Discussion
fibrosis
DISEASE, DISEASES, FIBROSIS
This study investigated a novel non-invasive anti-CD20 imaging technique in patients with IMID-IP to assess the impact of anti-CD20 expression on subsequent rituximab therapy. While rituximab therapy resulted in complete depletion of B cells in all patients, the clinical outcome was still variable. This is the first study in IMID-IP to show that in vivo pulmonary CD20 expression differs significantly between responders and non-responders to rituximab therapy, as depicted by [89Zr]-rituximab PET/CT. The presence of CD20 cells in the lung was predictive of response in our study, and [89Zr]-rituximab PET/CT therefore has the potential to select patients who will benefit from rituximab therapy.Recently, we have shown that anti-CD20 imaging PET can be used to assess the presence of CD20 in ILD in IMIDs [Despite effective complete depletion of B cells 2 weeks after rituximab therapy, 28% of patients did not respond to therapy. In our previous study, we demonstrated that the recovery of “normal” B cells in the blood from the bone marrow was not a predictor of non-response to rituximab treatment [The sites of CD20 accumulation in the lung are mostly diffuse with variable local areas of increased CD20 presence, such as subpleural regions and interstitial regions, but also some areas of fibrosis in agreement with histological findings [The strengths of the study are the use of a robust clinical assessment and consistent treatment regimens. The diagnosis IMID-IP was made by an experienced multidisciplinary team of ILD specialists, a rheumatologist, and a thoracic radiologist. While IMIDs with ILD are heterogeneous diseases, treatment regimens are quite similar, especially in progressive disease. All patients enrolled in the study were refractory to maintenance doses of corticosteroids (prednisone) and immunosuppressants (azathioprine, cyclofosfamide, and/or methotrexate) for at least 6 months according to the study protocol. Within the study group, the treatment regimen was not changed except that rituximab was added. The corticosteroid maintenance dose was increased in 2 patients who did not respond.Our study also has limitations. First, this study involves a relatively small number of patients in a single-center study with no control group. A small number of patients reduce the statistical power to detect small to moderate treatment effects and the ability to conduct credible subgroup analyses. Nevertheless, we found a significant treatment effect, indicating more than small to moderate benefit from treatment with rituximab. Furthermore, randomization to placebo in these vulnerable patients was considered unethical [Another possible limitation of our study relates to the injection [89Zr]-rituximab in relation to prior exposure to therapeutic rituximab. The first 10 patients received therapeutic rituximab first, followed by [89Zr]-rituximab tracer within 4 h of therapeutic rituximab, as per a previously published pre-loading protocol for oncology patients [The source of the radionuclide may also have an impact on outcomes. In a previous study, [68Ga]-pentixafor was used to analyze CXC chemokine receptor 4 (CXCR4) expression in fibrotic tissue [In conclusion, this prospective phase 2 study in IMIDs with progressive life-threatening ILD demonstrates that 72% responded to rituximab treatment suggesting a significant benefit of this off-label rescue treatment option. In addition, we show that a novel radiolabeled anti-CD20 imaging technique might be useful as a non-invasive predictive biomarker. Our data showed a higher pulmonary CD20 presence in responders compared to non-responders when treated with rituximab and therefore warrant further study into this novel imaging technique.