Daratumumab, pomalidomide, and dexamethasone (DPd) followed by high dose chemotherapy-Autologous Stem Cell Transplantation leads to superior outcomes when compared to DPd-alone for patients with Relapsed Refractory Multiple Myeloma

Abstract

Background and objectives: While the role of autologous stem cell transplant (ASCT) in the first line therapy for newly diagnosed multiple myeloma is well established, efficacy of ASCT for patients with relapsed refractory multiple myeloma (RRMM) in the era of novel therapeutic agents remains unknown. In this single center retrospective analysis, we evaluated and compared the efficacy and safety outcomes of patients with RRMM treated with daratumumab pomalidomide dexamethasone (DPd) alone versus (vs) DPd followed by ASCT.

Methods: A total of 83 patients with RRMM who were treated with and achieved at least partial response (PR) with DPd were evaluated by electronic medical records. All patients who responded to DPd and were deemed eligible for ASCT proceeded with high dose melphalan followed by autologous stem cell infusion (DPd + ASCT group). Remaining patients continued DPd until disease progression or intolerable toxicities (DPd-alone group). Responses were evaluated using the International Myeloma Working Group response criteria and toxicities were graded using National Cancer Institute Common Terminology Criteria for Adverse Events. Patient and disease characteristics, as well as efficacy and safety outcomes were summarized using descriptive statistics. Kaplan-Meier analyses were used to estimate progression-free survival (PFS) and overall survival (OS).

Results: A total of 21/83 (25%) patients with RRMM who achieved at least PR to DPd underwent ASCT (DPd + ASCT group) while the remaining 62/83 (75%) continued DPd without ASCT (DPd-alone group). For the entire patient population, median age was 66 years (42-81), 49 (59%) patients were male, 54 (65%) patients had IgG isotype, 21 (25%) patients had R-ISS stage III disease, 51 (61%) patients had high-risk cytogenetics, and 17 (20%) patients had extramedullary disease. Patient age, disease stage, cytogenetic risk profile were well balanced between two groups. A stringent complete response was seen in 10 (16%) and 12 (57%) patients in the DPd-alone and DPd + AST groups, respectively. Median PFS was 17.5 months in the DPd-alone vs 42.2 months (p=0.006) in the DPd + ASCT group. Median OS was 38.1 months in the DPd-alone group vs not reached in the DPD + ASCT group (p=0.009). The most common grade 3 or 4 treatment-related adverse events (TRAE) were myelosuppression and gastrointestinal toxicities, more commonly seen in the DPd + ASCT group. No treatment-related mortalities were observed in either group.

Conclusion: Patients with RRMM who responded to DPd and underwent HDT-ASCT demonstrated superior depth and duration of remission compared to those who received DPd-alone. Although DPd followed by ASCT is associated with more cytopenias and gastrointestinal toxicities, this treatment appears to be overall safe for patients with RRMM.

Keywords: autologous; daratumumab; multiple myeloma; pomalidomide; relapsed.