A Novel RUNX1 Genetic Variant Identified in a Young Male with Severe Osteoporosis.

This case describes a young man with an unusual cause of severe osteoporosis and markedly deranged bone microarchitecture resulting in multiple fractures. A potentially pathogenic germline variant in the runt-related transcription factor 1 (RUNX1) gene was discovered by a focused 51-gene myeloid malignancy panel during investigation for his unexplained normochromic normocytic anemia. Further bone-specific genetic testing and a pedigree analysis were declined by the patient.

A sequential cohort study evaluating single-agent KappaMab and KappaMab combined with lenalidomide and low-dose dexamethasone in relapsed and/or refractory kappa light chain-restricted multiple myeloma (AMaRC 01-16).

KappaMab (KM; formerly MDX-1097) is a monoclonal antibody specific for the kappa myeloma antigen (KMA), a cell-surface antigen expressed on malignant plasma cells in kappa-restricted multiple myeloma (κMM), some lymphomas, occasional tonsillar B cells and in vitro activated B cells, but not on normal B cells in bone marrow. Phase I/IIa studies of single-agent KM confirmed a favourable toxicity profile and evidence of anti-myeloma activity. Ex-vivo studies demonstrating upregulation of KMA by lenalidomide, and enhanced effector-cell cytotoxicity provided the rationale for this phase IIb study where KM or KM in combination with lenalidomide and dexamethasone (KM-Rd) was administered in relapsed, refractory κMM patients.

Response adaptive salvage with KTd and ASCT for functional high-risk multiple myeloma-The Australasian Leukemia and Lymphoma Group (ALLG) MM17 Trial.

We evaluated re-induction incorporating carfilzomib-thalidomide-dexamethasone (KTd) and autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM) refractory, or demonstrating a suboptimal response, to non-IMID bortezomib-based induction. KTd salvage consisted of thalidomide 100 mg daily and dexamethasone 20 mg orally combined with carfilzomib 56 mg/m days 1, 2, 8, 9, 15 and 16, of each 28-day cycle. Following four cycles, patients achieving a stringent complete response proceeded to ASCT whereas those who did not received a further two cycles then ASCT.

Upfront tandem autologous non-myeloablative allogeneic stem cell transplant in high-risk multiple myeloma: a long-term single-centre experience.

The role of upfront non-myeloablative allogeneic stem cell transplantation (NMA alloSCT) in high-risk multiple myeloma (HR-MM) is unclear. We evaluated outcomes of NMA alloSCT following autologous stem cell transplant (ASCT) compared with ASCT alone for newly diagnosed HR-MM. Two-year progression-free survival was improved in the ASCT-NMA alloSCT group (44% vs 16%; P = 0.

The Utility of Euroflow MRD Assessment in Real-World Multiple Myeloma Practice.

Measurable residual disease (MRD) is being recognised as an optimal method for assessing depth of response, identifying higher risk of relapse, and guiding response-based treatment paradigms for multiple myeloma (MM). Although MRD negativity is increasingly replacing complete response as the surrogate endpoint in clinical trials, its role in real-world practice is less established. We retrospectively analyzed EuroFlow MRD results from patients with newly diagnosed MM (NDMM) who underwent bortezomib, cyclophosphamide and dexamethasone (VCD) induction and high dose melphalan conditioned autologous stem cell transplant (ASCT) at the Alfred Hospital between January 2016 and December 2020.

Imaging of patients with multiple myeloma and associated plasma cell disorders: consensus practice statement by the Medical Scientific Advisory Group to Myeloma Australia.

Imaging modalities for multiple myeloma (MM) have evolved to enable earlier detection of disease. Furthermore, the diagnosis of MM requiring therapy has recently changed to include disease prior to bone destruction, specifically the detection of focal bone lesions. Focal lesions are early, abnormal areas in the bone marrow, which may signal the development of subsequent lytic lesions that typically occur within the next 18-24 months.

Cereblon pathway biomarkers and immune profiles in patients with myeloma receiving post-ASCT lenalidomide maintenance (LEOPARD).

LEOPARD was a single arm, phase II study of lenalidomide (LEN) and alternate day prednisolone maintenance in patients with newly diagnosed multiple myeloma (MM) following autologous stem cell transplantation (ASCT). Sixty patients were enrolled. Estimated median potential follow-up was 44 m, median PFS was 38.

A phase II trial of continuous ixazomib, thalidomide and dexamethasone for relapsed and/or refractory multiple myeloma: the Australasian Myeloma Research Consortium (AMaRC) 16-02 trial.

We evaluated the efficacy and tolerability of continuous ixazomib-thalidomide-dexamethasone (ITd: 4 mg, day 1, 8, 15; 100 mg daily; and 40 mg weekly). A total of 39 patients with relapsed/refractory multiple myeloma (RRMM) aged ≥18 years with one to three prior lines of therapy were enrolled from two tertiary centres in Victoria and South Australia, Australia. The overall response rate (ORR) was 56·4% with a clinical benefit rate of 71·8%.

Evaluation of EuroFlow minimal residual disease measurement and donor chimerism monitoring following tandem auto-allogeneic transplantation for multiple myeloma.

Prognostic factors for multiple myeloma (MM) after allogeneic haemopoietic stem cell transplantation (alloHSCT) are poorly characterised. Two potential factors include minimal residual disease (MRD) and CD3 donor-specific chimerism. We retrospectively examined 93 consecutive patients who received upfront or deferred tandem auto-alloHSCT.

Phase II trial of single-agent panobinostat consolidation improves responses after sub-optimal transplant outcomes in multiple myeloma.

Panobinostat is a pan-deacetylase inhibitor that modulates the expression of oncogenic and immune-mediating genes involved in tumour cell growth and survival. We evaluated panobinostat-induced post-transplant responses and identified correlative biomarkers in patients with multiple myeloma who had failed to achieve a complete response after autologous transplantation. Patients received panobinostat 45 mg administered three-times weekly (TIW) on alternate weeks of 28-day cycles commencing 8-12 weeks post-transplant.

Oral azacitidine (CC-486) in combination with lenalidomide and dexamethasone in advanced, lenalidomide-refractory multiple myeloma (ROAR study).

In preclinical studies, oral azacitidine (CC-486), a hypomethylating agent, has been shown to have a direct anti-MM effect and in vitro anti-MM synergism when combined with lenalidomide (LEN). We present a phase 1b, single center, 3 × 3 dose escalation study with planned expansion at maximum tolerated dose (MTD), which assessed the safety and efficacy of combining CC-486 with LEN (25 mg d1-21/28) and dexamethasone (DEX) (40 mg weekly) in patients with relapsed/refractory MM who had previously failed LEN. Twenty-four patients were enrolled.

Monitoring tumour burden and therapeutic response through analysis of circulating tumour DNA and extracellular RNA in multiple myeloma patients.

Monitoring tumour burden and therapeutic response through analyses of circulating cell-free tumour DNA (ctDNA) and extracellular RNA (exRNA) in multiple myeloma (MM) patients were performed in a Phase Ib trial of 24 relapsed/refractory patients receiving oral azacitidine in combination with lenalidomide and dexamethasone. Mutational characterisation of paired BM and PL samples at study entry identified that patients with a higher number of mutations or a higher mutational fractional abundance in PL had significantly shorter overall survival (OS) (p = 0.005 and p = 0.

Phase 3 study of subcutaneous bortezomib, thalidomide, and prednisolone consolidation after subcutaneous bortezomib-based induction and autologous stem cell transplantation in patients with previously untreated multiple myeloma: the VCAT study.

Efficacy and safety of bortezomib-based consolidation following ASCT were investigated in newly diagnosed multiple myeloma patients from Australia, Korea, and China. Patients received three cycles of bortezomib-cyclophosphamide-dexamethasone induction followed by high-dose therapy/ASCT, then were randomized (1:1) to consolidation with TP (thalidomide 100 mg/d for ≤12 months/until disease progression; prednisolone 50 mg on alternate days indefinitely/until disease progression;  = 100) or VTP (subcutaneous bortezomib 1.3 mg/m every 2 weeks for 32 weeks, plus TP;  = 103).

Idiopathic systemic capillary leak syndrome presenting as septic shock: A case report.

Background: Idiopathic capillary leak syndrome (Clarkson's Disease) is a rare angiopathy with a heterogenous phenotype that may present as distributive shock refractory to resuscitative management.

Objective: We report a case of idiopathic systemic capillary leak syndrome presenting as septic shock.

Methods: Structured case report and review of the literature.

DCEP as a bridge to ongoing therapies for advanced relapsed and/or refractory multiple myeloma.

There is limited data describing dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) in relapsed refractory multiple myeloma (RRMM). We reviewed 65 patients with RRMM receiving DCEP between 2005 and 2017 in two Melbourne Hospitals. Patients had received a mean of three prior treatment lines (range, 1-11).

Bisphosphonate guidelines for treatment and prevention of myeloma bone disease.

Multiple myeloma (MM) is a haematological malignancy characterised by the clonal proliferation of plasma cells in the bone marrow. More than 80% of patients with MM display evidence of myeloma bone disease (MBD), characterised by the formation of osteolytic lesions throughout the axial and appendicular skeleton. MBD significantly increases the risk of skeletal-related events such as pathologic fracture, spinal cord compression and hypercalcaemia.

Adverse impact of high donor CD3+ cell dose on outcome following tandem auto-NMA allogeneic transplantation for high-risk myeloma.

High-risk (HR) multiple myeloma (MM) has poor outcomes with conventional therapy. Tandem autologous-non-myeloablative (NMA) allogeneic stem cell transplantation (autologous stem cell transplantation (ASCT)-NMA allogeneic SCT) is potentially curative secondary to graft-versus-myeloma effect. We retrospectively analysed ASCT-NMA allogeneic SCT outcomes of 59 HR and relapsed MM patients.

Treatment of patients with Waldenström macroglobulinaemia: clinical practice guidelines from the Myeloma Foundation of Australia Medical and Scientific Advisory Group.

Waldenström macroglobulinaemia (WM) is an indolent B-cell malignancy characterised by the presence of immunoglobulin M (IgM) paraprotein and bone marrow infiltration by clonal small B lymphocytes, plasmacytoid lymphocytes and plasma cells. The symptoms of WM are protean, often follow an asymptomatic phase and may include complications related to the paraneoplastic effects of IgM paraprotein. The revised 2016 World Health Organization classification includes the MYD88 L265P mutation, which is seen in >90% of cases, within the diagnostic criteria for WM.