Type: Oral
Session: 652. Multiple Myeloma and Plasma Cell Dyscrasias: Clinical and Epidemiological: Prognostic Factors in Newly Diagnosed Multiple Myeloma (NDMM)
Hematology Disease Topics & Pathways:
Research, Clinical Research, Plasma Cell Disorders, Diseases, Lymphoid Malignancies, Biological Processes, Technology and Procedures, multi-systemic interactions, Study Population, Human, Minimal Residual Disease
The presence of CPCs was prospectively evaluated in 114 consecutive patients with AL amyloidosis who were diagnosed and treated in the Department of Clinical Therapeutics, Athens, Greece. CPCs were assessed in peripheral blood (PB) according to the Euroflow guidelines, using two independent 8-color panels, both containing CD19-PC7, CD27-BV510, CD38-FITC, CD45-PerCPCy5.5, CD56-PE, CD138-BV421, and additionally CD117-APC and CD81-APCC750 only in the surface tube or CyIgκ-APC and CyIgλ-APCC750 only in the intracytoplasmic tube. A median number of 5 million events (range 3.9x106-6.1x106) were acquired for each tube and median sensitivity level was 2.3x10-6 (range 2-3.1x10-6)
The median age of the cohort was 67 years (38-87), 57% were males, 86% had cardiac, 56% renal, 34% soft tissue, 24% PNS and 19% liver involvement. Mayo stage distribution was 13%, 33% and 54% for stages 1, 2 & 3 and renal stage was 20%, 57% & 23% for stages 1, 2 & 3 respectively. Median iFLC and dFLC levels were 299.3 and 288.5 mg/L respectively and median BM infiltration was 10% (range 0-60%). By FISH, 46% had t(11;14), 40% del13q, 29% +1q21, 6% del17p, 2% t(4;14) and 4% t(14;16). Treatment was bortezomib-based in 96% and contained daratumumab in 34%.
CPCs were detectable in 64% of patients and their median level in those with detectable CPCs was 0.002% (range 0.0001%-11.4%). Patients with detectable CPCs had higher LDH (p=0.003), iFLCs (p=0.029), BM infiltration (p=0.002) and NTproBNP (p=0.009). Among patients with detectable CPCs, there was also a correlation of their levels with iFLC levels (p<0.001) and BM infiltration (p<0.001). CPCs were more often detectable (81.5% vs 60%, p=0.053) and their levels were also higher (p=0.014) in those with +1q21; there was no association with any other cytogenetic abnormality.
Median follow up of the cohort is 2 years. There was no difference in the OS (2-year OS 65% vs 63%) or in early mortality for patients with or without detectable CPCs (p=0.965). Due to the high sensitivity of NGF in the detection of CPCs, we also evaluated different cutoffs of CPCs for their possible prognostic impact, including cutoffs proposed in the earlier study and in patients with newly diagnosed symptomatic MM (0.01%), but we found no prognostic impact on OS in our patients with AL amyloidosis (2-year OS:55% vs 66%, p=0.374). Higher BM infiltration has been associated with worse outcome in patients with AL amyloidosis: in bivariate analysis CPCs>0.01% overcame the prognostic impact of higher BM infiltration, indicating that CPCs is a more sensitive biomarker of tumor burden in patients with AL amyloidosis. Even after adjustment for Mayo stage the presence of CPCs or of CPCs >0.01% were not prognostically significant. However, patients with CPCs>0.01% had a lower probability of hematologic CR/VGPR at 1 month (23% vs 56%, p=0.03) and at 3 months (44% vs 76%, p=0.043) from start of therapy.
In conclusion, circulating clonal plasma cells can be detected in the majority of patients with AL amyloidosis with more sensitive NGF methods. Their presence is associated with higher FLC levels and BM infiltration and adverse prognostic features such as higher NTproBNP level, and a lower probability of deep hematologic response at 1 and 3 months after start of therapy. However, in the era of modern therapies, CPCs do not seem to independently affect the prognosis of patients with AL amyloidosis, which is dominated by the degree of cardiac dysfunction.
Disclosures: Kastritis: GSK: Honoraria; Takeda: Honoraria; Pfizer: Honoraria, Research Funding; Genesis Pharma: Honoraria; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Terpos: BMS: Honoraria; EUSA Pharma: Honoraria, Other: Travel expenses; Genesis: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria; Takeda: Honoraria, Other: Travel expenses, Research Funding; Sanofi: Honoraria, Research Funding; Amgen: Honoraria, Other: Travel expenses, Research Funding. Dimopoulos: BMS: Honoraria; Beigene: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria.
See more of: Oral and Poster Abstracts