PD-L1/PD-1 presence in the tumor microenvironment and activity of PD-1 blockade in multiple myeloma

Paiva, Bruno; Azpilikueta, Arantza; Puig, Noemí; Ocio, Enrique M.; Sharma, Rajni; Oyajobi, Babatunde O.; Labiano, Sara; San-Segundo, Laura; Rodriguez, Anthony B.; Aires-Mejía, Irene; Rodríguez, Ismael; Escalante, Fernando; Coca, Alfonso García de; Bárez, Abelardo; Miguel, Jesús F. San; Melero, Ignacio

doi:10.1038/leu.2015.79

Cited by 170 publications

(172 citation statements)

References 15 publications

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“…27,28,30 This basic postulate is not that clear as the authors differ in their results, and it can be also true that PD-L1 is truly overexpressed only on PCs from MRD positive samples. 32 Analogically, discordant results have been reported about the immune effector cell population responsible for killing PCs. G€ org€ un et al highlighted the higher cytotoxic capacity of NK cells and Ray et al considered the most effective CD8 C T cells together with NK cells.…”

Section: Resultsmentioning

confidence: 79%

“…33 Finally, Paiva et al found a similar percentage of PD-1 C T cells between controls and newly diagnosed MM and MGUS, but they confirmed a significant increase in PD-1 expression on both CD4 C and CD8 C T cells in samples from MRD positive MM and relapsing MM patients. 32 …”

Section: Expression Of Pd-1 On T Cellsmentioning

confidence: 99%

“…35 In the third study, Paiva et al used anti-PD-1 mAb alone and also demonstrated significantly superior survival in the treatment cohort. 32 …”

Section: Murine Modelsmentioning

confidence: 99%

“…If we consider the fact that PD-L1 expression on malignant cells is higher only in MRD positive patients, 32 then perhaps this is the correct time to start the treatment. Another approach is to administer PD-1/PD-L1 inhibitors during the lymphodepletion period after autologous stem cell transplantation, when the immune system is recovering.…”

Section: Future Directionsmentioning

confidence: 99%

“…Benson et al and G€ org€ un et al confirmed a significantly higher expression on NK cells from MM patients compare with HD, whereas Paiva et al did not find any difference between them. 30,32,34 Preclinical data…”

Section: Expression Of Pd-1 On Nk Cellsmentioning

confidence: 99%

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PD-1/PD-L1 inhibitors in multiple myeloma: The present and the future

Jelı́nek

2016

OncoImmunology

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The introduction of PD-1/PD-L1 pathway inhibitors has marked a significant milestone in the treatment of various types of solid tumors. The current situation in multiple myeloma (MM) is rather unclear, as distinct research groups have reported discordant results. This discrepancy dominantly concerns the expression of PD-1/PD-L1 molecules as well as the identification of the responsible immune effector cell population. The results of monotherapy with PD-1/PD-L1 inhibitors have been unsatisfactory in MM, suggesting that a combination approach is needed. The most logical partners are immunomodulatory agents as they possess many synergistic effects. We are also proposing other rational and promising combinations (e.g., daratumumab, ibrutinib, anti-CD137) that warrant further investigation.

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Section: Resultsmentioning

confidence: 79%

Section: Expression Of Pd-1 On T Cellsmentioning

confidence: 99%

“…35 In the third study, Paiva et al used anti-PD-1 mAb alone and also demonstrated significantly superior survival in the treatment cohort. 32 …”

Section: Murine Modelsmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

Section: Expression Of Pd-1 On Nk Cellsmentioning

confidence: 99%

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PD-1/PD-L1 inhibitors in multiple myeloma: The present and the future

Jelı́nek

2016

OncoImmunology

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Plasma Cell Tumors

Hideshima

Anderson

2017

Holland‐Frei Cancer Medicine

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Overview Plasma cell disorders have in common a proliferation of monoclonal plasma cells associated with the production of a monoclonal protein. These disorders range from the common, indolent condition of monoclonal gammopathy of undetermined significance to malignancies, such as multiple myeloma, characterized by the presence of hypercalcemia, anemia, renal dysfunction, and/or lytic lesions. Progress in the understanding of the molecular underpinnings of myeloma has led to remarkable advances in its treatment. High‐dose melphalan with autologous stem‐cell transplant was historically a mainstay of treatment. Now, highly effective and well‐tolerated drug classes such as the proteasome inhibitors (e.g., bortezomib and carfilzomib) and immunomodulatory drugs (e.g., lenalidomide and pomalidomide) have rapidly transformed the treatment of myeloma and significantly improved the overall survival. The increasing use of extended treatment strategies such as maintenance therapy and the arrival of newer drug classes such as plasma cell‐specific monoclonal antibodies are setting the stage for improving outcomes further.

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