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In this randomized phase 2 study (GEM-KyCyDex), the combination of weekly carfilzomib 70 mg/m2, cyclophosphamide and dexamethasone was compared to carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines (PLs). 197 patients were included and randomized 1:1 to receive KCd (97 patients) or Kd (100 patients) in 28-day cycles until progressive disease or unacceptable toxicity occurred. Patient median age was 70 years, and the median number of PLs was 1 (1-3). More than 90% of patients had previously been exposed to proteasome inhibitors, ≈70% to immunomodulators, and ≈50% were refractory to their last line (mainly lenalidomide) in both groups. After a median follow-up of 37 months, median progression-free survival (PFS) was 19.1 and 16.6 months in KCd and Kd, respectively (P=0.577). Of note, in the post hoc analysis of the lenalidomiderefractory population, the addition of cyclophosphamide to Kd resulted in a significant benefit in terms of PFS: 18.4 vs. 11.3 months (Hazard ratio 1.7 [1.1-2.7]; P=0.043). The overall response rate and the percentage of patients who achieved complete response was around 70% and 20% in both groups. The addition of cyclophosphamide to Kd did not result in any safety signal, except for severe infections (7% vs. 2%). In conclusion, the combination of cyclophosphamide with Kd 70 mg/m2 weekly does not improve outcomes as compared with Kd alone in RRMM after 1-3 PLs, but a significant benefit in PFS was observed with the triplet in the lenalidomide-refractory population. The administration of weekly carfilzomib 70 mg/m2 was safe and convenient, and, overall, the toxicity was manageable in both arms.

Resumen Fundamento y objetivo El curso clinico de los pacientes con leucemia linfatica cronica de celulas B (LLCB) es extremadamente heterogeneo y no hay indices pronosticos (IP) que permitan clasificar bien a estos pacientes. En este estudio se han analizado 2 nuevos IP propuestos por el MDACC (MD Anderson Cancer Center) y por el grupo GIMEMA (Gruppo Italiano Malattie Ematologiche Maligne dell′ Adulto). Pacientes y metodo Se ha realizado un estudio de seguimiento de una cohorte de pacientes diagnosticados de LLCB (265 casos) en el area sanitaria de Gijon durante 10 anos (de 1997 a 2007), y de la supervivencia de los pacientes segun los sistemas de estadificacion clasica (Rai y Binet) y los nuevos IP. Resultados Las tasas bruta y ajustada fueron de 8,99 y de 3,47 cada 100.000 habitantes por ano, respectivamente. El indice GIMEMA no fue util para predecir la supervivencia global. La distribucion segun el IP MDACC fue la siguiente: el 31,4% de bajo riesgo, el 62% de riesgo intermedio y el 6,6% de alto riesgo. La probabilidad de supervivencia a los 5 y 10 anos fue del 87 y el 73% para el bajo riesgo, del 75 y el 49% para el riesgo intermedio, y del 29 y el 16% para el de alto riesgo. Conclusiones Las tasas de incidencia de LLCB son superiores a las descritas hasta ahora, posiblemente debido a una mejor recogida de datos y a un diagnostico mas precoz. En este estudio se demuestra por primera vez en una poblacion no seleccionada de pacientes que el IP MDCAA predice mejor la supervivencia que los sistemas de estadificacion clasica. Dada su simplicidad, este modelo pronostico puede ser muy util para el manejo de los pacientes en la practica clinica.

The introduction of novel antimyeloma therapies, including thalidomide, lenalidomide, and bortezomib, has expanded treatment options for patients with this disease. These compounds have altered the natural history of multiple myeloma, resulting in substantial improvements in patient outcomes. However, like with any other drug, their use is associated with a specific toxicity profile. The major adverse events (AEs) associated with lenalidomide include: hematological toxicities (myelosuppression), mainly neutropenia, venous thromboembolism, gastrointestinal disturbance, skin toxicity, atrial fibrillation, asthenia, and decreased peripheral blood stem cell yield during stem cell collection when lenalidomide is used after a long period of time. These AEs are predictable, consistent, and manageable with patient monitoring, supportive care, and dose adjustment. In this article, using three clinical cases as examples, we discuss the diagnoses and management of the most frequent AEs associated with lenalidomide treatment in patients with multiple myeloma.

The introduction of new agents in the treatment of multiple myeloma, such as thalidomide, bortezomib, or lenalidomide, has represented an important step forward in the management of this disease, with improvement in both treatment response and patient survival. On the other hand, when new drugs are used it is very important to know their associated toxicity, since adequate management of the adverse effects can help to avoid unnecessary treatment interruptions — thereby undoubtedly contributing to improvement in the efficacy of therapy. The present study reviews the main hematological and nonhematological adverse effects potentially associated with the use of lenalidomide in its most common combinations used for the treatment of multiple myeloma, and the recommendations for dealing with such effects.

The clinical course of B-chronic lymphocytic leukemia (B-CLL) patients is highly heterogeneous and the prognosis of these patients is difficult to predict. In this study, we analysed two new prognostic indexes proposed by the MDACC and GIMEMA group in a random population of B-CCL patients.A follow up study of a cohort of patients was carried out. 265 B-CLL patients diagnosed in the Area Sanitaria de Gijón during 10 years (1997-2007) were analysed in this study. The overall survival of the patients was analysed by the Rai and Binet staging systems and the prognostic indexes proposed by the MDACC and GIMEMA group.The crude rate was 8.99 per 100.000 populations for year and the adjusted-age rate was 3.47 per 100.000 populations for year. The distribution of patients based on the MDACC index was: 31.4% had low risk, 62% had intermediate risk and 6.6% had high risk. The percentage of 5- and 10-years survival probabilities were 87% and 73% for low risk, 75% and 49% for intermediate risk and 29% and 16% of high risk. The GIMEMA index was unable to predict the overall survival in our patients.The rates of B-CLL are higher in our population than previously described, which is probably caused by an earlier diagnosis. Our results indicate that the MDACC prognostic index predicted the overall survival and the prognosis of a random population of patients better than the classical staging systems. The simplicity and utility of this prognostic index may help clinicians in clinical decision and therapeutical management.