Search results for "Multiple myeloma."

Identification of residues in the putative 5th helical region of human interleukin-6, important for activation of the IL-6 signal transducer, gp130

1996

AbstractWe have previously shown that L58 in the putative 5th helical region of human interleukin-6 (IL-6) is important for activation of the IL-6 signal transducer gp130 [de Hon et al. (1995) FEBS Lett. 369, 187–191]. To further explore the importance of individual residues in this region for gp130 activation we have now combined Ala substitutions of residues E52, S53, S54, K55, E56, L58 and E60 with other substitutions in IL-6, known to affect gp130 activation (Q160E and T163P). The combination mutant protein with L58A completely lost the capacity to induce the proliferation of XG-1 myeloma cells, and could effectively antagonize wild type IL-6 activity on these cells. Moreover, the data …

EVALUATION AND POTENTIAL ROLE OF BONE MARROW TISSUE-RESIDENT MEMORY T-CELLS IN PATIENTS WITH PLASMA CELL DYSCRASIAS

2020

DARATUMUMAB, BORTEZOMIB AND DEXAMETHASONE (DVD) VS BORTEZOMIB AND DEXAMETHASONE (VD) IN RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM): EFFICACY AND …

2017

8036 Background: Daratumumab (D), a human, CD38-targeting mAb, is well tolerated and induces deep and durable responses in patients (pts) with RRMM. We provide an update of CASTOR (NCT02136134), a multicenter, phase 3, randomized study of DVd vs Vd in RRMM. Methods: All pts received ≥1 prior line of therapy (LOT) and were administered 8 cycles (Q3W) of Vd (1.3 mg/m2 SC bortezomib on days 1, 4, 8, and 11; 20 mg PO/IV dexamethasone on days 1-2, 4-5, 8-9, and 11-12) ± D (16 mg/kg IV once weekly in Cycles 1-3, every 3 weeks for Cycles 4-8, then every 4 weeks until progression). Bortezomib-refractory pts were ineligible. Minimal residual disease (MRD) was assessed upon suspected CR and at 6 and…

Deep MRD profiling defines outcome and unveils different modes of treatment resistance in standard- and high-risk myeloma

2021

PETHEMA/GEM Cooperative Group.

Health-related quality of life maintained over time in patients with relapsed or refractory multiple myeloma treated with daratumumab in combination …

2020

In the phase III CASTOR trial, daratumumab, bortezomib and dexamethasone (D-Vd) significantly extended progression-free survival compared with bortezomib and dexamethasone (Vd) alone in patients with relapsed/refractory multiple myeloma (RRMM). Here, we present patient-reported outcomes (PROs) from the CASTOR trial. PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system questionnaire. Treatment effects through Cycle 8 were measured by a repeated measures mixed-effects model. After Cycle 8, PROs were only collected for patients in the D-Vd group who con…

Role of pamidronate disodium in the treatment of metastatic bone disease.

1998

Aims and Background Bone metastases are a common feature of advanced neoplastic disease and are considered to be among the most frequent causes of pain and complications in oncologic patients. The main objective of the treatment of such patients is to control their symptoms and improve their quality of life. Pamidronate disodium is a second-generation bisphosphonate capable of inhibiting bone resorption (particularly osteoclast activity) without affecting bone reminerali-zation. After a brief introduction concerning the pathophysiology of bone metastases and neoplastic bone pain, we herein present data on the clinical pharmacology and toxicity of bisphosphonates in general, and pamidronate …

Treatment of Lenalidomide Exposed or Refractory Multiple Myeloma: Network Meta-Analysis of Lenalidomide-Sparing Regimens.

2021

Over the past 10 years, the treatment of multiple myeloma (MM) dramatically changed due to the introduction of a number of new agents and combination regimens both in the frontline and in the relapsed/refractory setting. Currently, at least 11 classes of therapeutic agents, including steroids, alkylators (melphalan and cyclophosphamide), proteasome inhibitors (PI: bortezomib, carfilzomib, ixazomib), immunomodulatory agents (thalidomide, lenalidomide, pomalidomide), monoclonal antibodies (mAbs: elotuzumab, daratumumab), HDAC-inhibitors (panobinostat), BCL2 inhibitors (venetoclax), selective inhibitors of nuclear export (selinexor), drug-conjugated mAbs (belantamab mafodotin), bispecific agen…

Efficacy and safety of daratumumab, bortezomib, and dexamethasone (D-Vd) in relapsed or refractory multiple myeloma (RRMM) based on cytogenetic risk:…

2019

8040 Background: MM patients (pts) with high cytogenetic risk have poor outcomes. In CASTOR, D-Vd prolonged progression-free survival (PFS) vs bortezomib and dexamethasone (Vd) alone, and exhibited tolerability in RRMM pts. We conducted a subgroup analysis of D-Vd vs Vd in CASTOR, based on cytogenetic risk. Methods: Pts received ≥1 prior line of therapy. Cytogenetic risk was based on a combined analysis of next-generation sequencing (NGS) and fluorescence in situ hybridization/karyotype testing. High-risk pts had t(4;14), t(14;16), or del17p abnormalities. Standard (std)-risk pts were confirmed negative for all 3 abnormalities. Minimal residual disease (MRD; 10–5) was assessed via NGS usin…

Updated results from BELLINI, a phase III study of venetoclax or placebo in combination with bortezomib and dexamethasone in relapsed/refractory mult…

2020

8509 Background: Venetoclax (Ven) is a selective, potent, oral BCL-2 inhibitor. In the Phase 3 BELLINI trial, addition of Ven to bortezomib (B) + dexamethasone (d) significantly improved response rates and progression-free survival (PFS) vs placebo (Pbo) and showed significant efficacy in patients (pts) with either t(11;14) or BCL2high gene expression. Here we present updated safety and efficacy data from the prespecified second interim overall survival (OS) analysis. Methods: In this multicenter, randomized, double-blind study (NCT02755597), pts with relapsed/refractory multiple myeloma (RRMM) with 1-3 prior lines of therapy were randomized 2:1 to Ven (800 mg) or Pbo in combination with B…

Analysis of treatment efficacy in the GEM-CESAR trial for high-risk smoldering multiple myeloma patients: Comparison between the standard and IMWG MR…

2020

8512 Background: The GEM-CESAR trial is a potentially curative strategy for high-risk smoldering multiple myeloma (HRsMM) patients (pts) in which the primary endpoint is the achievement of sustained minimal residual disease (MRD) negativity in the bone marrow (BM) by next generation flow (NGF). The value of BM MRD assessment in MM is proven, but alternative, non-invasive methods, accurately reflecting disease burden are needed. Methods: Pts received six 4-week cycles of KRd as induction (K:36mg/m2 twice weekly, R: lenalidomide 25mg po od days 1-21 and d:dexamethasone 40mg po weekly) followed by melphalan 200mg/m2, two further cycles of KRd as consolidation and up to 2 years of Rd (R:10mg/d…