Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma

Torben Plesner, Hendrik-Tobias Arkenau, Peter Gimsing, Jakub Krejcik, Charlotte Lemech, Monique C. Minnema, Ulrik Lassen, Jacob P. Laubach, Antonio Palumbo, Steen Lisby, Linda Basse, Jianping Wang, A. Kate Sasser, Mary E. Guckert, Carla de Boer, Nushmia Z. Khokhar, Howard Yeh, Pamela L. Clemens, Tahamtan Ahmadi, Henk M. Lokhorst and Paul G. Richardson

Key points

  • Daratumumab plus lenalidomide/dexamethasone elicited an overall response rate of 81% (63% very good partial response or better).

  • Adverse events were manageable and in accord with the individual toxicity profiles of daratumumab and lenalidomide/dexamethasone.


Daratumumab, a human CD38 IgG1κ monoclonal antibody, has activity as monotherapy in multiple myeloma (MM). This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM. Part 1 (dose-escalation) evaluated 4 daratumumab doses plus lenalidomide (25 mg/day p.o. on Days 1 21 of each cycle) and dexamethasone (40 mg/week). Part 2 (dose-expansion) evaluated daratumumab at the recommended phase 2 dose (RP2D) plus lenalidomide/dexamethasone. Safety, efficacy, pharmacokinetics, immunogenicity and accelerated daratumumab infusions were studied. In Part 1 (13 patients), no dose-limiting toxicities were observed; 16 mg/kg was selected as the R2PD. In Part 2 (32 patients), median time since diagnosis was 3.2 years, with a median (range) of two (one-three) prior therapies, including proteasome inhibitors (91%), alkylating agents (91%), autologous stem cell transplant (78%), thalidomide (44%), and lenalidomide (34%); 22% were refractory to last line of therapy. Grade 3/4 adverse events (≥5%) included neutropenia, thrombocytopenia, and anemia. In Part 2, infusion-related reactions (IRRs) occurred in 18 patients (56%); most were grade ≤2 (grade 3, 6.3%). IRRs predominantly occurred during first infusions and were more common during accelerated infusions. In Part 2 (median follow-up of 15.6 months), overall response rate was 81% with 8 (25%) stringent complete responses, 3 (9%) complete responses, and 9 (28%) very good partial responses. Eighteen-month progression-free and overall survival rates were 72% (95% CI, 51.7-85.0) and 90% (95% CI, 73.1-96.8), respectively. Daratumumab plus lenalidomide/dexamethasone resulted in rapid, deep, durable responses. The combination was well-tolerated and consistent with the safety profiles observed with lenalidomide/dexamethasone or daratumumab monotherapy.

  • Submitted July 7, 2016.
  • Accepted August 5, 2016.