Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster II
Hematology Disease Topics & Pathways:
antibodies, Biological, Diseases, Therapies, immunotherapy, Plasma Cell Disorders, Lymphoid Malignancies
All patients were treated in the Department of Clinical Therapeutics, Athens, Greece. The study included patients who had achieved either PR or VGPR after completing standard bortezomib-based primary therapy. Consolidation included 4 weekly infusions of daratumumab 16 mg/kg. Pre-emptive therapy for IRR was given starting two days before the first infusion of daratumumab that included low dose steroids (equivalent of 16 mg of methylprednisolone), H1 & H2 inhibitors and montelukast.
Twenty-five patients (20 with AL and 5 with LCDD) received daratumumab consolidation. Among patients with AL amyloidosis, median age is 65, kidneys and heart were involved in 70% and 75% respectively, baseline Mayo stage was 20%, 70% and 10% for stage 1,2 & 3 respectively. Baseline immunofixation in serum or urine was positive in all patients, median baseline dFLC at diagnosis was 125 mg/L (range 60-7228). Median time from start of first line therapy to daratumumab consolidation was 7 months and all patients had completed their planned therapy. At the time of initiation of daratumumab, 24 patients were in VGPR and one in PR and the median dFLC level was 12 mg/L; all had positive serum or urine immunofixation and in all patients MRD was detectable by NGF-MFC. Except for one patient, all the others received the planned 4 daratumumab infusion. Mild IRRs occurred in 3 patients (grade 1 in 2 and grade 2 in one patient); no IRRs occurred after the first infusion.
One month after completion of consolidation with daratumumab, median dFLC dropped to 5 mg/L and 10 (40%) of the patients improved their response: 36% from VGPR to hemCR and one patient with PR to VGPR. Among those that achieved a hemCR, 5 (50%) became MRD negative by NGF-MFC. However, even among those that remained MRD-positive there was a decrease in the number of aberrant plasma cells (APCs) by a median of one log. In MRD-positive patients a change in the composition of the remaining phenotypic subclones of APCs was also observed. Regarding the other BM cell populations, we observed statistically significant changes in B-cell precursors (increased from 14.32%+/-11.75% to 34.76% +/-24.11%, p=0.0004), naïve B-cells (decreased from 65.58%+/-17.56% to 47.37%+/-22.66%, p=0.0003), T cells (increased from 6.44% +/- 2.78% to 10.86%+/- 6.407%, p=0.0007), CD27+ NK & NKT cells (increased from 15.65% +/-13.5% to 36.34%+/- 24.43%, p=0.0002), mast cells (increased from 0.0092%+/-0.0123% to 0.011%+/-0.012%, p=0.002) and erythroblasts (increased from 1.82%+/-0.97% to 2.41%+/- 1.03%, p=0.076). Due to the small numbers it was not possible to make meaningful comparison between MRD positive and negative patients. However, the above results indicate that even a short course of daratumumab was able to cause significant changes in the BM microenvironment of these patients. From this small prospective study we conclude that consolidation with a short course of daratumumab can improve the depth of response in patients with AL or LCDD that have not achieved a hemCR after primary therapy, even to the depth of undetected MRD. In addition, daratumumab causes significant changes in the BM environment, which need further investigation in order to understand their implications.
Disclosures: Kastritis: Genesis Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Gavriatopoulou: Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Terpos: BMS: Honoraria; Celgene: Honoraria; Takeda: Honoraria, Other: travel expenses , Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Genesis pharma SA: Honoraria, Other: travel expenses , Research Funding; Sanofi: Honoraria. Dimopoulos: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau.
OffLabel Disclosure: daratumumab for AL amyloidosis
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