Lenalidomide in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Is It a Valid Treatment Option?

BACKGROUND: Despite the advent of new treatment strategies, many patients with diffuse large B-cell lymphoma (DLBCL) relapse or die of the disease. Prospective clinical trials have demonstrated that lenalidomide is an effective and safe treatment option, especially for non-germinal center B-cell (non-GCB) DLBCL. However, routine clinical data are lacking, which is why we provide the results of the so-far largest relapsed/refractory (R/R) DLBCL real-life analysis. METHODS: We retrospectively assessed 123 R/R DLBCL patients who received either 15 or 25 mg/day of lenalidomide from January 2006 to January 2015. RESULTS: During a median follow-up period of 4.5 years, complete remission was achieved in 32% and a partial remission in 33% non-GCB patients compared with 0% and 3% in the GCB group (p < .001 and .001, respectively), with median response durations of 15 and 5 months, respectively (p < .001). Lenalidomide at 25 mg was superior to 15 mg in terms of response (complete remission 21% and partial remission 23% vs. 0% and 8%; p = .007 and .05) and median response duration (10 vs. 4 months; p = .03). Toxicity was limited and reversible. Median progression-free survival differed between non-GCB and GCB patients (37 vs. 30 months; p < .001) and between the two dosages (24 vs. 34 months; p = .002). However, overall survival was similar between the subgroups (38-42 months). CONCLUSION: We provide evidence that lenalidomide is a valid treatment option for R/R DLBCL, with limited and reversible toxicity, and is more efficient in non-GCB DLBCL and at higher doses. IMPLICATIONS FOR PRACTICE: Despite the advent of new treatment strategies, many patients with diffuse large B-cell lymphoma (DLBCL) relapse or die of the disease; hence, novel therapeutic approaches are urgently needed. This study confirms that lenalidomide is a valid and well-tolerated treatment option for relapsed/refractory (R/R) DLBCL. Superior outcomes were observed in non-germinal center B-cell (GCB) DLBCL, probably because of inhibition of the nuclear factor-κB pathway. Similarly, high drug doses resulted in greater clinical benefits. Overall, lenalidomide is a suitable therapeutic option for R/R DLBCL, especially in non-GCB DLBCL, and 25 mg/day dosing should be preferred.

Bortezomib, Thalidomide and Lenalidomide: Have They Really Changed the Outcome of Multiple Myeloma?

Treatment of multiple myeloma (MM) has significantly improved, although the disease remains incurable. Prospective clinical trials evaluating the impact on outcome of new drugs such as proteasome inhibitors or immunomodulating agents are limited since they are not able to reflect the clinical routine and available retrospective data are not detailed enough to directly evaluate the value of new drugs. To address these information gaps, we performed a retrospective real-life analysis. We retrospectively assessed 949 patients treated for multiple myeloma or plasma cell leukemia at three Italian cancer centers in the years 1979-2014. Clinical features at the time of diagnosis were consistent with what was observed in clinical routine. A total of 39% of patients underwent high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). The median overall survival (OS) of the whole group was 5.4 years and ranged from 3.4 years for patients who did not receive at least one of the new drugs compared to 5.9 years in the other patients (p<0.001). The improvement in OS due to administration of new drugs was also observed among different prognostic sub-groups such as age, Durie and Salmon stage, international staging system and renal impairment. Availability of new drugs significantly improved survival of patients who underwent ASCT and also those who did not. In conclusion, we provided evidence that the advent of the new drugs drastically improved the outcome of patients with MM, also in cases with poor risk at the time of diagnosis. ASCT is still of major importance in the treatment of this disease. Nevertheless, MM remains incurable and new therapeutic approaches are warranted.

Role of blood cells dynamism on hemostatic complications in low-risk patients with essential thrombocythemia.

Patients with essential thrombocythemia (ET) aged less than 60 years, who have not suffered a previous vascular event (low-risk patients), may develop thrombotic or hemorrhagic events. So far, it has not been possible to identify useful markers capable of predicting which of these patients are more likely to develop an event and therefore who needs to be treated. In the present study, we analysed the relationship between vascular complications and longitudinal blood counts of 136 low-risk ET patients taken over a sustained period of time (blood cells dynamism). After a median follow-up of 60 months, 45 out of 136 patients (33%) suffered 40 major thrombotic and 5 severe hemorrhagic complications. A total number of 5,781 blood counts were collected longitudinally. Thrombotic and hemorrhagic events were studied together (primary endpoint) but also separately (thrombotic alone = secondary endpoint; hemorrhagic alone = tertiary endpoint). The primary endpoint showed no significant association between platelet and WBC count at diagnosis and risk of any event (platelet, p = 0.797; WBC, p = 0.178), while Hb at baseline did show an association (p = 0.024). In the dynamic analysis with Cox regression model, where the blood count values were studied by time of follow-up, we observed that the risk for Hb was 1.49 (95% CI 1.13-1.97) for every increase of 1 g/dL, and that this risk then marginally decreased during follow-up. WBC was associated with an increased risk at baseline for every increase of 1 × 10(9)/L (hazard ratio (HR) 1.07, 95% CI 1.01-1.13, p = 0.034), the risk was stable during follow-up (HR 0.95, p = 0.187 at 60 months). Also, for each increment at baseline of 100 × 10(9) platelets/L, HR was increased by 1.08 (95% CI 0.97-1.22, p = 0.159) and decreases during follow-up. In conclusion, this study is the first to evaluate in ET low-risk patients, the risk of developing a thrombotic/hemorrhagic event considering blood counts over time. Overall our study shows that the risk changes over time. For example, the risk associated with WCC is not linear as previously reported. An interesting new finding is that PLT and even Hb contribute to the risk of developing vascular events. Future treatments should take into consideration these findings and aim to control all parameters over time. We believe this early study may help develop a dynamic analysis model to predict thrombosis in the single patient. Further studies are now warranted to further validate our findings.