Daratumumab, Pomalidomide, and Dexamethasone (DPd) As Salvage Treatment for Relapsed/Refractory Myeloma Eligible for High-Dose Chemotherapy/Autologous Stem Cell Transplantation

Introduction: The number of therapeutic options for patients with relapsed refractory multiple myeloma (RRMM) has increased significantly in recent years. There is no standard salvage treatment for these patients who relapse after initial ASCT. Our institute treated a series of patients with salvage therapy consisting of the novel triplet daratumumab, pomalidomide and dexamethasone (DPd) followed by high dose chemotherapy with ASCT. We report the early outcomes of these patients.

Methodology: We treated 12 patients with RRMM at the University of Kansas Health System between May 2016 and July 2018, with DPd salvage therapy for 3-4 cycles followed by HDCT/ASCT. DPd was given as Daratumumab 16 mg/kg weekly for cycles 1-2, every 2 weeks for cycles 3-6, and then every 4 weeks; pomalidomide 4 mg orally on days 1-21 of a 28-day cycle; and dexamethasone 20 or 40 mg orally weekly. Provided patients responded they were then eligible for ASCT using either a melphalan 200 or 140 mg/m2 preparative regimen after stem cell collection if cells were not already available. Descriptive analyses were performed on available data for patient characteristics, disease course, and outcomes. Responses were evaluated using the IMWG criteria.

Results: Among the 12 patients included in the analysis, the median age at the time of receiving DPd was 64 years (range 57-70). Ten patients (83%) had IgG isotype, 7 patients (58%) had ISS stage II-III disease at diagnosis, 3 patients (25%) had high risk cytogenetics, and 3 patients (25%) had extramedullary disease. Median number of previous therapies was 2 (1-10). Ten patients (83%) were bortezomib refractory, 11 patients (92%) were refractory to lenalidomide, 5 patients (42%) were refractory to carfilzomib and 2 patients (13%) were refractory to pomalidomide. Ten patients (83%) were refractory to both a proteasome inhibitor and immunomodulatory agent. Ten patients (88%) received ASCT prior to DPd. Median time from diagnosis to treatment with DPd and ASCT was 12 months (4-138). Median number of DPd cycles received was 4 (2-7) cycles and median duration of treatment was 5 months (2-30).

At a median follow-up of 10.5 months, overall response rate (ORR) for all patients after salvage treatment with DPd but prior to ASCT was 83% (Table 1). All patients received HDCT/ASCT with these responses deepening in all but 2 of the patients (Figure 2), ORR on day 100 was 12 (100%), 5 patients (41%) achieved sCR, 2 patients (17%) achieved CR, 3 patients (25%) achieved VGPR, 2 patients (17%) achieved PR. Treatment-related mortality on day 100 was 0. Three patients progressed after 4.3, 6.6, and 8.9 months. One patient died after 9.7 months due to progressive disease.

Conclusions: Our single institution experience highlights that for patients with RRMM, novel therapies are needed to obtain deep responses. We used DPd as salvage therapy to achieve an 83% response rate in this population of patients, enabling all patients to then proceed to HDCT/ASCT safely and nearly all responses were deepened. DPd can be utilized as an excellent salvage regimen in RRMM followed by HDCT/ASCT. However, we believe that this approach should be further studied to identify the long term clinical benefits of the treatment.

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