematological malignancies such as chronic lymphocytic leukaemia (CLL), or a side effect of their treatment. Immunological defects are observed in 25-85% of CLL patients (pts) and increases the risk of infections, with overall higher morbidity and mortality. Antibiotics administration and vaccinations are recommended as risk-reduction strategies in those pts. No real guidelines are available to recommend eligibility for prophylaxis, but many indications warrant immunoglobulins replacement therapy (IgRT) in selected pts with low IgG (<5g/l) or with more than 3 infective episodes per year despite antibiotic treatment and timely vaccination. No clear indications are available regarding the delivery method (intravenous or subcutaneous), dosage, frequency of administration and duration of IgRT. Aims: The aim of this study is to assess the efficacy and safety of subcutaneous IgRT (SCIg) and its impact on quality of life (QoL) on CLL pts in Covid-19 era. Methods: Ten CLL pts, have been treated with SCIg from October 2019 to December 2020. Median age and body weight were 66 years (56-88) and 68 Kg (52-86). Comorbidities were present in 5 pts (hypertension, diabetes mellitus, lung diseases). 5 pts had unmutated IgVH and 1 had 17p deletion. The median number of prior therapies was 2 (IBR, BR, Chl-antiCD20, FCR, in 5, 4, 4, 3 pts respectively). At that time, 7 pts were on therapy (IBR, Ven, Alkylating Agent in 4, 1, 2 pts respectively). None presented neutropenia. All pts underwent antibiotic prophylaxis with trimetroprin-cotimoxazole, sometimes associated with clarithromycin, and influenza vaccinations. Median baseline IgG level was 485 mg/dl (118-817), with a media of 3 infection/year (1-5;pneumonia, UTI). All pts received 10 g total dose hyaluronidase-free SCIg over a 1h double-needle subcutaneous infusion every 15 days over one year, independently from their body weight. After the first dose, administered in a hospital setting to make the patient comfortable with their personal pump, the next doses were self-administered at home. The IgG level and CD4/CD8, CD19 and CD16/56 (natural killer, NK) lymphocytes subset were recorded both at baseline and during the observation period to monitor the immunological reconstitution as the therapy went on. Results: No patient experienced infectious events during the SCIg therapy nor Covid-19 mediated interstitial pneumonia. All patients tolerated the therapy: nobody interrupted the treatment and only one patient presented a skin rash (grade 2). Both dosage and administration schedule have been stable over time. Dealing with humoral immunity, IgG levels arose from a median of 485 mg/dl (118-817) to a stable median value >600 mg/dl from 6 months onward. About cellular immunity, T-cells including CD4 and CD8 and NK cells displayed a stable fashion until 6 months. On the other hand, the CD19 B cells values reflect both the disease status and the ongoing treatment effects. Results were in Table 1. Finally we observed advantages on both QoL and costs, since pts did not need to go to the hospital with the help of a care-giver, rather they could comfortably get their SCIg at home without any assistance. Summary/Conclusion: SCIg administration in CLL pts is safe and efficacious as infectious prophylaxis, with higher median IgG levels, thanks to its pharmacokinetic advantages and improved adherence to treatment. Especially in the Covid-19 era, the subcutaneous route is preferred to the intravenous one, because of the self-administration at home and the granted availability to the drug itself.