ABSTRACT
The combination of pomalidomide and low-dose dexamethasone (Pom-Dex) can be safely administered to patients with end-stage relapsed/refractory multiple myeloma (RRMM). However, we observed a shorter median progression-free survival (PFS) and overall survival (OS) in these patients when characterized with adverse cytogenetics (deletion 17p and translocation [4;14]) in the Intergroupe Francophone Myélome (IFM) 2009-02 trial. We then sought to determine whether MM with adverse cytogenetics would benefit more from Pom-Dex if exposed earlier in the multicenter IFM 2010-02 trial. The intention-to-treat population included 50 patients, with a median age of 63 years (38% were ≥65 years). Interestingly, there was a striking difference in time to progression (TTP), duration of response, and overall response rate (ORR) according to the presence of del(17p) compared with t(4;14) (TTP, 7.3 vs 2.8 months; duration of response, 8.3 vs 2.4 months; and ORR, 32% vs 15%). OS was prolonged after Pom-Dex, particularly in t(4;14), given the short TTP, suggesting that patients were rescued at relapse with further lines of therapy. Pom-Dex, a doublet immunomodulatory drug-based regimen, is active and well tolerated in adverse cytogenetic patients with early RRMM, particularly in those with del(17p), who are characterized by a high and rapid development of a refractoriness state and known for their poor prognosis. Future studies will determine the underlying mechanisms of Pom-Dex activity in del(17p). This trial is registered at www.clinicaltrials.gov as #NCT01745640.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chromosomes, Human, Pair 14/genetics , Chromosomes, Human, Pair 17/genetics , Chromosomes, Human, Pair 4/genetics , Gene Deletion , Multiple Myeloma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Translocation, Genetic/genetics , Adult , Aged , Aged, 80 and over , Dexamethasone/administration & dosage , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm/drug effects , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multiple Myeloma/genetics , Multiple Myeloma/mortality , Multiple Myeloma/pathology , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Survival Rate , Thalidomide/administration & dosage , Thalidomide/analogs & derivativesABSTRACT
INTRODUCTION: Disseminated intravascular coagulation (DIC) is a rare event in acute lymphoblastic leukemia (ALL). However, it has been described in a few cases of pre-B ALL with translocation t(17;19)(q22;p13) which results in the fusion of E2A gene with sequences of HLF gene. Here, we report a case of pre-B ALL with DIC and an apparently normal karyotype by R banding. MATERIALS AND METHODS: Fluorescent in situ hybridization (FISH) studies were performed on bone marrow cells from the patient at presentation and after three months of therapy. RT-PCR was used to detect the E2A-HLF transcript. The type of rearrangement was characterized by sequencing. RESULTS: The t(17;19)(q22;p13) was detected by FISH analysis. The fusion E2A-HLF was amplified by RT-PCR and sequenced, giving a type I rearrangement with a long insertion (146 nucleotides) between E2A exon 13 and HLF exon 4. CONCLUSION: While translocation t(17;19) is undetectable by R-banding technique, it can be detected with FISH and amplified with RT-PCR. Therefore, systematic molecular investigations should be conducted for all patients with pre-B ALL associated with DIC, in order to appreciate the incidence and the prognostic value of this rare abnormality.
