MM-570 Real-World Results with Daratumumab-Bortezomib-Dexamethasone (dvd) Protocol – or Sometimes Less Might Be More

Context:The anti-CD38 antibody daratumumab has been available in Hungary since 2017 for multiple myeloma (MM) patients, used mainly in combinations with lenalidomide or bortezomib.As the majority of patients are refractory to lenalidomide by the time of third-line treatment, where daratumumab is financed, we generally prefer the bortezomib (DVd) combination.Objective: To evaluate our real-world results compared to CASTOR study outcomes.Design: Retrospective overview of the mandatory reporting system for all daratumumab treatments and our own clinical data from January 2017 to May 2023.Setting: University clinic with a myeloma center.Patients: Every patient with MM that received at least 1 cycle of daratumumab in combination with bortezomib and dexamethasone until May 2023 was included (57 patients).We evaluated the number of previous lines of therapy, lenalidomide refractivity, and cytogenetic risk factors.Main Outcome Measures: Hematologic response rates and progression-free survival (PFS).Results: Unlike in the CASTOR study, where patients received daratumumab in the median second line and only 18% were refractory to lenalidomide, our patients were treated in the median third line and 75% were refractory to lenalidomide.Unsurprisingly, median PFS at our clinic, 11.4 months, proved worse than the median 16.8 months PFS in CASTOR.Remarkably however, the comparison of only third-or fourth-line treated patients showed a significantly better median PFS at our clinic (14.9 vs 9.8 months).This is most likely due to different bortezomib treatment regimens: while in the CASTOR study bortezomib was administered twice a week in the beginning and not at all after 6 months, our protocol included weekly doses at the start and continued bortezomib treatment concurrently with the daratumumab infusions until progression.Conclusions: A less dose-intensive bortezomib protocol may provoke fewer therapylimiting neuropathies and allow for the continuation of combination therapy, utilizing the synergism of proteasome inhibition and anti-CD38 antibodies and thereby prolonging PFS.