The IV formulation of daratumumab, a monoclonal antibody targeting CD38, has been approved as either monotherapy or in combination with standard-of-care regimens for patients with RRMM, or when combined with bortezomib/melphalan/dexamethasone for transplant-ineligible, newly diagnosed patients with MM. However, IV daratumumab is typically infused over hours and is associated with infusion reactions in a substantial percentage of patients.
In the open-label, multicentre, phase 3 COLUMBA trial, 522 adult patients with RRMM were randomly assigned in a 1:1 ratio to receive an SC formulation of daratumumab, including recombinant human hyaluronidase to temporarily break down the hyaluronan barrier to allow for the more rapid administration of large volumes of drug. The formulation was a fixed dose of 1,800 mg once weekly in cycles 1 and 2, every 2 weeks in cycles 3 to 6, and every 4 weeks in cycle 7 and beyond, with each cycle lasting 4 weeks, and administered using alternating left/right abdominal site injections. This was compared with the IV formulation (16 mg/kg once weekly in cycle 1 and 2, every 2 weeks in cycle 3 to 6, and every 4 weeks in cycle 7 and beyond).
The co-primary endpoints of the study were overall response rate and the maximum pre-dose trough concentration of daratumumab on day 1 of cycle 3, with both endpoints analysed for noninferiority. Patient characteristics and disease-related characteristics of the study population included a median age of 67 years, a median of 4 previous lines of therapy, as well as prior treatment with both an immunomodulatory drug and a proteasome inhibitor in all patients.
At a median follow-up of 7.5 months, the overall response rates were 41.1% and 37.1% for patients receiving SC and IV formulations, respectively. In addition, the ratio of the maximum pre-dose trough concentration of daratumumab on day 1 of cycle 3 for SC daratumumab over IV daratumumab was 108%. Furthermore, median PFS was 5.6 months vs 6.1 months for patients receiving the SC and IV formulations of daratumumab, respectively (P=0.9258).
Anaemia, neutropenia, thrombocytopenia, and diarrhoea were the most common treatment-emergent adverse events reported in the study. The 2 study arms showed generally comparable safety profiles, although rates of grade 3/4 neutropenia were slightly higher for patients receiving SC daratumumab (13%) compared with IV daratumumab (8%). The rates of treatment discontinuation due to an adverse event were 7% and 8% for those receiving SC and IV daratumumab, respectively. While 34.5% of patients receiving IV daratumumab experienced infusion reactions, these were reported in only 12.7% of those receiving SC daratumumab. Injection-site reactions occurred in approximately 7% of patients receiving SC daratumumab. Importantly, the median duration of injection for SC daratumumab was 5 minutes compared with infusion times of 421 minutes, 255 minutes, and 205 minutes for patients receiving the first, second, and subsequent infusions of IV daratumumab. A striking difference was noted in assessments of treatment satisfaction over time of patients in the 2 study arms, showing higher levels of satisfaction with treatment for patients receiving SC daratumumab compared with IV daratumumab.
- Mateos M-V, et al. Abstract S823, 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.
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Table of Contents: EHA 2019
Featured articles
Editor Biography
Interview with EHA President Prof. Pieter Sonneveld
Myeloid Malignancies
Residual disease in AML patients prior to stem cell transplant increases relapse risk
Gilteritinib prolongs overall survival in patients with FLT3-mutated relapsed/refractory AML
Initial data on AMV564 in patients with relapsed/refractory AML
Overcoming the ādonāt eat meā signal in AML and MDS
Asciminib plus imatinib in patients with heavily pre-treated chronic myeloid leukaemia
Guadecitabine vs treatment of choice in AML
Lymphoid Malignancies
Unmutated IGHV as predictive factor for venetoclax/obinutuzumab benefit in frontline CLL
CAR-T cell therapy in ALL as breakthrough advance
Brentuximab vedotin continues to demonstrate superior clinical activity in classical Hodgkin lymphoma
Infectious complications mild and not common in patients receiving CAR-T therapy for diffuse large B cell lymphoma
Obinutuzumab/polatuzumab in follicular lymphoma
Exciting survival data for ibrutinib vs placebo in treatment-naĆÆve, early-stage CLL
ASCEND study: Acalabrutinib improves progression-free survival in relapsed/refractory CLL
Venetoclax-obinutuzumab combination elicits high response rates in CLL
Myeloma
CASSIOPEIA trial: Phase 3 results of daratumumab + bortezomib/thalidomide/dexamethasone in multiple myeloma
Chimeric antigen receptor T cell therapy in multiple myeloma
Higher levels of treatment satisfaction without compromising efficacy: subcutaneous daratumumab in RRMM
Adding isatuximab to pomalidomide and dexamethasone improves PFS and ORR in RRMM
Subcutaneous daratumumab + cyclophosphamide, bortezomib, and dexamethasone in patients with newly diagnosed amyloid light chain amyloidosis
Venetoclax for multiple myeloma: effective but some safety concerns
Benign Haematology
New sickle cell drug voxelotor boosts levels of haemoglobin
Positive initial data evaluating the safety and efficacy of IMR-687 for treatment of sickle cell disease
Haematopoietic stem cell transplantation improves stroke risk in children with sickle cell anaemia
Early trial data shows positive results for treating anaemia in patients with end-stage renal failure
Bench-to-Bedside
Transformation of foetal haematopoietic stem and progenitor cells in the background of trisomy 21
Treating thalassemia twice, in mice
Haematopoietic stem cells can sense tissue damage in the gut
Promising news for gene therapy for sickle cell disease
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