In the past 20 years, few diseases have seen as great progress in their treatment as multiple myeloma. With the approval of many new drugs and the limited availability of clinical trials comparing head-to-head the different possible combinations, the choice of the best treatments at each stage of the disease becomes complex as well as crucial since multiple myeloma remains incurable. This article presents a general description of the novelties of the whole treatment of multiple myeloma, from induction in the newly diagnosed patient through the role of hematopoietic stem cell transplantation and maintenance treatment until early and late relapses, including a section on recently approved drugs as well as novel drugs and immunotherapy in advanced stages of research, and that will surely play a relevant role in the treatment of this devastating disease in the coming years.

Between 20-40% of patients with multiple myeloma (MM) present with renal impairment (RI) at diagnosis (Korbet & Schwartz, 2006; Kastritis et al., 2007) and up to 10% of them require dialysis (Dimopoulos et al., 2010). Prognosis in these patients remains significantly worse when compared with patients with normal renal function (Haynes et al., 2010). Daratumumab is an anti-CD38 IgG kappa human monoclonal antibody that has demonstrated superior clinical benefit across lines of therapy, either as monotherapy or when combined with standard-of-care regimens for the treatment of patients with relapsed and refractory MM (RRMM) (Usmani et al., 2016; van de Donk et al., 2016). However, data of daratumumab in patients with RRMM and dialysis-dependant renal failure are lacking. We report the efficacy and safety results from a retrospective Spanish study of daratumumab in patients with RRMM and end-stage RI requiring dialysis. Methods M.J.C. performed the research and contributed to analyzing of data and paper writing. J.D.L.R. was involved in designing the study, analysis, interpretation and reporting of the data, and wrote/reviewed the paper. All authors performed the research and reviewed the draft manuscript and approved the final version for publication.

IntroductionInv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) is a rare poor prognosis cytogenetic abnormality present in acute myeloid leukemia (AML) and other myeloid neoplasms.ObjectiveThe aim of this study was to evaluate the outcome of a cohort of 61 patients with newly diagnosed AML with inv(3)/t(3;3) treated with homogeneous intensive chemotherapy protocols conducted by the Spanish PETHEMA and CETLAM cooperative groups between 1999 and 2017.MethodsIn this retrospective study the main clinical and biologic parameters were collected. The complete response (CR) rate, the cumulative incidence of relapse (CIR) and the overall survival (OS) were calculated. An analysis of prognostic factors for survival was performed.ResultsSixty‐one patients received induction and only 18 (29%) achieved CR (median age, 46 years). Allogeneic hematopoietic stem cell transplantation (alloHSCT) was performed in 36 patients (59%), 15 with active disease. One‐ and 4‐year CIR were 52% and 56%. One‐ and 4‐year OS probabilities were 41% and 13%. By multivariate analysis monosomal karyotype (MK) was associated with poorer OS (HR 2.0, P = .017).ConclusionInv(3)/t(3;3) AML is a poor prognosis entity with low response to standard chemotherapy and to alloHSCT because of frequent and early relapse. MK was associated with a poorer prognosis. Improved therapeutic strategies are clearly needed.

response by R-CHOP or R-CVP. Rituximab maintenance (single infusion for four weeks every six months for maximum of two years) was given to 169 patients (77%) with median duration of 1.6 years.Results: Baseline characteristics are following: aged >60 was 105 (47%), men was 92 (42%), stage III/IV was 174 (79%), nodal lesions > four sites was 118 (54%), grade 3a was 33 (15), bone marrow involvement was 84 (40%), elevated LDH was 36 (16%), hemoglobin <12 g/dl was 27 (12%), bulky disease (tumor diameter > 6 cm) was 43 (20%), β2MG > 2 mg/dl was 83 (37%), and SUV max > 10 was 48 (22%). FLIPI classified patients into 99 (45%) as low FLIPI, 55 (25%) as intermediate FLIPI, and 66 (30%) as high FLIPI, respectively. FLIPI2 classified patients into 40 (18%) as low FLIPI2, 130 (59%) as intermediate FLIPI2, and 50 (23%) as high FLIPI2, respectively. Pretreatment sIL-2R (median 871 IU/ml, range 115-13700) was significant higher in patients, who experienced a relapse. ROC curve illustrates 1070 IU/ml as adequate cut-off value to predict relapse of FL in this cohort (AUC = 0.7, 95%CI = 0.62-0.78). Elevated LDH, stage III/IV, involved nodal sites >4, bone marrow involvement, bulky disease, elevated β2MG, SUVmax >10 in PET scan, high FLIPI, and high FLIPI2 were statistically associated with high sIL-2R, respectively. At the median follow-up time of 74.2 months, the six-year PFS was 75.1% (95% CI = 66.5-81.8) in the maintenance + group versus 44.1% (95%CI = 28.5-58.6) in the maintenance group (P < 0.0000001) and 84.0% (95%CI = 74.4-90.2) in the low sIL-2R group versus 51.1% (95%CI = 39.8-61.3) in the high sIL-2R groups, respectively (P < 0.000001). The six-year PFS was 84.8%, 78.4%, 58.5%, and 48.1% in the maintenance+/low sIL-2R, maintenance-/low sIL-2R, maintenance+/high sIL-2R, and maintenance-/high sIL-2R groups, respectively (P < 0.000001). Multivariate analysis showed that high sIL-2R (hazard ratio 2.7, 95% confidential interval = 1.3-5.6, P < 0.01) was an independent factor of poor PFS as well as elevated β2MG and no rituximab maintenance.Conclusions: Pretreatment high sIL-2R level was an independent poorprognostic factor and also a surrogate marker of the presence of aggressive component in FL in this cohort. Univariate and multiple Cox regression models were used to assess the effect of covariates on PFS and OS. KeywordsResults: Median (range) age at diagnosis was 62 years (32-83).Forty-eight percent of patients had high-risk FLIPI and 36.7% were high-risk FLIPI-2. Patient characteristics are shown in the Table 1.The most commonly front-line therapies administered were R-CHOP (56.9%) and R-CVP (40%). Rituximab maintenance was administered to 48 patients (73.8%). Overall, 67.2% of patients achieved complete remission (CR) and 12.5% partial remission (PR) with no significant differences between both regimens. Conclusions:Our results show that refractoriness to chemoimmunotherapy and early progression after treatment were the most relevant variables affecting outcome of patients. Both factors should be used to stratify th...