Phase 2 Study of Daratumumab in Combination with Thalidomide and Dexamethasone in Asian Patients with Relapsed/Refractory Myeloma (RRMM) - Interim Analysis of a Trial By the Asian Myeloma Network (AMN)
Authors: Chng Wee-Joo , Lin Cindy , Li Xinhua , Nagarajan Chandramouli , Yoon Sung-Soo , Durie Brian G.M. 
Published: February 2021

Background
Daratumumab is an anti-CD38 antibody with single agent activity in relapsed refractory myeloma. It has synergistic efficacy when combined with proteasome inhibitors (bortezomib and carfilzomib) or lenalidomide. However to date, the usefulness of the addition of thalidomide to Daratumumab has not been reported. This is particularly relevant as in much of Asia, combinations of 2 novel agents are not reimbursed and hence not accessible to most patients.
Method
We conducted a prospective trial of daratumumab (16mg/kg once a week for 8 weeks followed by once every 2 weeks for 16 weeks and then once every 4 weeks thereafter) plus thalidomide 100mg daily plus dexamethasone (40mg once weekly) in myeloma patients who have relapsed and/or refractory myeloma with up to 6 prior lines of treatment from Singapore, and Korea (NCT03143036). The trial was started in April 2018 and is ongoing. To date,42 of 70 patients have been recruited. This interim report presents data available up till the data cut-off date of 23 June 2020.
Results
Thirty-six patients have available base line information and safety data. 72% of patients are male and median age of the cohort is 67 years old. 39% and 25% of patients are International Stage System (ISS) stage 2 and 3 respectively. 50% of patients have abnormal creatinine clearance. Median prior line of treatment is 2. 94% of patients have prior Bortezomib, 33% had prior Carfilzomib and 17% had prior ixazomib. 58% had prior thalidomide and 44% had prior lenalidomide. 61% of patients had prior high dose melphalan and stem cell transplantation. 36% of patients required dose reduction of thalidomide or dexamethasone. 100% of patients experience adverse events (AEs) of any grade (25% of episodes grade 3 or higher), with 45% of these episodes related to the study drugs. 69% of patients experienced serious AEs (SAEs) of any grade (49% of episodes grade 3 or higher), with 34% of these episodes related to the study drugs. Almost all of these events are related to cytopenia and infections. Only 1 patient experienced grade 3 peripheral neuropathy, and 2 patients experiencegrade 3 renal impairment. Interestingly, only 2 patients develop an infusion reaction but both were able to complete the infusion with a temporary interruption, addition of montelukast and anti-histamines and resuming the infusion at a slower rate. At a median follow-up of 10.4 months for surviving patients, 7 of the 36 patients have died, and 11 have progressed. Five patients withdrew due to toxicity. Of the 36 patients included in this interim analysis, 3 achieved sCR, 3 CR, 10 VGPR, 10 PR giving an overall response rate of 72%.
Conclusion
This is the first study of Daratumumab combined with thalidomide and dexamethasone in Asian patients with RRMM. The combination appears to be highly active and well tolerated with manageable toxicity. This low cost daratumumab combination would be a good option for relapsed myeloma patients especially in countries where the treatment cost and reimbursement for combination containing 2 novel agents is not feasible or unavailable.

Disclosures
Chng: Amgen: Honoraria, Research Funding; Abbvie: Honoraria; Novartis: Honoraria; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Yoon:Kyowahako Kirin: Research Funding; F. Hoffmann-La Roche: Other: All authors received support for third-party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland., Research Funding; Janssen: Consultancy; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; YuhanPharma: Research Funding. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy.