Long-Term Follow-Up of Elderly Patients with Acute Myeloid Leukemia Treated with Decitabine: A Real-World Study of the Apulian Hematological Network.

Decitabine, a DNA hypomethylating agent, was approved for use in adults with acute myeloid leukemia (AML) not eligible for standard chemotherapy and is now widely accepted as standard treatment. Although a number of clinical trials demonstrated its benefits in elderly AML patients, older adults and patients with frequent comorbidities are typically under-represented in such settings. Thus, the aim of the present study is to evaluate, in a real-world setting, the effectiveness and toxicity of decitabine administered as a single agent in unselected previously untreated elderly AML patients not eligible for intensive chemotherapy. In nine hematological departments of the Apulian Hematological Network (REP), we enrolled 199 patients (median age: 75.4 years; range: 61-91) with de novo (n = 94) or secondary/therapy-related (n = 105) AML treated with decitabine 20 mg/m2 for five days every 4 weeks. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using multivariate Cox regression. The average number of cycles administered per patient was 6.3 (SD: 6.0; median: 5 cycles). Complete response was achieved by 31 patients (15.6%) and partial response by 57 (28.6%), for a total of 88 responders overall (44.2%). After a median follow-up of 33.6 months, median OS was 8.7 months (95% CI: 7.4-10.3), and the 6-month, 1-year, and 3-year OS rates were 62.7%, 37.0%, and 7.1%, respectively. Mortality was increased in AML patients with ≥3 comorbidities (HR = 2.45; 95% CI: 1.18-5.08) vs. no comorbidities and in those with adverse karyotype (HR = 1.58; 95% CI: 1.05-2.38) vs. favourable or intermediate profile. Infection was the main registered adverse event (46.0%). In conclusion, this REP real-life study demonstrates, after a follow-up of almost 3 years, how decitabine administered to AML patients not suitable for intensive chemotherapy is effective and well tolerated, even in a population of truly elderly patients with frequent comorbidities.

Carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma patients: the real-life experience of Rete Ematologica Pugliese (REP).

Carfilzomib, lenalidomide, and dexamethasone (KRd) have been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial. However, its effectiveness and safety profile in real clinical practice should be further assessed. We retrospectively evaluated 130 consecutive RRMM patients treated with KRd between December 2015 and August 2018, in 9 Hematology Departments of Rete Ematologica Pugliese (REP). The overall response rate (ORR) was 79%, with 37% complete response (CR). Treatment with KRd led to an improvement in response regardless of age, refractory disease, and number and type of previous therapies. After a median follow-up of 18 months, median PFS was 24 months and 2y-PFS was 54%. PFS was longer in patients achieving a very good partial response (VGPR) with median PFS of 32.4 months. The relapses after prior autologous transplant (ASCT) positively impact median PFS. Several baseline disease characteristics, such as III ISS scoring or elevated LDH, and prior exposure to lenalidomide were found to negatively impact PFS. Primary refractory or relapsed myeloma patients have been treated with KRd as bridge to ASCT with a great benefit. Thirty-four (83%) reached at least a partial response after KRd and 21 (61%) performed ASCT. In transplanted patients, median PFS was not reached and 2y-PFS was 100%. The treatment discontinuation rate due to adverse events (AEs) was 18%, most commonly for lenalidomide (11%). Overall, in 10% of patients, a KRd dose reduction was necessary at least once (2.5% for carfilzomib and 8% for lenalidomide). The most frequent AE was neutropenia (44%) and anemia (41%). Infections occurred in 14% of patients. Cardiovascular events occurred in 11% of patients. Elderly patients have tolerated therapy very well, without additional side effects compared to younger patients, except for cardiac impairment. Our analysis confirmed that KRd is effective in RRMM patients. It is well tolerated and applicable to the majority of patients outside clinical trials. A longer PFS was shown in patients achieving VGPR, in those lenalidomide naïve and in patients relapsing after previous ASCT. Previous ASCT should not hamper the option for KRd therapy. Accordingly, KRd should be used as bridge regimen to ASCT with remarkable improvement in response and PFS rates. Further clinical studies are needed.

Azacitidine in the treatment of older patients affected by acute myeloid leukemia: A report by the Rete Ematologica Pugliese (REP).

The optimal treatment of older patients (>65 years) with acute myeloid leukemia (AML) remains challenging in daily clinical practice; a choice has to be made between intensive chemotherapy and best supportive care. To guide physicians, several prognostic factors have been identified and risk scores developed. Recently, the DNA methyltransferase inhibitor azacitidine has become available for use in MDS and AML patients with up to 30% bone marrow blasts. However, limited data are available on the outcome of older unfit AML patients, regardless of their bone marrow blast count. We retrospectively analyzed the outcome of 90 newly diagnosed older unfit AML patients in 9 Institutions from the Apulia Region (REP). Responder patients (evaluation performed after 4 cycles of treatment even in cases of primary failure) showed a better overall survival than non responders (23 vs 6 months, p<.001). ECOG PS≥2 seems to be correlated with OS in multivariate analysis, while neither primary treatment failure (documented after 2 cycles) nor bone marrow blast count were correlated with a worse overall survival either at univariate (22 vs 29 months, p=.ns; 16 vs 19 months, p=.ns) or multivariate analysis. Overall, the results of our retrospective analysis seem to confirm the efficacy of AZA treatment for this unfit AML patients setting, in terms of both CR and OS, regardless of the bone marrow blasts count, while primary treatment failure should not lead to a discontinuation of treatment.