7517 Background: Frontline therapy for patients with multiple myeloma (MM) has mainly consisted of a proteasome inhibitor and an immunomodulatory imide drug (IMiD). Anti-CD38 monoclonal antibodies are fast becoming incorporated into frontline regimens, but many patients experiencing relapse today remain naïve to this drug class. While quadruplet therapies have become a standard-of-care in the newly diagnosed setting, they have not been well studied in patients with relapsed/refractory MM (RRMM). Here, we report the final analysis of a phase 2 Multiple Myeloma Research Consortium study of daratumumab combined with carfilzomib, pomalidomide, and dexamethasone in RRMM (NCT01665794). Methods: Eligible patients had documented MM with 1-3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug. Prior exposure to a CD38-directed monoclonal antibody was exclusionary. Dose and frequency were described previously. The primary endpoint was the rate of near complete response (nCR) after 4 cycles of DaraKPd; secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results: A total of 28 patients were treated with DaraKPd. Patients had received a median of 1 prior line of therapy (range 1-3), including 24 (85.7%) with prior autologous stem cell transplant, and 82% that were refractory to lenalidomide. The study reached the statistical threshold for efficacy (nCR of 39%; 95% CI 22-59%), and the study was stopped early as a result. At a median follow-up of 70.2 months, the median progression-free survival (mPFS) was 38.3 months (95 % CI 18.4 mo-not reached NR) and median OS (mOS) was not reached. The 36-month PFS and OS were 54% (95% CI 35-70%) and 75% (95% CI 57-87%), respectively. High-risk cytogenetics, as defined by the presence of t(4;14), t(14;16), t(14;20), deletion 17p, and 1q gain or amplification, were present in 18 (64%) patients. The mPFS in the high risk group was 42.8 mo (18.4-NR) and mOS was not reached. For patients with standard-risk cytogenetics, neither the mPFS nor mOS were reached. Of the 26 patients evaluable for MRD negativity by flow cytometry (limit of detection 10 -5 ), 17 (65%) achieved MRD-negativity and 11 (42%) had sustained MRD negativity for ≥1 year. Among patients with MRD-negativity as best response, mPFS was 69.4 mo (18.9-NR) compared to 14.0 mo (1.2-NR) in patients with MRD positivity (p = 0.002). There were no new safety signals or treatment-related deaths. Conclusions: With nearly 6 years of follow-up, DaraKPd in lenalidomide-exposed and anti-CD38 monoclonal antibody-naïve RRMM showed deep and durable responses, with a mPFS of 38.3 months and 36-month OS of 75%. These long-term follow-up data support DaraKPd as a safe and effective treatment in patients with RRMM. Clinical trial information: NCT01665794 .
Cooperrider et al. (Thu,) studied this question.