We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41.6%, clinical benefit 60.9%. Median progression-free and median overall survival were 6 and 20 months, respectively. Overall, no differences emerged by pertuzumab pretreatment, with median progression-free and median overall survival of 4 and 17 months in pertuzumab-pretreated (p=0.13), and 6 and 22 months in pertuzumab-naïve patients (p=0.27). Patients who received second-line T-DM1 had median progression-free and median overall survival of 3 and 12 months (p=0.0001) if pertuzumab-pretreated, and 8 and 26 months if pertuzumab-naïve (p=0.06). In contrast, in third-line and beyond, median progression-free and median overall survival were 16 and 18 months in pertuzumab-pretreated (p=0.05) and 6 and 17 months in pertuzumab-naïve patients (p=0.30). In multivariate analysis, lower ECOG performance status was associated with progression-free survival benefit (p<0.0001), while overall survival was positively affected by lower ECOG PS (p<0.0001), absence of brain metastases (p 0.05), and clinical benefit (p<0.0001). Our results are comparable with those from randomized trials. Further studies are warranted to confirm and interpret our data on apparently lower T-DM1 efficacy when given as second-line treatment after pertuzumab, and on the optimal sequence order.

The prognostic value of lymphocyte doubling time (LDT), expressed in months and obtained by means of a linear regression, has been studied in 99 previously untreated chronic lymphocytic leukemia (CLL) patients. LDT is defined as the period of time needed for lymphocytes to double in number the amount found at diagnosis. When the analysis was extended to the whole population, it showed clear differences in the life expectancy of patients with LDT of less than or equal to 12 months (median survival, 36 months; relative death rate [O/E]1.57) compared with those with LDT of more than 12 months (median survival not yet reached; O/E, 0.37) (P less than 0.001). The significance of LDT remained even after adjustments were made for age, sex, lymphocyte count, anemia, and thrombocytopenia. The lack of statistical significance after adjustment for Binet's clinical stage corresponds to the fact that clinical stages are not distributed homogeneously, high LDT being more frequently associated with earlier stages and low LDT with more advanced forms of the disease (P less than 0.001). In this study LDT was a useful parameter in predicting disease progression. Patients in Stages A and B and with rapidly increasing lymphocytes counts became worse more frequently (33.3% and 29.1%, respectively, at 12 months after diagnosis) than those with a slow increase (no change in clinical stage at 12 months). It is concluded that since LDT appears to predict the progression of the disease, it is useful in the clinical management of CLL.

The reduced toxicity and the documented low rate of marginal failures make the adaptive approach a modern option for future randomized studies. The best scenario to confirm its application is probably in neoadjuvant chemoradiation trials.

Clinical and biological data were evaluated using Desu univariate analyses or Cox multivariate analyses in a series of 1,777 chronic lymphocytic leukemia (CLL) patients from an Italian Cooperative Group. In univariate analyses, age and sex of patients, presence of bone marrow (BM; greater than or equal to 50%), and peripheral blood (PB; greater than or equal to 60,000/microL) lymphocytosis, anemia (hemoglobin [Hb] less than 11 g/dL), thrombocytopenia (less than 100,000/microL), direct Coombs' test positivity, hepatomegaly, splenomegaly, and extent of lymph node involvement were shown to be of significant prognostic value. Multivariate analyses, through a stepwise procedure, showed that the most important prognostic variables are Hb, hepatomegaly, lymph node involvement, PB lymphocytosis, and age and sex of patients. Further covariates would produce an improvement having a nonsignificant P value. Based on the results of multivariate analyses, a four-step staging using the significant variables of the Cox model is proposed.

Fifty‐three patients affected with B‐cell chronic lymphocytic leukemia (CLL) younger than 50 years and observed in two hematological institutions have been retrospectively evaluated in order to verify whether this disease has different clinico‐hematological features at presentation and different prognosis as compared to older cases. In our experience young cases with B‐CLL diagnosis, confirmed by immunophenotype in 90.5% of patients, accounted for 7.1% of the whole CLL population. Sex distribution, mean peripheral lymphocyte count, platelet count, distribution among Rai's and Binet's stages, total tumor mass (TTM) score, histological pattern of bone marrow infiltration and lymphocyte doubling time (LDT) were similar to a series of 201 CLL cases older than 50 years. Only hemoglobin mean level was significantly higher in younger patients (13.1 ± 2.1 vs 12.2 ± 2.6 g/dl; p<0.01). The overall median survival was 7.1 years. Rai and Binet staging classifications and TTM score system retained their prognostic value in this CLL population. In addition, cases fulfilling criteria of “smoldering” CLL, had a very long survival (75% survival probability at 16 years). Life‐expectancy of younger patients was significantly longer than that of older ones (median survival, 7.1 versus 4.1 years; p < 0.05). However, when the background mortality due to non‐CLL related deaths (i.e., cardiovascular complications, epithelial cancers) was removed, survival advantage of young cases disappeared. In conclusion this study confirms that prognosis of young CLL patients can be easily assessed using the current well‐defined criteria. Since age is not by itself a criterion for intensifying treatment, further efforts to identify those young CLL patients who qualify for more aggressive therapy should be made.