Outcomes of Vdpace for Relapsed/Refractory Multiple Myeloma in the Era of Daratumumab Based Therapy

Abstract

Background: Although the number of therapeutic options for patients with relapsed/refractory multiple myeloma (RRMM) has increased substantially, it still remains incurable and there remains a significant unmet need for treatment options for highly refractory patients. In this single-center real-world retrospective analysis, we evaluated the efficacy and safety of VDPACE (bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide) as a salvage therapy in the era of daratumumab. Methods: We retrospectively analyzed 88 patients with RRMM who received at least 1 cycle of VDPACE, between 1/2016 till 6/2023 at the University of Kansas Health System in collaboration with the U.S Myeloma Innovations Research Collaborative (USMIRC). VDPACE consists of Bortezomib 1 mg/m2 subcutaneous on days 1, 4, 8 and, 11, doxorubicin 10 mg/m2 continuous infusion (CI) x 4 days, cisplatin 10 mg/m2 CI x 4 days, cyclophosphamide 400 mg/m2 CI x 4 days and etoposide 40 mg/m2 CI x 4 days. In this patient population, we identified two groups - 28 patients who were naïve to daratumumab (DN) and 60 patients who were refractory to daratumumab (DR). Descriptive analysis was performed on available data for patient characteristics, disease course and outcomes differentiating these two groups. Adverse events were graded based on the CTCAE v5.0 criteria. Responses to therapy including overall response rate (ORR), complete response or better (≥CR), and very good partial response (VGPR) were evaluated using the International Myeloma Working Group (IMWG) criteria. The Kaplan-Meier method was used for progression free survival (PFS) and overall survival (OS) assessment. Results: The median age for the entire patient population was 63 years (41-77). Median lines of therapies (LOT) in DN vs DR groups were 2 (1-10) vs 5 (1-10), respectively (Table 1). The ORR and ≥VGPR in DR vs DN was 53% vs 50% and 15% vs 29%, respectively. With a median follow-of 11.3 months (95% CI, 4.03-27), the median PFS for the entire patient population was 4 months (95% CI, 2.97-5.43) while the median OS was 11.1 months (95% CI, 6.97-14.9). However, the median OS for DN was 15.9 months (95% CI, 8.73-29.5) compared to 7.03 months ((95% CI, 6.27-13.57) p=0.06) for the DR group. See Figure 1. Treatment related toxicities were similar in both groups. The most common grade III/IV hematological toxicities were neutropenia (96% vs 93%, p=0.99), thrombocytopenia (93% vs 80% p=0.2), lymphopenia (89% vs 95%, p=0.3), and anemia (79% vs 73%, p=0.79). Transfusion of packed red blood cells (64% in DN vs 68% in DR group) and platelet (61% vs 80%) were common in both groups. Rates of neutropenic fever were similar in both groups; 46% in the DN vs 35% in the DR group, p=0.62, with pneumonia being the most common infection seen in 11% vs 5% of the patients, respectively. Sixty-day Rehospitalization rates in the two groups were 21% vs 50%. There was no treatment-related mortality reported with this regimen. The difference in OS after VD-PACE in DR and DN patients could be explained by higher no of prior LOT, presence of high risk cytogenetics, double refractory status, and limited options available for salvage. Conclusions: Our study shows that while the response rates with VDPACE were comparable in the two groups, there was a higher median OS in the DN. Hematologic adverse events were common in both groups, but the rate of re-hospitalization was higher in the DR group. Based on these results, VDPACE remains a safe and effective salvage therapy for patients with RRMM. For DR patients receiving VD-PACE, strong consideration should be given to clinical trials given poor long-term outcomes.