ABSTRACT
BACKGROUND: Even in the era of novel immunotherapies for multiple myeloma (MM), treatment of late-stage relapsed/refractory (RR) patients remains challenging. The aim of our study was to analyze the efficacy and safety of the five-drug combination pomalidomide, bortezomib, doxorubicin, dexamethasone, and daratumumab ("Pom-PAD-Dara") in RRMM. METHODS: We retrospectively analyzed data of 56 patients with RRMM who received Pom-PAD-Dara between September 2016 and May 2019. RESULTS: Patients were heavily pretreated with a median of four prior lines of therapy, including autologous and allogenic stem cell transplant in 50 (89%) and six (11%) patients, respectively. The overall response rate (ORR) was 78% and we observed partial remission, very good partial remission, and complete remission in 27 (48%), 13 (23%) and four (7%) patients, respectively. Median progression-free survival was 7 months (95% CI, 3.3-10.7) and the median overall survival was not reached at 24 months. Adverse events grade ≥ 3 were observed 41 (73%) patients and included neutropenia (n = 28, 50%), anemia (n = 22, 39%), thrombocytopenia (n = 21, 38%), and pneumonia (n = 6, 11%). CONCLUSION: Pom-PAD-Dara represents a promising multiagent regimen in heavily pretreated RRMM patients with high ORR and an acceptable safety profile.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Multiple Myeloma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adult , Aged , Aged, 80 and over , Anemia/chemically induced , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bortezomib/administration & dosage , Bortezomib/adverse effects , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Drug Administration Schedule , Female , Humans , Induction Chemotherapy , Leukopenia/chemically induced , Male , Middle Aged , Multiple Myeloma/mortality , Multiple Myeloma/surgery , Neoplasm Recurrence, Local/mortality , Neutropenia/chemically induced , Pneumonia/chemically induced , Progression-Free Survival , Retrospective Studies , Stem Cell Transplantation , Thalidomide/administration & dosage , Thalidomide/adverse effects , Thalidomide/analogs & derivatives , Thrombocytopenia/chemically induced , Treatment OutcomeSubject(s)
Gene Expression Regulation, Neoplastic/drug effects , Lymphoma , Multiple Myeloma , Neoplasm Proteins/biosynthesis , Peptides/administration & dosage , Positron-Emission Tomography , Receptors, CXCR4/biosynthesis , Adult , Aged , Female , Humans , Lymphoma/diagnostic imaging , Lymphoma/radiotherapy , Male , Middle Aged , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/radiotherapy , Neoplasm Proteins/agonists , Receptors, CXCR4/agonistsSubject(s)
Databases, Nucleic Acid , Multiple Myeloma/genetics , Multiple Myeloma/mortality , Neoplasm Proteins/genetics , Aged , Aged, 80 and over , DNA Mutational Analysis , Disease-Free Survival , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Multiple Myeloma/pathology , Survival RateSubject(s)
Biomarkers, Tumor/metabolism , Carbon Radioisotopes/metabolism , Methionine/metabolism , Multiple Myeloma , Positron-Emission Tomography , Tomography, X-Ray Computed , Aged , Female , Humans , Male , Middle Aged , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/metabolism , Multiple Myeloma/pathology , Prospective StudiesABSTRACT
We constructed a multiple myeloma (MM)-specific gene panel for targeted sequencing and investigated 72 untreated high-risk (del17p) MM patients. Mutations were identified in 78% of the patients. While the majority of studied genes were mutated at similar frequency to published literature, the prevalence of TP53 mutation was increased (28%) and no mutations were found in FAM46C. This study provides a comprehensive insight into the mutational landscape of del17p high-risk MM. Additionally, our work demonstrates the practical use of a customized sequencing panel, as an easy, cheap and fast approach to characterize the mutational profile of MM.
