ABSTRACT
BACKGROUND: Secondary central nervous system lymphoma (SCNSL) confers a dismal prognosis and treatment advances are constrained by the lack of prospective studies and real-world treatment evidence. METHODS: Patients with SCNSL of all entities were included at first diagnosis and patient characteristics, treatment data, and outcomes were prospectively collected in the Secondary CNS Lymphoma Registry (SCNSL-R) (NCT05114330). FINDINGS: 279 patients from 47 institutions were enrolled from 2011 to 2022 and 243 patients (median age: 66 years; range: 23-86) were available for analysis. Of those, 49 (20 %) patients presented with synchronous (cohort I) and 194 (80 %) with metachronous SCNSL (cohort II). The predominant histology was diffuse large B-cell lymphoma (DLBCL, 68 %). Median overall survival (OS) from diagnosis of CNS involvement was 17·2 months (95 % CI 12-27·5), with longer OS in cohort I (60·6 months, 95 % CI 45·5-not estimable (NE)) than cohort II (11·4 months, 95 % CI 7·8-17·7, log-rank test p < 0.0001). Predominant induction regimens included R-CHOP/high-dose MTX (cohort I) and high-dose MTX/cytarabine (cohort II). Rituximab was used in 166 (68 %) of B-cell lymphoma. Undergoing consolidating high-dose therapy and autologous hematopoietic stem cell transplantation (HDT-ASCT) in partial response (PR) or better was associated with longer OS (HR adjusted 0·47 (95 % CI 0·25-0·89), p = 0·0197). INTERPRETATION: This study is the largest prospective cohort of SCNSL patients providing a comprehensive overview of an international real-world treatment landscape and outcomes. Prognosis was better in patients with SCNSL involvement at initial diagnosis (cohort I) and consolidating HDT-ASCT was associated with favorable outcome in patients with PR or better.
Subject(s)
Central Nervous System Neoplasms , Hematopoietic Stem Cell Transplantation , Lymphoma, Large B-Cell, Diffuse , Humans , Aged , Prospective Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Rituximab/therapeutic use , Treatment Outcome , Transplantation, Autologous , Central Nervous System Neoplasms/drug therapy , Retrospective Studies , Observational Studies as TopicABSTRACT
C-X-C chemokine receptor 4 (CXCR4) is a transmembrane chemokine receptor involved in growth, survival, and dissemination of cancer, including aggressive B-cell lymphoma. MRI is the standard imaging technology for central nervous system (CNS) involvement of B-cell lymphoma and provides high sensitivity but moderate specificity. Therefore, novel molecular and functional imaging strategies are urgently required. Methods: In this proof-of-concept study, 11 patients with lymphoma of the CNS (8 primary and 3 secondary involvement) were imaged with the CXCR4-directed PET tracer 68Ga-pentixafor. To evaluate the predictive value of this imaging modality, treatment response, as determined by MRI, was correlated with quantification of CXCR4 expression by 68Ga-pentixafor PET in vivo before initiation of treatment in 7 of 11 patients. Results:68Ga-pentixafor PET showed excellent contrast with the surrounding brain parenchyma in all patients with active disease. Furthermore, initial CXCR4 uptake determined by PET correlated with subsequent treatment response as assessed by MRI. Conclusion:68Ga-pentixafor PET represents a novel diagnostic tool for CNS lymphoma with potential implications for theranostic approaches as well as response and risk assessment.
Subject(s)
Central Nervous System Neoplasms/diagnostic imaging , Lymphoma, B-Cell/diagnostic imaging , Receptors, CXCR4/metabolism , Aged , Aged, 80 and over , Central Nervous System Neoplasms/therapy , Coordination Complexes , Female , Gallium Radioisotopes , Humans , Lymphoma, B-Cell/therapy , Male , Middle Aged , Peptides, Cyclic , Treatment OutcomeABSTRACT
OBJECTIVES: Chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab (R-CHOP) is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL). However, management of elderly patients is challenging as critical comorbidities often account for increased number of treatment-related complications. PATIENTS AND METHODS: In the past 8 yrs, we have treated elderly patients with a full-dose R-CHOP regimen by splitting the administration of cyclophosphamide and doxorubicin over 2 days (R-split-CHOP) to reduce peak plasma level. Here, we retrospectively analyzed the results of 30 patients with newly diagnosed DLBCL. RESULTS: The overall response rate was found to be 87%, the overall survival probability after 3 yrs was 60.6% (95% CI, 42.1%-79.0%), and the progression-free survival probability was 49.7% (95% CI, 30.4%-68.9%). Grade 3/4 infectious complications were reported in 30% of patients, yet no treatment-related deaths occurred. CONCLUSION: We suggest that R-split-CHOP could be a valuable option to safely administer full-dose-intensity R-CHOP to elderly patients at risk of treatment-related complications.
