Background. In the last twenty years, the outcome of multiple myeloma (MM) has markedly improved. Daratumumab is the first anti-CD38 monoclonal antibody (mAb) recently approved for the treatment of relapsed refractory multiple myeloma (RRMM). In this study we have evaluated the efficacy of daratumumab single agent and daratumumab plus pomalidomide and dexamethasone in low and high risk RRMM patients.
Design and Methods. From November 2015 to March 2016, 25 and 39 RRMM patients were treated with therapy using daratumumab single agent (Group 1: median age 67, range 40-83) and daratumumab plus pomalidomide and dexamethasone respectively (Group 2: median age 71, range 45-87). In both groups, patients received daratumumab IV 16 mg/kg once a week (weeks 1-8), followed by every other week (weeks 9-24) and then once a month until disease progression or unacceptable toxicities. In Group 2 pomalidomide was administered at dosages from 1 mg to 4 mg daily according to tolerability for 21 days every 28 days, along with dexamethasone 40 mg weekly.
The median time form the time of diagnosis was 7.1 years and 5.5 years in Group 1 and Group 2 respectively. In both groups, patients had received a median of 4 prior treatments. In Group 1, 80% of the patients had disease refractory to the last therapy received, 68% had disease double refractory to IMiDs and PIs, and 28% (7 patients) had GEP high risk signature. In Group 2, 78% of the patients had disease refractory to last therapy, 84% had double refractory disease and 37% (14 patients) had high GEP risk signature.
Results. In the single agent group, the overall response rate (ORR) was 28%: CR 4% (1 patient), 4% VGPR (1 patient), PR 20% (5 patients). With a median follow up of 3.5 months, 48% of patients were still on treatment and 52% had discontinued treatment for disease progression. The ORR according to last GEP70 was 40% and 0% in the low risk and high risk patients respectively. All high risk patients had discontinued treatment for disease progression within the second month of treatment.
In the second group, the ORR was 41%: CR 5% (2 patients), 3% VGPR (1 patient), and 33% PR (13 patients). After a median follow up of 4 months, 77% (30 patients) of patients were still on treatment, 20% (8 patients) discontinued treatment for disease progression and 3% (1 patient) of patients had discontinued treatment for adverse event grade 4. The ORR was 50% (4% CR, 4% VGPR, and 42% PR) in low risk patients and 21% (7% CR and 14% PR) in high risk patients.
Infusion-related reactions were mild (54% of patients had an event of any grade, and 4% and 2% had an adverse event of grade 3 in Group 1 and Group 2 respectively). The most common non hematological adverse event of grade 3 or 4 was pneumonia (4% and 8% in Group 1 and Group 2 respectively). PFS of Group 1 and 2 are shown in Figure 1.
Conclusion. Daratumumab single agent had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma, and the combination of daratumumab with pomalidomide and dexamethasone was well tolerated and improved the outcome in low risk patients, even in double refractory disease. Encouraging results have been observed as well in patients with high risk GEP 70 signature.
Figure 1 Figure 1.
Davies: Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Morgan:Univ of AR for Medical Sciences: Employment; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Bristol Meyers: Consultancy, Honoraria; Janssen: Research Funding.