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Immunomodulatory Drugs in the Context of Autologous Hematopoietic Stem Cell Transplantation Associate With Reduced Pro-tumor T Cell Subsets in Multiple Myeloma.

ABSTRACT: Immunomodulatory drugs (IMiDs) are effective therapeutics for multiple myeloma (MM), where in different clinical settings they exert their function both directly on MM cells and indirectly by modulating immune cell subsets, although with not completely defined mechanisms. Here we studied the role of IMiDs in the context of autologous hematopoietic stem cell transplantation on the T cell subset distribution in the bone marrow of newly diagnosed MM patients. We found that after transplantation pro-tumor Th17-Th1 and Th22 cells and their related cytokines were lower in patients treated with IMiDs during induction chemotherapy compared to untreated patients. Of note, lower levels of IL-17, IL-22, and related IL-6, TNF-?, IL-1?, and IL-23 in the bone marrow sera correlated with treatment with IMiDs and favorable clinical outcome. Collectively, our results suggest a novel anti-inflammatory role for IMiDs in MM.

SUBMITTER: Di Lullo G

PROVIDER: S-EPMC6348257 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Immunomodulatory Drugs in the Context of Autologous Hematopoietic Stem Cell Transplantation Associate With Reduced Pro-tumor T Cell Subsets in Multiple Myeloma.

Di Lullo Giulia G Marcatti Magda M Heltai Silvia S Tresoldi Cristina C Paganoni Anna Maria AM Bordignon Claudio C Ciceri Fabio F Protti Maria Pia MP

Frontiers in immunology 20190121

Immunomodulatory drugs (IMiDs) are effective therapeutics for multiple myeloma (MM), where in different clinical settings they exert their function both directly on MM cells and indirectly by modulating immune cell subsets, although with not completely defined mechanisms. Here we studied the role of IMiDs in the context of autologous hematopoietic stem cell transplantation on the T cell subset distribution in the bone marrow of newly diagnosed MM patients. We found that after transplantation pro ...[more]

PMID: 30719025

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Project description:Autologous hematopoietic stem cell transplantation (AHCT) improves survival in patients with multiple myeloma (MM) but is associated with morbidity and nonrelapse mortality (NRM). Hematopoietic cell transplant comorbidity index (HCT-CI) was shown to predict risk of NRM and survival after allogeneic transplantation. We tested the utility of HCT-CI as a predictor of NRM and survival in patients with MM undergoing AHCT. We analyzed outcomes of 1156 patients of AHCT after high-dose melphalan reported to the Center for International Blood and Marrow Transplant Research. Individual comorbidities were prospectively collected at the time of AHCT. The impact of HCT-CI and other potential prognostic factors, including Karnofsky performance score (KPS), on NRM and survival were studied in multivariate Cox regression models. HCT-CI score was 0, 1, 2, 3, and >3 in 42%, 18%, 13%, 13%, and 14% of the study cohort, respectively. Subjects were stratified into 3 risk groups: HCT-CI score of 0 (42%) versus HCT-CI score of 1 to 2 (32%) versus HCT-CI score > 2 (26%). Higher HCT-CI was associated with lower KPS < 90 (33% of subjects score of 0 versus 50% in HCT-CI score > 2). HCT-CI score > 2 was associated with melphalan dose reduction (22% versus 10% in score 0 cohort). One-year NRM was low at 2% (95% confidence interval, 1% to 4%) and did not correlate with HCT-CI score (P = .9). On multivariate analysis, overall survival was inferior in groups with HCT-CI score of 1 to 2 (relative risk, 1.37, [95% confidence interval, 1.01 to 1.87], P = .04) and HCT-CI score > 2 (relative risk, 1.5 [95% confidence interval, 1.09 to 2.08], P = .01). Overall survival was also inferior with KPS < 90 (P < .001), IgA subtype (P ≤ .001), those receiving >1 pretransplant induction regimen (P = .007), and those with resistant disease at the time of AHCT (P < .001). AHCT for MM is associated with low NRM, and death is predominantly related to disease progression. Although a higher HCT-CI score did not predict NRM, it was associated with inferior survival.

Project description:BACKGROUND:Immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide; IMID) are widely used in the treatment of multiple myeloma patients. To date, few data are available on IMID adherence in multiple myeloma patients. The aim of our study was to evaluate IMID adherence and to compare two indirect methods to measure IMID adherence in multiple myeloma patients: a specific questionnaire and the medication possession ratio (MPR). Another aim was to explore this specific questionnaire for the assessment of IMID adherence in multiple myeloma patients. METHODS:All consecutive multiple myeloma patients, with at least two consecutive dispensations of thalidomide, lenalidomide or pomalidomide in our hospital were included in this prospective study. IMID adherence was measured using a specific questionnaire and the medication possession ratio. Relationship between the questionnaire scores and variables of interest was evaluated by multiple linear regression with a robust variance estimator. FINDINGS:Sixty-three patients were included in our study. The mean questionnaire score was 8.2±1.2 and the mean medication possession ratio value was 0.97±0.06. A total of 76% of patients were considered adherent according to the questionnaire (i.e. score ≥ 8), 94% according to the medication possession ratio (i.e. MPR ≥ 0.90), and 70% according to the questionnaire and the medication possession ratio. No statistically significant linear association was observed between the questionnaire score and any variables of interest including medication possession ratio. All Cronbach's alpha were relatively low (range 0.0342-0.2443), showing a low correlation of the different questions with the questionnaire score. CONCLUSIONS:Our study is the first prospective study evaluating IMID adherence in multiple myeloma patients in real life. The high adherence to IMIDs reported here, regardless of the drug, is encouraging considering the efficacy, toxicity and elevated cost of IMIDs. The specific questionnaire should be used with caution to evaluate IMID adherence.

Dataset Information

Immunomodulatory Drugs in the Context of Autologous Hematopoietic Stem Cell Transplantation Associate With Reduced Pro-tumor T Cell Subsets in Multiple Myeloma.

Publications

Immunomodulatory Drugs in the Context of Autologous Hematopoietic Stem Cell Transplantation Associate With Reduced Pro-tumor T Cell Subsets in Multiple Myeloma.

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