The COLUMBA trial examined the efficacy, number of infusion-related reactions, and administration time for SC vs IV daratumumab in R/R multiple myeloma.
CHICAGO-Subcutaneous (SC) administration of daratumumab was as effective as intravenous (IV) administration in patients with relapsed or refractory multiple myeloma, while significantly reducing infusion-related reactions and administration time, according to the results of the COLUMBA trial (abstract 8005). The data were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.
“One of the main problems for daratumumab is the median duration of infusion because you know the first infusion lasts 7 hours, the median duration of the second is 4.3 hours, and the third and subsequent is 3.4 hours,” said presenter Maria-Victoria Mateos, MD, PhD, of University Hospital of Salamanca, Spain. “In order to optimize daratumumab administration, daratumumab subcutaneous was developed, a version of daratumumab co-formulated with recombinant human hyaluronidase PH20.”
The non-inferiority trial randomly assigned 522 patients with relapsed or refractory myeloma to SC daratumumab (1,800 mg plus rHuPH20) or IV daratumumab (16 mg/kg) weekly for cycles 1 and 2, every 2 weeks for cycles 3 to 6, and every 4 weeks thereafter.
Patients had received a median of four prior lines of therapy, and all had received both a proteasome inhibitor and an immunomodulatory agent. Overall response rate and pre-dose C3D1 daratumumab maximum Ctrough at cycle 3 day 1 were co-primary endpoints.
At a median follow-up of 7.5 months, the proportion of patients discontinuing the trial was identical in both arms. Additionally, the median number of cycles completed was similar for patients assigned to the SC and IV formulations.
However, daratumumab SC reduced administration time compared with IV administration. The median duration of injection for the SC formulation was 5 minutes compared with 421 minutes for the first infusion of IV daratumumab, 255 minutes for the second infusion, and 205 minutes for the third infusion.
The overall response rate for patients assigned to the SC formulation was slightly lower than the IV formulation (37.1% vs 41.1%; relative risk, 1.11; 95% CI, 0.89–1.37), but Mateos pointed out that the lower bound of the confidence interval was higher than the 60% specified for non-inferiority in the study design.
An analysis of the maximum Ctrough concentration showed the ratio of daratumumab SC over daratumumab IV was 107.93% (90% CI, 95.74%–121.67%), but the lower limit of 90% confidence CI was 95%, higher than the 80% specified for non-inferiority in the trial design.
Response was comparable across all subgroups, including body weight, Mateos said, and progression-free and overall survival were comparable for the two routes of administration.
Infusion-related reactions occurred in 34.5% of patients assigned to IV administration compared with 12.7% of patients assigned to SC administration (odds ratio, 0.28; 95% CI, 0.1–-0.44; P< .0001). In both arms, most infusion-related reactions were grade 1 or 2 with few patients developing grade 3 reactions. Daratumumab SC did not result in more toxicities, but there was a slightly higher incidence of neutropenia.
Finally, a questionnaire evaluating patient satisfaction showed that patients assigned to the SC formulation were more satisfied with their cancer therapy than patients on daratumumab IV.
“These results support the use of flat dose 1,800 mg daratumumab SC, which is comparable to daratumumab IV,” Mateos said.
The study discussant, Faith Davies, MD, MBBCh, MRCP, FRCPath, of Perlmutter Cancer Center at NYU Langone, acknowledged that this study of delivery route recognizes some of the problems associated with standard delivery of daratumumab.
“We have seen that isatuximab has quicker delivery, but clearly this subcutaneous [daratumumab] route is another option for our patients,” Davies said. “We do need to remember, though, that there were some later side effects, so we need to keep an open [eye] for those and learn more about managing local reactions.”