PB2185 DARATUMUMAB MONOTHERAPY IN REAL LIFE COMMUNITY SETTING OF REFRACTORY MYELOMA PATIENTS: A RETROSPECTIVE UNICENTRIC STUDY
Authors: Del Fabro V. , Sapienza G. , PARISI M. S. , leotta V. , leotta S. , parrinello N. L. , gennaro G. , romano A. , di raimondo F. , conticello C. 
Published: June 2019

Background:

Daratumumab (DARA) is a first in class CD38‐directed monoclonal antibody approved for the treatment of relapsed and/or refractory multiple myeloma (RRMM). In phase I/II and III trials, DARA monotherapy can induce an overall response (partial response or better) in about one third of patients, with rapid and durable responses. High occurrence of all grade of Infusion‐Related Reactions–IRRs‐ has been described (up to 50% of cases), including 5% of at least grade 3 IRRs. In some cases IRRs can induce infusion delayed or interruption and need of patient hospitalization. It is known that highest risk of reaction is during the first or second exposure to DARA.

Aims:

To describe DARA‐related IRR in real life clinical setting, particularly management of first infusion.

Methods

Starting from April 2017, 13 RRMM patients received DARA intravenously (i.v.) according to the manufacture schedule. To reduce IRRs, only the first dose was split in 2 administrations within 24 hours. One hour after standard premedication the first 250 ml were given starting at infusion rate of 50 mL/hour as schedule. After 24 hours, premedication was given and the remaining 750 mL were infused as schedule.

Results:

Our cohort included 13 heavily pre‐treated patients (n = 76 M/F), most of them double refractory (n = 11) with a median of 4 previous lines (range 1‐13). Median age was 61 years (range 46‐74). At least 3 treatment cycles were given to 11 (84%) patients, two cycles to 12 patients.

At the first day of infusion, 10/13 patients had a grade 1‐2 IRR treated with suspension of infusion for about 20‐30 minutes followed by infusion of antipyretics or antihistamine. Restarting DARA infusion was safe and comfortable. IRRs were cough in 4 patients, congestion and runny nose in 4 patients, throat tightness and dyspnea in 3 patients and chills in 1 patient. Rarely, a second manifestation of IRRs occurred again. Symptoms were treated in the same way and resolved promptly.

None of our patients discontinued treatment for IRR, and up to now 5 patients are completing the third cycle, six patients died for disease progression (2 after the first cycle, 1 after the second cycle, 1 after the third cycle) while for the remaining 6 treatment is ongoing. 6/13 patients had severe adverse events (anemia and neutropenia ≥ grade 3, NCCN) and 2/13 pneumonia grade 3, requiring hospitalization.

Clinical benefit was evident for 7/13 patients, with 53% of overall response rate (after 8 infusions): 1 patient achieved a CR, 2 achieved a very good partial remission (VGPR), 4 patients achieved partial response (PR), a patient achieved stable disease (SD).

Progression occurred in 2 patients after 1 cycle, 2 patients after 2 cycles and two other after 3 cycles. Overall median PFS was 13 months, median OS was not reached.

Summary/Conclusion:

In line with published clinical trials in the setting of RRMM, DARA monotherapy is efficacious in RRMM patients with an overall response rate of 53%. According to our schedule, IRRs are weakly and occur only the first day, when the infusion rate is increased from 50 to 100 mL/hour and it can be reduced by splitting the infusion over 24 hours.