Daratumumab Combination Demonstrates Efficacy in Relapsed/Refractory Myeloma With EMD

According to findings from a phase 2 study (NCT04065308) exploring daratumumab (Darzalex) in combination with dexamethasone, cyclophosphamide, etoposide (VP-16), and cisplatin (Platinol) as treatment for patients with relapsed or refractory extramedullary multiple myeloma, the regimen (Dara-DCEP) was effective in controlling the disease following bortezomib (Velcade) failure.

Based on best responses observed in the study, the complete remission (CR) rate among patients was 35.5% (n = 11/31), and the overall response rate (ORR) was 67.7%. Additionally, with a median follow-up of 11 months, the median progression-free survival (PFS) was 5 months, whereas overall survival (OS) was 10 months. In a comparison between “responders” who had partial or better responses during treatment and “non-responders” who did not, responders had longer median PFS and OS rates. Among patients described as responders and non-responders, respectively, the median PFS was 6 months vs 3 months (P <.0001), and the median OS was not reached vs 5 months (P = 0.0001).

During the induction phase, investigators administered the Dara-DCEP regimen once every 4 weeks for a total of 3 treatment cycles. The regimen included a weekly 16 mg/kg intravenous dose of daratumumab on weeks 1 to 8 followed by a bi-weekly 16 mg/kg dose on weeks 9 to 12, 40 mg of dexamethasone taken intravenously or by mouth on days 1 to 4, 400 mg/m² of intravenous cyclophosphamide on days 1 to 4, 40 mg/m² of intravenous etoposide on days 1 to 4, and 10 mg/m² of intravenous cisplatin on days 1 to 4. Following the induction phase of treatment, response evaluations were completed per International Myeloma Working Group guidelines, which determined patient eligibility for autologous stem cell transplantation (ASCT). Patients who had at least a partial recovery (PR) and were ASCT eligible received ASCT conditioning based on physician’s choice followed by a daratumumab maintenance schedule consisting of a 16 mg/kg dose every 2 weeks for 6 cycles then a 16 mg/kg dose every 4 weeks for 2 cycles. Patients who were ineligible for ASCT only had the same durvalumab maintenance schedule.

The primary end point of the study was CR rate. Secondary end points included ORR, PFS, OS, and adverse effects (AEs).

This open-label, multi-center, non-randomized trial treated 32 patients with extramedullary multiple myeloma that relapsed or was refractory following bortezomib-based treatment. Patients 19 years or older were eligible to enroll on the study. Additional inclusion criteria included having an ECOG performance status of 0 to 2 and having adequate bone marrow function.

Of 33 enrolled patients, the median age was 59 years (range, 35-73). Of 32 patients who received at least 1 dose of the investigational therapy, 71.9% (n = 23/32) had soft tissue masses in extra-osseous locations with or without bone lesions, and 28.1% (n = 9/32) only had bone-related plasmacytomas. Risk stratification data was available for 23 patients, 16 of whom (69.6%) were classified as high risk. Patients received a median of 3 (range, 1-5) prior lines of therapy, and median time to study screening from a multiple myeloma diagnosis was 26 months (range, 3-101). Prior to study enrollment, 100% (n = 32/32) of patients were previously exposed to bortezomib, 78.1% (n = 25/32) were exposed to carfilzomib (Kyprolis), and 90.6% (n = 29/32) were exposed to lenalidomide (Revlimid).

In terms of hematologic AEs, thrombocytopenia most notably occurred with increasing incidence with cumulative Dara-DCEP cycles. A total of 36% (n = 9/25) experienced grade 3 or more thrombocytopenia in the third Dara-DCEP cycle. During the second Dara-DCEP cycle, 6 patients had documented infections: 1 case of pneumonia, 2 cases of Staphylococcus aureus bacteremia, 2 cases of disseminated herpes zoster infection, and 1 case of localized herpes zoster infection.

In terms of non-hematologic AEs, the most common any-grade AEs included nausea (22.6%), dyspepsia (12.9%), diarrhea (12.9%), and stomatitis (12.9%). Additionally, 2 deaths occurred during the study. One patient died due to underlying multiple myeloma progression. Another patient died due to combined bacterial and cytomegalovirus pneumonia, which was classified as a treatment-related mortality because the patient was in PR at the time.

Reference

Byun JM, Min C, Kim K, et al. Phase II trial of daratumumab with DCEP in relapsed/refractory multiple myeloma patients with extramedullary disease. J Hematol Oncol. 2022;15(150). doi:10.1186/s13045-022-01374-5