title: Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma.
abstract: The efficacy and favorable safety profile of daratumumab monotherapy in multiple myeloma (MM) was previously reported. Here, we present an updated pooled analysis of 148 patients treated with daratumumab 16 mg/kg. Data were combined from part 2 of a first-in-human phase 1/2 study of patients who relapsed after or were refractory to ≥2 prior therapies and a phase 2 study of patients previously treated with ≥3 prior lines of therapy (including a proteasome inhibitor [PI] and an immunomodulatory drug [IMiD]) or were double refractory. Among the pooled population, patients received a median of 5 prior lines of therapy (range, 2 to 14 prior lines of therapy), and 86.5% were double refractory to a PI and an IMiD. Overall response rate was 31.1%, including 13 very good partial responses, 4 complete responses, and 3 stringent complete responses. The median duration of response was 7.6 months (95% confidence interval [CI], 5.6 to not evaluable [NE]). The median progression-free survival (PFS) and overall survival (OS) were 4.0 months (95% CI, 2.8-5.6 months) and 20.1 months (95% CI, 16.6 months to NE), respectively. When stratified by responders vs stable disease/minimal response vs progressive disease/NE, median PFS was 15.0 months (95% CI, 7.4 months to NE) vs 3.0 months (95% CI, 2.8-3.7 months) vs 0.9 months (95% CI, 0.9-1.0 months), respectively, and median OS was NE (95% CI, NE to NE) vs 18.5 months (95% CI, 15.1-22.4 months) vs 3.7 months (95% CI, 1.7-7.6 months), respectively. No new safety signals were identified. In this pooled data set, daratumumab 16 mg/kg monotherapy demonstrated rapid, deep, and durable responses, with a clinical benefit that extended to patients with stable disease or better.
authors.affiliation: Levine Cancer Institute/Carolinas HealthCare System, Charlotte, NC;
authors.forename: Saad Z
authors.initials: SZ
authors.lastname: Usmani
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Abramson Cancer Center and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Weiss
authors.affiliation: Vejle Hospital and University of Southern Denmark, Vejle, Denmark;
authors.forename: Torben
authors.initials: T
authors.lastname: Plesner
authors.affiliation: Tom Baker Cancer Center-University of Calgary, Calgary, AB, Canada;
authors.forename: Nizar J
authors.initials: NJ
authors.lastname: Bahlis
authors.affiliation: Cross Cancer Institute, Edmonton, AB, Canada;
authors.forename: Andrew
authors.initials: A
authors.lastname: Belch
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA;
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.affiliation: Department of Hematology, VU Medical Center, Amsterdam, The Netherlands;
authors.forename: Henk M
authors.initials: HM
authors.lastname: Lokhorst
authors.affiliation: Division of Hematology/Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC;
authors.forename: Peter M
authors.initials: PM
authors.lastname: Voorhees
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.affiliation: Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY;
authors.forename: Ajai
authors.initials: A
authors.lastname: Chari
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA;
authors.forename: A Kate
authors.initials: AK
authors.lastname: Sasser
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA;
authors.forename: Amy
authors.initials: A
authors.lastname: Axel
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ; and.
authors.forename: Huaibao
authors.initials: H
authors.lastname: Feng
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA;
authors.forename: Clarissa M
authors.initials: CM
authors.lastname: Uhlar
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA;
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ; and.
authors.forename: Imran
authors.initials: I
authors.lastname: Khan
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA;
authors.forename: Tahamtan
authors.initials: T
authors.lastname: Ahmadi
authors.affiliation: Karolinska Institute, Division of Hematology, Department of Medicine, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
authors.forename: Hareth
authors.initials: H
authors.lastname: Nahi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality*; D012008:Recurrence; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; C556306:daratumumab