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Feasibility of CXCR4-directed radioligand therapy in advanced diffuse large B cell lymphoma.

We have recently reported on our experience with C-X-C-motif chemokine receptor 4- (CXCR4-) directed radioligand therapy (RLT) in multiple myeloma and acute leukemia. Methods: Six patients with heavily pre-treated relapsed diffuse large B cell lymphoma (DLBCL) (3 males, 3 females; aged, 54±8 years) underwent CXCR4-directed RLT in combination with conditioning chemotherapy and allogeneic stem cell transplantation (SCT). In 2 patients, radioimmunotherapy (RIT) targeting CD20 or CD66 was added to enhance anti-lymphoma activity. Endpoints were incidence and severity of adverse events, progression-free and overall survival. Results: RLT as well as additional RIT were well-tolerated without any acute adverse events or changes in vital signs. Successful engraftment was recorded after a median of 11 days (range, 9-13 d). In the 4 patients who were available for follow-up (one patient died of CNS aspergillosis 29 days, another of sepsis in aplasia 34 days after after RLT), CXCR4-directed RLT resulted in partial response in 2/4 cases (both treated with additional RIT) and mixed response in the remaining 2 subjects. Response duration was rather short-lived with median progression-free survival of 62 days (range, 29-110 d) and median overall survival of 76 days (range, 29-313 d). Conclusion: CXCR4-directed RLT (in combination with additional RIT) as a conditioning regimen prior to allogeneic SCT in DLBCL is feasible.

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