Immune status of high-risk smoldering multiple myeloma patients and its therapeutic modulation under LenDex: a longitudinal analysis

Paiva, Bruno; Mateos, María Victoria; Sánchez‐Abarca, Luis Ignacio; Puig, Noemí; Vidriales, María‐Belén; López-Corral, Lucía; Corchete, Luis A.; Hernández, Miguel T.; Bargay, Joan; Arriba, Felipe de; Rubia, Javier de la; Teruel, Ana-Isabel; Giraldo, Pilar; Rosiñol, Laura; Prósper, Felipe; Oriol, Albert; Hernández, José; Esteves, Graça; Lahuerta, Juan José; Bladé, Joan; Pérez-Simón, José A.; Miguel, Jesús F. San

doi:10.1182/blood-2015-10-662320

Cited by 65 publications

(64 citation statements)

References 56 publications

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“…Similarly, Pomalidomide (Pomalyst™) has been approved by FDA in 2013 due to its anti-tumor properties characterized by increasing NK cell activation, down-regulating osteoclastogenesis and inhibiting the interaction between stromal and myeloma cells [96, 97, 101]. The introduction of Lenalidomide (CC-5013, Revlimid ® ) as new clinical approach improved the median survival of MM patients, even in those developing resistance and disease relapse [102–105]. Following its approval in 2006 by FDA in MM treatment, a plethora of clinical trials registered in www.clinicaltrials.gov demonstrated a strong anti-tumor effect of Lenalidomide when administrated alone or combined with others drugs [22, 102, 103, 106–108].…”

Section: Lenalidomide As Promising Strategy To Restore Immune Responsmentioning

confidence: 99%

Activation of NK cells and disruption of PD-L1/PD-1 axis: two different ways for lenalidomide to block myeloma progression

2017

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Section: Lenalidomide As Promising Strategy To Restore Immune Responsmentioning

confidence: 99%

Activation of NK cells and disruption of PD-L1/PD-1 axis: two different ways for lenalidomide to block myeloma progression

2017

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“…The role of immune system impairment in the risk of progression to MM has also been suggested by Paiva et al suggesting that high risk SMM patients have an impaired immune system. (20) Also, treatment with immunomodulators such as lenalidomide results in therapeutic immunomodulation associated with marked increases in functional T-lymphocytes and NK-cells to delay the progression to MM. (20) Nevertheless, only the presence of either any cPCs or just ≥ 150 cPCs were independent predictors of progression of SMM to MM within two years of cPC assessment in multivariable models that included both (i/u) FLC ratio > 8 and the presence of immunoparesis.…”

Section: Discussionmentioning

confidence: 99%

Quantification of circulating clonal plasma cells via multiparametric flow cytometry identifies patients with smoldering multiple myeloma at high risk of progression

et al. 2016

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The presence of high numbers of circulating clonal plasma cells (cPCs) in patients with smoldering multiple myeloma (SMM), detected by a slide-based immunofluorescence assay, has been associated with a shorter time to progression (TTP) to multiple myeloma (MM). The significance of quantifying cPCs via multiparameter flow cytometry, a much more readily available diagnostic modality, in patients with SMM has not been evaluated. This study evaluated 100 patients with a known or new diagnosis of SMM who were seen at the Mayo Clinic, Rochester from January 2008 until December 2013. Patients with ≥ 150 cPCs (N = 9) were considered to have high number of cPCs based on the 97% specificity and 78% PPV of progression to MM within 2 years of cPC assessment. The median TTP of patients with ≥ 150 cPCs was 9 months compared to not reached for patients with < 150 cPCs (P < 0.001). Thus, quantification of cPCs via multiparametric flow cytometry identifies patients with SMM at very high risk of progression to MM within 2 years and warrants confirmation in larger studies. In the future, this may allow reclassification of such patients as having MM requiring therapy prior to them enduring end-organ damage.

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“…IMiDs have the dual effects of direct tumoricidal activity and immunomodulation, which improve immune function [24]. In high-risk smoldering MM patients, who have already exhibited impaired immune systems, lenalidomide/dexamethasone (Rd) was able to restore decreased expression of activation and type 1 T-helper proliferation markers and induced a marked shift in T cells and natural killer (NK) cells [25]. It was reported that the fold change in the number of regulatory T cells (Tregs) in peripheral blood was significantly higher in relapsed MM patients compared with patients who achieved a complete response (CR) 1 year after auto-SCT transplantation [26].…”

Section: Imid-intensified Antibody Treatmentmentioning

confidence: 99%

Immunotherapy for Multiple Myeloma

Tamura

Ishibashi

Sunakawa

et al. 2019

Cancers

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Despite therapeutic advances over the past decades, multiple myeloma (MM) remains a largely incurable disease with poor prognosis in high-risk patients, and thus new treatment strategies are needed to achieve treatment breakthroughs. MM represents various forms of impaired immune surveillance characterized by not only disrupted antibody production but also immune dysfunction of T, natural killer cells, and dendritic cells, although immunotherapeutic interventions such as allogeneic stem-cell transplantation and dendritic cell-based tumor vaccines were reported to prolong survival in limited populations of MM patients. Recently, epoch-making immunotherapies, i.e., immunomodulatory drug-intensified monoclonal antibodies, such as daratumumab combined with lenalidomide and chimeric antigen receptor T-cell therapy targeting B-cell maturation antigen, have been developed, and was shown to improve prognosis even in advanced-stage MM patients. Clinical trials using other antibody-based treatments, such as antibody drug-conjugate and bispecific antigen-directed CD3 T-cell engager targeting, are ongoing. The manipulation of anergic T-cells by checkpoint inhibitors, including an anti-T-cell immunoglobulin and ITIM domains (TIGIT) antibody, also has the potential to prolong survival times. Those new treatments or their combination will improve prognosis and possibly point toward a cure for MM.

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Immune status of high-risk smoldering multiple myeloma patients and its therapeutic modulation under LenDex: a longitudinal analysis

Abstract: Key Points High-risk SMM patients’ immune status is mildly impaired as compared with age-matched healthy individuals. High-risk SMM patients can be effectively immunomodulated by lenalidomide, even when combined with low-dose dexamethasone.

Cited by 65 publications

References 56 publications

Activation of NK cells and disruption of PD-L1/PD-1 axis: two different ways for lenalidomide to block myeloma progression

Activation of NK cells and disruption of PD-L1/PD-1 axis: two different ways for lenalidomide to block myeloma progression

Quantification of circulating clonal plasma cells via multiparametric flow cytometry identifies patients with smoldering multiple myeloma at high risk of progression

Immunotherapy for Multiple Myeloma

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