RESUMO
In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients' triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p < 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised.
RESUMO
Salvage therapy of elderly patients with advanced, relapsed and refractory multiple myeloma (MM) is often limited by poor marrow reserve and multi-organ impairment. In particular, renal failure occurs in up to 50% of such patients, and this can potentially limit the therapeutic options. Both thalidomide and bortezomib have proven effective in these patients, with an acceptable toxicity, while, in clinical practice, lenalidomide is generally not considered a first-choice drug for MM patients with renal failure as early reports showed an increased hematological toxicity unless appropriate dose reduction is applied. Aim of this study was a retrospective evaluation of the efficacy of the combination Lenalidomide + Dexamethasone in a population of elderly MM patients treated in 5 Italian Centers. The study included 20 consecutive MM patients (9 M, 11 F, median age 76.5 years) with relapsed (N= 6) or refractory (N=13) MM and moderate to severe renal failure, defined as creatinine clearance (Cr Cl) < 50ml/min. Four patients were undergoing hemodyalisis at study entry. 85 % of the patients had been previously treated with bortezomib-containing regimens. Lenalidomide dose was adjusted according to renal function and patients clinical conditions Median treatment duration was 16 months (1-22), therapy was interrupted after 1 21-day cycle in 2 patients. Grade III-IV neutropenia was observed in 7 patients (35%); grade III-IV non hematological toxicity was recorded in 3 cases (28%). A > partial response was observed in 8 patients (40%), 1 of whom obtained a VGPR; 4 additional patients achieved a minor response. Median response duration was 16 months (range 2-19+ months). A complete and partial renal response was obtained in 4 and 3 patients, respectively, all of them were responsive to Lenalidomide-dexamethasone According to our data, LEN+DEX has shown efficacy and acceptable toxicity in this population of elderly patients with advanced MM and renal failure.
RESUMO
Diagnosis and monitoring of multiple myeloma (MM) and related conditions are usually carried out by means of serum and urine protein electrophoresis and immunofixation. In the early 2000s, an assay aimed at evaluating serum free light chains (sFLCs) was made available and subsequently tested in different plasma cell disorders. Several reports have demonstrated the usefulness of the assay for the diagnosis and monitoring of oligosecretory MM, nonsecretory MM, Bence Jones MM, and amyloid light-chain amyloidosis. Furthermore, a prognostic role for an abnormal sFLC κ/λ ratio has been observed in the case of monoclonal gammopathy of unknown significance, smoldering MM, solitary plasmacytomas, and in newly diagnosed symptomatic MM secreting intact monoclonal immunoglobulins. In conclusion, according to present data, the sFLC assay can be considered reliable for the diagnosis, monitoring, and prognosis of different plasma cell disorders, and recently studies have been carried out to test a possible role of an sFLC evaluation in other B-cell lymphoproliferative malignancies.
RESUMO
The role of high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) in the treatment armamentarium of aggressive B- and T-cell non-Hodgkin lymphoma (NHL) is still a matter of debate. In the pre-Rituximab era, the PARMA study demonstrated the superiority of HDT/ASCT over conventional salvage chemotherapy in chemosensitive, relapsed patients. Subsequently, HDT/ASCT has become a standard approach for relapsed NHL. With the advent of Rituximab in the landscape of NHL, transplantation as part of first-line therapy has been challenged. However, no benefit in terms of disease-free or overall survival of HDT/ASCT over standard therapy was shown when Rituximab was added to both arms. Moreover, the superiority of HDT/ASCT over conventional salvage therapy in patients relapsing from first-line therapy including Rituximab was not confirmed. From these disappointing results, novel strategies, which can enhance the anti-lymphoma effect, at the same time reducing toxicity have been developed, with the aim of improving the outcome of HDT/ASCT in aggressive NHL. In T-cell lymphoma, few publications demonstrated that consolidation of complete remission with HDT/ASCT is safe and feasible. However, up to one-third of patients may never receive transplant, mostly due to progressive disease, and relapse still remains a major concern even after transplant.