Daratumumab, bortezomib, melphalan, and prednisone versus bortezomib, melphalan, and prednisone alone in transplant-ineligible Asian patients with newly diagnosed multiple myeloma: final analysis of the phase 3 OCTANS Study.

The superiority and tolerability of daratumumab plus bortezomib/melphalan/prednisone (D-VMP) versus bortezomib/melphalan/prednisone (VMP) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) was previously described in the global phase 3 ALCYONE study. The primary analysis of the phase 3 OCTANS study further demonstrated the superiority and tolerability of D-VMP (n = 144) versus VMP (n = 71) in transplant-ineligible Asian patients with NDMM. The current analysis describes the final efficacy and safety outcomes for D-VMP versus VMP in OCTANS, with a follow-up of > 3 years.

Prognostic factors in 448 newly diagnosed multiple myeloma receiving bortezomib-based induction: impact of ASCT, transplant refusal and high-risk MM.

In Hong Kong, newly diagnosed multiple myeloma (NDMM) receives bortezomib-based triplet induction. Upfront autologous stem cell transplant (ASCT) is offered to transplant eligible (TE) patients (NDMM ≤ 65 years of age), unless medically unfit (TE-unfit) or refused (TE-refused). Data was retrieved for 448 patients to assess outcomes.

Bortezomib, Melphalan, and Prednisone With or Without Daratumumab in Transplant-ineligible Asian Patients With Newly Diagnosed Multiple Myeloma: The Phase 3 OCTANS Study.

Introduction: In the global phase 3 ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) improved outcomes versus VMP in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Here, we report the primary analysis of the phase 3 OCTANS trial of D-VMP versus VMP in transplant-ineligible Asian NDMM patients.

Patients And Methods: In total, 220 patients were randomized (2:1) to receive 9 cycles of VMP (bortezomib 1.

The impact of bortezomib-based induction in newly diagnosed multiple myeloma with chromosome 1q21 gain.

Introduction: Bortezomib has been reported to favourably impact the outcomes of (4;14) and del(17p) in multiple myeloma (MM), but its impact on gain 1q (+1q) is unknown.

Methods: To address this, 250 patients treated with bortezomib-based induction were analysed. All myeloma samples had fluorescence hybridization (FISH) performed on CD138-sorted bone marrow aspirate, and plasma cells were analysed using DNA probes specific for the following chromosomal aberrations: del(13q14), del(17p), (14;16), (4;14), and +1q.

Epigenetic Silencing of Tumor Suppressor lncRNA : Implication on NF-κB Signaling in Non-Hodgkin's Lymphoma.

The long non-coding RNA (lncRNA) localized to 20q13.31, is a negative regulator of NF-κB signaling implicated in carcinogenesis. As a CpG island is embedded in the promoter region of , it is hypothesized as a tumor suppressor lncRNA silenced by promoter DNA methylation in non-Hodgkin's lymphoma (NHL).

Case series: MRD negativity assessment using C-Acetate PET with 3-weekly daratumumab-based quadruplet induction in newly diagnosed multiple myeloma.

Complete response (CR) is an important favorable factor for survival in multiple myeloma (MM). However, CR patients continue to relapse, especially in the presence of minimal residual disease (MRD). Bone marrow (BM) MRD is predictive of progression-free survival (PFS) in MM.

3-weekly daratumumab-lenalidomide/pomalidomide-dexamethasone is highly effective in relapsed and refractory multiple myeloma.

Objectives: Myeloma relapse remains challenging. Daratumumab (dara) with immunomodulatory agents (IMiD) and dexamethasone (dex) was proven highly effective in relapsed or refractory multiple myeloma (RRMM) in randomized controlled trials. The recommended schedule of dara is weekly for eight doses, followed by 2-weekly for eight doses, and then every 4-weekly thereafter.

miR-1250-5p is a novel tumor suppressive intronic miRNA hypermethylated in non-Hodgkin's lymphoma: novel targets with impact on ERK signaling and cell migration.

Background: miR-1250 is localised to the second intron of AATK at chromosome 17q25. As a CpG island is present at the putative promoter region of its host gene, AATK, we postulated that the intronic miR-1250-5p is a tumor suppressor miRNA co-regulated with its host gene, AATK, by promoter DNA methylation in non-Hodgkin's lymphoma (NHL).

Methods: AATK/miR-1250 methylation was studied in healthy controls, including ten normal peripheral blood buffy coats and eleven normal tonsils, ten lymphoma cell lines, and 120 primary lymphoma samples by methylation-specific PCR (MSP).

A proof-of-concept study for the pathogenetic role of enhancer hypomethylation of MYBPHL in multiple myeloma.

Enhancer DNA methylation and expression of MYBPHL was studied in multiple myeloma (MM). By bisulfite genomic sequencing, among the three CpGs inside the MYBPHL enhancer, CpG1 was significantly hypomethylated in MM cell lines (6.7-50.

Minimal Residual Disease Detection by Next-Generation Sequencing in Multiple Myeloma: A Comparison With Real-Time Quantitative PCR.

Here we compared clonotype identification by allele-specific oligonucleotide real-time quantitative-PCR (ASO RQ-PCR) and next-generation sequencing (NGS) in 80 multiple myeloma patients. ASO RQ-PCR was applicable in 49/55 (89%) and NGS in 62/78 (80%). Clonotypes identified by both methods were identical in 33/35 (94%).

Epigenetic silencing of miR-342-3p in B cell lymphoma and its impact on autophagy.

Background: miR-342-3p, localized to 14q32, is a tumor suppressor miRNA implicated in carcinogenesis. Given the presence of a promotor-associated CpG island for its host gene, EVL, we hypothesized that intronic miR-342-3p is a tumor suppressor co-regulated with host gene by promoter DNA methylation in B cell lymphoma.

Results: By bisulfite pyrosequencing-verified methylation-specific PCR (MSP), EVL/MIR342 methylation was detected in five (50%) lymphoma cell lines but not normal peripheral blood and tonsils.

Epigenetic silencing of long non-coding RNA in multiple myeloma: impact on prognosis and myeloma dissemination.

Background: Long non-coding RNA (lncRNA) is a tumor suppressor in gastric cancer and chronic lymphocytic leukemia. As the promoter and coding region of are fully embedded in a CpG island, we hypothesized that is a tumor suppressor lncRNA epigenetically silenced by promoter DNA methylation in multiple myeloma.

Methods: Methylation-specific PCR and quantitative bisulfite pyrosequencing were performed to detect the methylation of in normal plasma cells, myeloma cell lines and primary myeloma samples.

Low-dose pembrolizumab and nivolumab were efficacious and safe in relapsed and refractory classical Hodgkin lymphoma: Experience in a resource-constrained setting.

The efficacy and safety of low-dose anti-PD1 antibodies in relapsed/refractory classical Hodgkin lymphoma (cHL) require confirmation. Pembrolizumab (100 mg every 3 weeks, Q3W) or nivolumab (40 mg Q2W) were administered to patients with relapsed/refractory cHL. In the pembrolizumab cohort (N = 11), who had failed a median of three (1-6) therapies (brentuximab vedotin [BV]: 91%; autologous hematopoietic stem cell transplantation [auto-HSCT]: 18%), the overall response rate (ORR) by positron emission tomography-computed tomography was 100% (metabolic complete response [mCR]: 73%; partial response [PR]: 27%).

Primary refractory multiple myeloma: a real-world experience with 85 cases.

This study determined whether 85 patients with multiple myeloma (MM) double-refractory to primary induction therapy with triplet regimens had a homogenous prognosis. The overall response rate (ORR) after the second-line therapy was 51%. Patients who proceeded to immediate autologous stem cell transplantation (ASCT) had better ORR than those who received conventional therapies (62% vs.

Pomalidomide and dexamethasone combination with additional cyclophosphamide in relapsed/refractory multiple myeloma (AMN001)-a trial by the Asian Myeloma Network.

Pomalidomide is a third generation immunomodulatory drug which in combination with dexamethasone, has been shown to be active in relapsed/refractory multiple myeloma. However, the data in Asian patients remain limited. We conducted a prospective phase two clinical trial in major cancer centers in Singapore, South Korea, Taiwan, Japan and Hong Kong to assess the efficacy and safety of pomalidomide and dexamethasone combination (PomDex) +/- cyclophosphamide in Asian patients with relapsed/refractory multiple myeloma who failed lenalidomide and bortezomib.

Ficolled bone marrow is superior to bone marrow buffy coat for detection of minimal residual disease in multiple myeloma.

Objective: Buffy coat and ficoll of bone marrow (BM) are viable options for the study of minimal residual disease (MRD) in multiple myeloma (MM). As yet, there is no data about the superiority of either sample types. Herein, we aimed to address this issue.

Standardized Minimal Residual Disease Detection by Next-Generation Sequencing in Multiple Myeloma.

Next-generation sequencing (NGS) has been applied to monitor minimal residual disease (MRD) in multiple myeloma (MM). Standardized DNA input and sequencing depth is essential for achieving a uniform sensitivity in NGS-based MRD study. Herein, the sensitivity of 10 was verified by a standardized experimental design based on triplicate measurements of 1 μg DNA input and 1 million sequencing reads using the LymphoTrack-MiSeq platform.

Epigenetic silencing of miR-340-5p in multiple myeloma: mechanisms and prognostic impact.

Background: miR-340-5p, localized to 5q35, is a tumor suppressor miRNA implicated in multiple cancers. As a CpG island is present at the putative promoter region of its host gene, RNF130, we hypothesized that the intronic miR-340-5p is a tumor suppressor miRNA epigenetically silenced by promoter DNA methylation of its host gene in multiple myeloma.

Results: By pyrosequencing-confirmed methylation-specific PCR, RNF130/miR-340 was methylated in 8/15 (53.

Survival differences in multiple myeloma in Latin America and Asia: a comparison involving 3664 patients from regional registries.

In previous observational studies, we have separately characterized patients with multiple myeloma (MM) both from Latin America (LA) and from Asia. Here, we analyze these two datasets jointly, in order to assess the overall survival (OS) in these two world regions. Data were available from 3664 patients (1968 from LA and 1696 from Asia); all of whom diagnosed between 1998 and 2007.

Distinct promoter methylation profile reveals spatial epigenetic heterogeneity in 2 myeloma patients with multifocal extramedullary relapses.

Spatial and subclonal genetic heterogeneity in multiple myeloma (MM) have been demonstrated by sequencing of plasma cells from multi-focal regions, but studies of spatial epigenetic heterogeneity are scanty. Herein, promoter methylation status of genes implicated in disease progression (CDKN2A and SHP1) and marrow escape (CDH1, CD56, and CXCR4) was studied in two patients with multi-focal extramedullary relapses. Patient 1 developed simultaneous chest wall and duodenal plasmacytoma at relapse.

Frequent functional activation of RAS signalling not explained by RAS/RAF mutations in relapsed/refractory multiple myeloma.

RAS mutations are frequent in relapsed/refractory multiple myeloma (RRMM) but functional study in primary samples is scanty. Herein, in primary myeloma plasma cells of 17 suspected RRMM, functional activation of RAS signalling was studied by Western blot of phosphorylated ERK1/2 (phospho-ERK1/2). Moreover, activating mutations in KRAS, NRAS, BRAF, and ALK were studied by PCR and bidirectional direct sequencing.

Recent advances in the management of multiple myeloma: clinical impact based on resource-stratification. Consensus statement of the Asian Myeloma Network at the 16th international myeloma workshop.

Predicated on our improved understanding of the disease biology, we have seen remarkable advances in the management of multiple myeloma over the past few years. Recently approved drugs have radically transformed the treatment paradigm and improved survivals of myeloma patients. The progress has necessitated revision of the diagnostic criteria, risk-stratification and response definition.