Multiple myeloma, immunotherapy and minimal residual disease

Ning

et al. 2019

WJCC

BACKGROUNDThe guiding effect of prognostic stratification in multiple myeloma (MM) for treatment has been increasingly emphasized in recent years. The stratification of risk factors based on the International Staging System (ISS), Durie-Salmon (DS) staging and related indicators is affected by the renal function of patients, resulting in poor performance. This study assesses the relationship between interleukin-32 (IL-32) and related risk factors in 67 patients with MM and their clinical outcomes.AIMTo investigate the feasibility of IL-32 in evaluating prognosis in patients with MM and the factors influencing prognosis.METHODSThis was a pragmatic, prospective observational study of patients with MM at a single center. According to IL-32 level, patients were divided into two groups. The variables under consideration included age, blood β2-microglobulin, albumin, C-reactive protein, serum calcium, serum creatinine, lactate dehydrogenase, M protein type, ISS stage, DS stage, and IL-32 levels and minimal residual disease (MRD) after induction treatment. The main outcomes were progression-free survival (PFS) and overall survival (OS).RESULTSIL-32 was an important factor affecting PFS and OS in patients with MM. Compared with patients with IL-32 levels ≥ 856.4 pg/mL, patients with IL-32 levels < 856.4 pg/mL had longer PFS (P = 0.0387) and OS (P = 0.0379); Univariate analysis showed that IL-32 level and MRD were significantly associated with OS and PFS (P < 0.05). Multivariate analysis showed that IL-32 levels ≥ 856.4 pg/mL and MRD positive were still independent risk factors for OS and PFS (P < 0.05).CONCLUSIONIL-32 is valuable for assessing the prognosis of MM patients. IL-32 level combined with MRD may be a useful routine evaluation index for MM patients after treatment.

Section: Introductionmentioning

confidence: 99%

Expression of interleukin-32 in bone marrow of patients with myeloma and its prognostic significance

Ning

et al. 2019

WJCC

“…Given the success of targeted immunotherapy with monoclonal antibodies in other cancers, recent research has focused on the development of this class of drugs for multiple myeloma [4][5].…”

mentioning

confidence: 99%

Real-world effectiveness and safety of daratumumab, bortezomib and dexamethasone in relapsed/refractory multiple myeloma in Slovakia

Harvanova¹,

Štulajterová²,

Guman³

et al. 2021

neo

Real-world data on regimens for relapsed/refractory multiple myeloma (RRMM) are limited. Daratumumab in combination with bortezomib and dexamethasone is a promising new treatment. The aim of this analysis was to assess the outcomes of daratumumab-bortezomib-dexamethasone (DVd) combination for the treatment of patients with RRMM in a real-world setting. All consecutive RRMM patients who received at least two cycles of DVd treatment between December 2016 and July 2020 were identified. We analyzed the clinical characteristics and survival of 47 patients treated at 7 Slovak centers outside of the clinical trials. The median age was 65 years (range, 35 to 83). The median (range) number of lines of therapy per patient was 3 (2-6). All patients were previously exposed to PIs (proteasome inhibitors) and IMIDs (immunomodulatory drugs), the majority of patients (70.2%) had double refractory (IMIDs and PI) disease and 72.3% of patients were refractory to their last therapy. Most patients presented with high-risk characteristics, including 25.6% adverse cytogenetics and 25.5% extramedullary disease. The majority of patients responded with an overall response rate of 78%, we found complete response in 3, very good partial response in 22, partial response in 12, minor response or stable disease in 9, and progressive disease in 1 patient. After a median follow-up period of 8 months, the median progression-free survival was 10 months. There was a longer progression-free survival in those with 2 vs. > 2 prior treatments, with equally good effectivity in standard risk and high-risk cytogenetic groups. The adverse events were usually mild, none leading to permanent drug interruptions. Daratumumab-bortezomib-based combinations are efficacious and safe regimens in RRMM patients in the real-world setting. This is the first analysis in Slovakia addressing the DVd combination outside of the clinical trial setting.

“…It is estimated that approximately 30,280 cases of myeloma are expected to be diagnosed in 2017 and almost 12,590 myeloma patients will die from the disease [2]. While autologous stem cell transplantation (ASCT) and high-dose chemotherapy have recently improved the overall survival of MM patients [3,4], the minimal or measurable residual disease (MRD) followed by ASCT and the inevitable drug resistance to chemotherapeutic drugs are still major causes of MM progression and relapse [5,6]. Therefore, cancer immunotherapy capable of killing multi-drug-resistant malignant cells and stabilizing or even clearing the MRD should be an effective strategy for patients with relapsed/ refractory MM [7,8].…”

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confidence: 99%

Carfilzomib combined with ex vivo-expanded patient autologous natural killer cells for myeloma immunotherapy

Chang

Hou

Chen

et al. 2018

neo

Natural killer (NK) cell-based immunotherapy is promising, as NK cells are in the first line of defense against cancer and capital of lysing tumor cells without pre-stimulation. However, NK cells from multiple myeloma (MM) patients are always deficient in numbers and the expression of certain activating receptors, disabling them in cytotoxicity against the cancer. Therefore, effective strategies to expand NK cells and increase NK cell-mediated cytotoxicity against MM are significant. Here, NK cells were efficiently expanded from peripheral blood mononuclear cells (PBMCs) of newly diagnosed MM patients after co-culture with irradiated K562 cells transfected with 41BBL and membrane-bound interleukin (IL)-15 (K562-mb15-41BBL) in the presence of 200 IU/ml human IL-2. The ex vivo-expanded NK cells were demonstrated to vigorously kill both MM cells and autologous primary MM cells without significant lysis of patient normal cells. Further exploration revealed a significant increase in cell surface expression of most activating receptors of NK cells and indicated that expanded NK (exp-NK) cell killing of MM cells was mediated by perforin/granzyme. NK cells are capital of lysing human leukocyte antigen (HLA) I-deficient tumor cells and carfizomib, a selective proteasome inhibitor approved for the treatment of relapsed/refractory MM patient, down-regulates the expression of HLA class I, thus enhancing NK cell-mediated lysis in MM. Here, we found for the first time that carfizomib dramatically augmented ex vivo exp-NK cell cytotoxicity against patient autologous MM cells, suggesting the use of exp-NK alone or in combination with the drug to treat MM patient.