In one-year follow-up data from the phase III ANDROMEDA trial, the combination of subcutaneous daratumumab with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) led to high overall and complete response (CR) rates in patients with newly diagnosed amyloid light chain (AL) amyloidosis. The findings were presented at the 24th Congress of the European Hematology Association.
“Daratumumab-based combinations have resulted in deep responses and minimal additional toxicity in multiple myeloma, making such combinations potentially ideal in the treatment of AL amyloidosis,” the authors, led by Raymond Comenzo, MD, from the Tufts University School of Medicine in Boston, explained.
Dr. Comenzo shared data from the 28 patients who were enrolled in the safety run-in phase of ANDROMEDA. Participants had previously untreated AL amyloidosis with at least one involved organ, an Eastern Cooperative Oncology Group score ≤2, estimated glomerular filtration rate ≥20 mL/min/1.73m2, and NT-ProBNP ≤8,500 ng/L.
In the safety run-in portion of the study, patients received daratumumab 1,800 mg (formulated with recombinant human hyaluronidase PH20) administered subcutaneously once a week during cycles 1 and 2, every two weeks during cycles 3 through 6, and every four weeks thereafter for up to two years. Patients also received CyBorD, with cyclophosphamide 300 mg/m2, bortezomib 1.3 mg/m2, and dexamethasone 40 mg, administered once weekly for up to six treatment cycles.
As of the data presentation, 28 participants (median age = 68 years; range = 35-83 years) had received treatment with daratumumab plus CyBorD. Patients had a median of two (range = 1-4) involved organs; the most frequently observed sites of organ involvement were the heart (54%) and kidneys (61%).
Researchers followed patients for a median of 341 days (range = 17-449 days), with median treatment duration of 11 months (range = 0.2-14 months). During this time, patients received a median of 11 treatment cycles (range = 1-16); more than three-quarters (n=22; 79%) received maintenance therapy with daratumumab after completing six treatment cycles.
The study’s primary endpoint was overall complete hematologic response rate, assessed according to international amyloidosis consensus criteria and evaluated every four weeks during cycles 1 through 6 and every month thereafter.
All but one patient (n=27; 96%) responded to treatment with daratumumab plus CyBorD. Most responders achieved at least a very good partial response (VGPR; 82%), with 10 achieving a CR.
Responses appeared to happen within the first treatment cycle, at a median of 23 days after treatment initiation (range not reported). The median times to CR and VGPR were 85 days (range = 29-226 days) and 22 days (range = 7-228 days), respectively.
The one patient whose disease did not respond to treatment eventually experienced disease progression while on the study. However, “all 10 patients who achieved a CR continue to respond to treatment,” Dr. Comenzo reported, and the median duration of CR had not been reached.
Six participants went on to receive subsequent autologous hematopoietic cell transplantation; four of these patients have died (2 due to disease progression and 2 due to events following transplant).
The investigators also noted that the daratumumab combination had “a well-tolerated safety profile.” The most common treatment-related adverse events (AEs) included diarrhea (64%), fatigue (50%), and peripheral edema (50%). “Two patients (7%) experienced infusion-related reactions, all of which were grade 1,” the researchers added.
The results of this portion of the study are limited by the small patient population. The findings also will need to be compared with the CyBorD-alone arm of the ANDROMEDA study, which the authors noted is continuing to enroll patients.
The authors report relationships with Janssen, which sponsored this trial.
Comenzo RL, Kastritis E, Maurer M, et al. Subcutaneous daratumumab + cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients with newly diagnosed amyloid light chain (AL) amyloidosis: updated safety run-in results of ANDROMEDA. Abstract #S875. Presented at the 24th European Hematology Association Annual Congress, June 15, 2019; Amsterdam, The Netherlands.