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Abstract Recommendations regarding the best time to start treatment in patients with relapsed/refractory multiple myeloma (RRMM) after biological relapse/progression (BR) are unclear. This observational, prospective, multicenter registry aimed to evaluate the impact on time to progression (TTP) of treatment initiation at BR versus at symptomatic clinical relapse (ClinR) based on the Spanish routine practice in adult patients with RRMM. Patients had two or less previous treatment lines and at least one previous partial response. Baseline characteristics and treatment outcomes were recorded, and survival was analyzed. Of 225 patients, 110 were treated at BR (TxBR group) and 115 at ClinR (TxClinR group) according to the investigators' criteria. The proportion of patients with higher ECOG, previous noncomplete remission (CR), and second relapse were significantly higher in the TxBR group compared to the TxClinR group. TheTxClinR group showed improved outcomes, including TTP, compared to the TxBR group. Progression‐free survival increased in the TxClinR group (56.2 months) compared to the TxBR group (32.5 months) (p = 0.0137), and median overall survival also increased (p = 0.0897). Median TTP was significantly longer in patients relapsing from a CR (50.4 months) and in their first relapse (38.7 months) compared to those relapsing from a non‐CR response (32.9 months) and in their second relapse (25.2 months). Physicians seemed to start treatment earlier in RRMM patients with poor prognosis features. Previous responses to anti‐MM treatment and the number of prior treatment lines were identified as prognosis factors, whereby relapse from CR and first relapse were associated with a longer time to progression.

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Despite recent progress in the therapeutic approach of malignant hemopathies, their prognoses remain frequently poor. Immunotherapy could open a new window of great interest in this setting. Natural killer (NK) cells constitute an important area of research for hematologic malignancies, because this subpopulation is able to kill target cells spontaneously without previous sensitization, representing a novel tool in the treatment of them. Abnormal NK cytolytic function is observed in several hematological malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndromes. Several mechanisms are involved in this abnormal function, such as decreased expression of activating receptors, increased expression of inhibitory receptors or defective expression of NK cell ligands on target cells. New immunotherapies are focused in identifying factors that could increase the expression of these activating receptors, to counteract inhibitory receptors expression, and therefore, to improve the NK cell cytotoxic capacities against tumor cells. In this work, we analyze the effect of interleukin (IL)-15 on the expression of NK cell-activating receptors that play a crucial role in the lysis of blasts from AML patients. Our results showed that IL-15 increased the surface expression of NKp30 on NK cells from healthy donors and AML patients with the consequent improvement of NK cell cytotoxicity. Besides, the upregulation of NKp30 induced by IL-15 is associated with an improvement of NK-mediated myeloid dendritic cells (DCs) maturation. NK cells cultured with IL-15 showed an upregulation of NKp30, which is associated with an increase anti-tumor activity and with an improved maturation of immature DCs. In our in vitro model, IL-15 exerted a great activating stimulus that could be used as novel immunotherapy in AML patients.