Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.
This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.
Chimeric antigen receptor (CAR) T-cell therapy has emerged as an option for relapsed/refractory aggressive B-cell lymphomas that have failed 2 lines of therapy. Failures usually occur early after infusion. The purpose of our study was to identify factors that may predict failure, particularly early progression (EP), within the first month after infusion. Characteristics of 116 patients were analyzed at the time of decision (TD) to use commercial CAR (axicabtagene ciloleucel, n = 49; tisagenlecleucel n = 67) and at the time of treatment (TT), together with total metabolic tumor volume (TMTV) at TT. With a median follow-up of 8.2 months, 55 patients failed treatment; 27 (49%) were early progressors. The estimated 12-month progression-free survival (PFS) and overall survival (OS) were 47.2% (95% confidence interval [CI], 38.0-58.6) and 67.0% (95% CI, 57-79), respectively. Univariate analyses for PFS and OS identified Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage III/IV disease, extranodal (EN) sites ≥2, elevated lactate dehydrogenase (LDH), increased C-reactive protein (CRP), high International Prognostic Index at TD and at TT, as well as increased CRP, bulky mass, and high TMTV at TT, as risk factors. Multivariate analyses for PFS, EP, and OS identified elevated LDH and EN sites ≥2 at TD and the same predictors at TT (ie, increased CRP, EN sites ≥2, and TMTV >80 mL). In summary, risk factors identified for early progression at TD and at TT were EN involvement (≥2 sites) and lymphoma burden (LDH, TMTV).
IntroductionChronic myelomonocytic leukemia (CMML), which is the most frequent myelodysplastic/myeloproliferative disorder, 1 is characterized by the accumulation of monocytes and a variable proportion of immature dysplastic granulocytes in the PB and the BM. 2 Clonal cytogenetic abnormalities are detected in ϳ 40%, 3 and a copyneutral uniparental disomy in leukemic cells of ϳ 50% of the patients. 4 Mutations in ASXL1, TET2, and RUNX1 genes are detected in 25% to 50% of patients, RAS and CBL gene mutations in 10% to 25% of patients, and mutations in JAK2, FLT3, LNK, UTX, EZH2, IDH1, and IDH2 in Ͻ 10% of patients. 5 Epigenetic changes could also play a role in the disease pathogenesis. 6 For example, transcription-intermediary factor-1␥ gene (TIF1␥), whose disruption in myeloid cells induces an age-dependent CMML phenotype in the mouse, is down-regulated in leukemic cells of ϳ 35% of CMML patients because of the gene promoter hypermethylation. 7 The prognosis of this disease of the elderly is quite variable, with an approximately 2.5-year median survival. 3 BM and PB blast percentages have major prognostic value and distinguish CMML-1, with Ͻ 10% BM and Ͻ 5% PB blasts, from CMML-2 with Ն 10% BM and/or Ն 5% PB blasts. 1 Other well-documented prognostic factors include white blood cell (WBC) count, splenomegaly (SMG), extramedullary disease (EMD), cytopenias, and cytogenetic abnormalities. [8][9][10][11] ASXL1 and EZH2 mutations negatively affect the disease outcome, whereas the prognostic influence of TET2 mutation is more controversial. [12][13][14][15][16] The short survival of patients with poor prognostic factors is related to the limited availability of effective treatments. 3 The only The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. For personal use only. on March 24, 2019. by guest www.bloodjournal.org From potentially curative therapeutic option is allogeneic stem cell transplantation, however excluded in most patients by age and comorbidities. 17 In the only randomized trial conducted specifically in CMML, to our knowledge, hydroxyurea appeared more efficient than oral etoposide 18 but still associated with short survival; whereas in other reports, the response rate of CMML to low-dose cytarabine, 19 oral topotecan, 20 and intensive chemotherapy 21 remained low. The hypomethylating agents, 5-azacitidine (AZA) and 5-aza-2Ј-deoxycytidine (decitabine [DAC]) received Federal Drug Administration approval for treatment of myelodysplastic syndrome, including CMML, AZA being also approved in the European Union for CMML with marrow blasts Ͼ 10%. Pooled AZA and DAC published studies suggest an overall response rate of 39% to 45% and an overall survival (OS) benefit for responders. [22][23][24][25][26] However, CMML patient populations included in those series were generally heterogeneous. ...
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