No abstract

Maintenance therapy has become a hot field in myeloma, and it may be particularly relevant in elderly patients because the major benefit results from the initial therapy. We report the results of a randomized comparison of maintenance with bortezomib plus thalidomide (VT) or prednisone (VP) in 178 elderly untreated myeloma patients who had received 6 induction cycles with bortezomib plus either melphalan and prednisone or thalidomide and prednisone. The complete response (CR) rate increased from 24% after induction up to 42%, higher for VT versus VP (46% vs 39%). Median progression-free survival (PFS) was superior for VT (39 months) compared with VP (32 months) and overall survival (OS) was also longer in VT patients compared with VP (5-year OS of 69% and 50%, respectively) but the differences did not reach statistical significance. CR achievement was associated with a significantly longer PFS (P < .001) and 5-year OS (P < .001). The incidence of G3-4 peripheral neuropathy was 9% for VT and 3% for VP. Unfortunately, this approach was not able to overcome the adverse prognosis of cytogenetic abnormalities. In summary, these maintenance regimens result in a significant increase in CR rate, remarkably long PFS, and acceptable toxicity profile. The trial is registered at www.clinicaltrials.gov as NCT00443235. (Blood. 2012;120(13): 2581-2588) IntroductionMultiple myeloma (MM) is the second most frequent hematologic malignancy and it usually affects elderly patients. Melphalan and prednisone (MP) has been the standard of care in the past for this patient population, resulting in complete response (CR) rates ranging from 2% to 5% with median overall survival (OS) from 2 to 3 years. [1][2][3] The introduction of novel agents thalidomide (Thal), bortezomib (V), and lenalidomide (R) for the treatment of elderly MM patients has significantly increased the CR rate, and this translated into prolonged time to progression (TTP), progression-free survival (PFS), and OS. Therefore, the concept of "the longer the duration of the response the longer the survival" used for most hematologic malignancies would also be applicable to MM and particularly to elderly patients because (usually) two-thirds of the survival duration in the elderly population derives from the efficacy of the first line of therapy. Accordingly, an attractive current challenge is to explore the capacity of novel agents, such as thalidomide, bortezomib, and lenalidomide to maintain the high response rate achieved upfront with these drug combinations. 4 Concerning Thal, 6 randomized trials have compared MP and Thal (MPT) with MP, 5-10 and in 3 of them Thal was also used as maintenance therapy until disease progression. 5,8,9 Maintenance induced an improvement in both overall response rate (ORR; upgrade ranging from 17% up to 30%) and PFS (prolongation ranging from 2 up to 7 months) but with only marginal benefit for OS. An Austrian trial has compared the value of Thal plus interferon maintenance versus interferon alone in elderly patients who had received inductio...

Key Points Melphalan, in combination with bortezomib, should be maintained as one of the standards of care for the treatment of elderly MM patients. Complete response and particularly flow complete response should be an important goal in the treatment of elderly myeloma patients.

Several factors hinder the identification of risk factors for central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL), including the retrospective nature of most studies, the relatively low frequency of CNS relapse in DLBCL, and the heterogeneity of CNS prophylaxis methods used in these studies. Moreover, the impact of newly developed diagnostic tools (such as multiparameter flow cytometry [FCM]) and new treatments introduced in the last decade, in particular rituximab, has still not been fully clarified.Several studies 4,5,[7][8][9][10] and a recent meta-analysis 1 have described a decrease in rates D iffuse large B-cell lymphoma patients have a 5% overall risk of central nervous system events (relapse or progression), which account for high morbidity and frequently fatal outcomes, 1 and shortened overall survival of <6 months.2 Early diagnosis of central nervous system events is critical for successful treatment and improved prognosis. Identification of patients at risk of central nervous system disease is critical to accurately identify candidates for central nervous system prophylaxis vs. therapy. [3][4][5] This report by the Spanish Lymphoma Group (GELTAMO) aims to provide useful guidelines and recommendations for the prevention, diagnosis, and treatment of central nervous system diffuse large B-cell lymphoma patients with, or at risk of, leptomeningeal and/or brain parenchyma lymphoma relapse. A panel of lymphoma experts working on behalf of GELTAMO reviewed all data published on these topics available in PubMed up to May 2016. Recommendations were classified according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach. 6 A practical algorithm based on the proposed recommendations was then developed (Figure 1 have concluded that the incidence of CNS relapse decreased after the introduction of rituximab (Table 1). The identification of risk factors has been the major goal of many studies of CNS involvement. Several large retrospective studies conducted in the pre-rituximab era [12][13][14][15] reported higher rates of CNS relapse in patients with increased serum lactate dehydrogenase (LDH) levels and/or involvement of >1 extranodal site, although these factors failed to predict CNS relapse in more than half of all cases.12 In addition to the involvement of >1 extranodal site and increased LDH, International Prognostic Index (IPI) score was also identified as an independent predictor for CNS relapse in other studies.13,16 A post-rituximab era study of 399 DLBCL patients, randomized to R-CHOP or CHOP chemotherapy, 3 identified an age-adjusted IPI (aaIPI) >1 as the only risk factor for CNS involvement, although a high aaIPI score was recorded for more than 60% of the patients. When aaIPI was excluded from the analysis, elevated LDH and a poor performance status (PS >1) were identified as independent predictive factors for CNS relapse. Similarly, in the randomized RICOVER-60 trial, 4 the combination of increased LDH levels, the involvement of >1 ex...

The presence of occult CNS involvement at diagnosis in patients with NHL at high risk of CNS disease is associated with a higher probability of CNS relapse.