Virginia Naso

Revised International Prognostic Scoring System (IPSS) Predicts Survival and Leukemic Evolution of Myelodysplastic Syndromes Significantly Better Than IPSS and WHO Prognostic Scoring System: Validation by the Gruppo Romano Mielodisplasie Italian Regional Database

PURPOSE The definition of disease-specific prognostic scores plays a fundamental role in the treatment decision-making process in myelodysplastic syndrome (MDS), a group of myeloid disorders characterized by a heterogeneous clinical behavior. PATIENTS AND METHODS We applied the recently published Revised International Prognostic Scoring System (IPSS-R) to 380 patients with MDS, registered in an Italian regional database, recruiting patients from the city of Rome (Gruppo Romano Mielodisplasie). Patients were selected based on the availability of IPSS-R prognostic factors, including complete peripheral-blood and bone marrow counts, informative cytogenetics, and follow-up data. RESULTS We validated the IPSS-R score as a significant predictor of overall survival (OS) and leukemia-free survival (LFS) in MDS (P < .001 for both). When comparing the prognostic value of the International Prognostic Scoring System (IPSS), WHO Prognostic Scoring System (WPSS), and IPSS-R, using the Cox regression model and the likelihood ratio test, a significantly higher predictive power for LFS and OS became evident for the IPSS-R, compared with the IPSS and WPSS (P < .001 for both). The multivariate analysis, including IPSS, WPSS, age, lactate dehydrogenase, ferritin concentration, Eastern Cooperative Oncology Group performance status, transfusion dependency, and type of therapy, confirmed the significant prognostic value of IPSS-R subgroups for LFS and OS. Treatment with lenalidomide and erythropoiesis-stimulating agents was shown to be an independent predictor of survival in the multivariate analysis. CONCLUSION Our data confirm that the IPSS-R is an excellent prognostic tool in MDS in the era of disease-modifying treatments. The early recognition of patients at high risk of progression to aggressive disease may optimize treatment timing in MDS.

Long-lasting remission of a relapsed large cell non-Hodgkin's lymphoma by Y90 ibritumomab tiuxetan as salvage therapy.

To the Editor: Radioimmunotherapy by Y90 ibritumomab tiuxetan, which targets the CD20 antigen, in Bcell lymphoma has clearly demonstrated efficacy and tolerability with high response rates and long durability of remission in relapsed and refractory disease1,2. Patients benefiting from this therapy include those unsuitable for myeloablative treatments and autologous stem cell transplantation3,4, as illustrated by the case observed by us and reported here. A 68-year-old woman came to our attention in January 2001 because of an enlarged left axillary lymph node. Her past medical history was unremarkable and she had no systemic symptoms. The node was removed and histological examination revealed diffuse large Bcell lymphoma (DLBCL). A comprehensive clinical and radiological workup was done. Computed tomography (CT) of the chest, abdomen and pelvis showed left axillary and subdiaphragmatic lymph nodes. A bone marrow trephine biopsy revealed no pathological findings, so the patient was considered to have clinical stage IIIA disease. According to the International Prognostic Index (IPI) score, our patient belonged to the intermediate to high risk group. She was given combination chemotherapy consisting of prednisone, doxorubicin, etoposide, cyclophosphamide, vincristine and bleomycin (P-VABEC regimen)5, by which she achieved CT-confirmed complete remission in June 2001. Six months later she presented with an enlarged node in the right axilla; surgical excision was performed and relapse of DLBCL demonstrated. Comprehensive reevaluation including whole-body CT and another trephine biopsy was done. The patient was diagnosed as having clinical stage IIIA DLBCL with the same IPI score as at Tumori, 95: 129-131, 2009

Italian real life experience with brentuximab vedotin: results of a large observational study on 40 relapsed/refractory systemic anaplastic large cell lymphoma

Between November 2012 and July 2014, in accordance with national law 648/96, brentuximab vedotin was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma outside a clinical trial context. A large Italian observational retrospective study was conducted on the use of brentuximab vedotin in everyday clinical practice to check whether clinical trial results are confirmed in a real-life context. The primary endpoint of this study was best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and safety profile. A total of 40 heavily pretreated patients were enrolled. Best response was observed after a median of four cycles in 77.5%: globally, 47.5% patients obtained a complete response, 64.2% in the elderly subset. The overall response rate was 62.5%. At the latest follow up, 15/18 patients are still in complete remission (3 with consolidation). The progression-free survival rate at 24 months was 39.1% and the disease-free survival rate at the same time was 54% (median not reached). All the long-term responders were aged <30 years at first infusion. The treatment was well tolerated even in this real-life context and no deaths were linked to drug toxicity. Brentuximab vedotin induces clinical responses quite rapidly, i.e. within the first four cycles of treatment in most responders, thus enabling timely use of transplantation. For patients ineligible for transplant or for those in whom a transplant procedure failed, brentuximab vedotin may represent a feasible effective therapeutic option in everyday clinical practice.

Aggressive lymphomas of the elderly: the DEVEC metronomic chemotherapy schedule fits the unfit

dent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. Journal of Clinical Oncology, 25, 3503–3510. Nazha, A., Narkhede, M., Radivoyevitch, T., Seastone, D.J., Patel, B.J., Gerds, A.T., Mukherjee, S., Kalaycio, M., Advani, A., Przychodzen, B., Carraway, H.E., Maciejewski, J.P. & Sekeres, M.A. (2016) Incorporation of molecular data into the Revised International Prognostic Scoring System in treated patients with myelodysplastic syndromes. Leukemia, 30, 2214–2220. Papaemmanuil, E., Gerstung, M., Malcovati, L., Tauro, S., Gundem, G., Van Loo, P., Yoon, C. J., Ellis, P., Wedge, D. C., Pellagatti, A., Shlien, A., Groves, M. J., Forbes, S. A., Raine, K., Hinton, J., Mudie, L. J., McLaren, S., Hardy, C., Latimer, C., Della Porta, M. G., O’Meara, S., Ambaglio, I., Galli, A., Butler, A. P., Walldin, G., Teague, J. W., Quek, L., Sternberg, A., Gambacorti-Passerini, C., Cross, N. C, Green, A. R., Boultwood, J., Vyas, P., Hellstrom-Lindberg, E., Bowen, D., Cazzola, M., Stratton, M. R. & Campbell, P. J.; Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium. (2013). Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood, 122, 3616– 3627.

Very long-lasting remission of refractory T-large granular lymphocytes leukemia and myeloma by lenalidomide treatment

Large granular lymphocyte leukemias (LGLLs) represent a spectrum of biologically distinct lymphoproliferative diseases originating from either mature T cells (CD3+) or natural killer (NK) cells (CD3−). Both T‐cell and NK‐cell LGL leukemia can manifest as indolent or aggressive neoplasia. These rare lymphoproliferative disorders are often associated with autoimmune diseases and impaired hematopoiesis. Symptomatic patients are treated with immunosuppressive drugs. The co‐association of T‐LGLL with clonal B‐cell disorders is reported in more than 10% of patients.

DEVEC: A PHASE II STUDY OF METRONOMIC CHEMOTHERAPY IN ELDERLY NON-FIT PATIENTS WITH AGGRESSIVE B-CELL LYMPHOMAS (PROMOTED BY FIL)

after high‐dose therapy or, in not transplant‐eligible patients (pts), after 1st‐line chemotherapy, represents an unmet clinical need. Therefore, we aimed at evaluating a salvage combination regimen (PREBEN/ PEBEN)) based on pixantrone, an aza‐anthracenadione recently approved in Europe for pts with multiply relapsed or refractory aNHL, etoposide, bendamustine and, in CD20+ tumors, rituximab. A preliminary pre‐trial experience on heavily pre‐treated pts with relapsed aNHL of B‐ or T‐cell phenotype showed good feasibility and efficacy and was previously reported. On this background, the Nordic Lymphoma Group launched an open label phase 1 (dose finding)/2 study (EudraCT no.2015‐000758‐39) testing the feasibility and efficacy of the PREBEN regimen in relapsed aNHL of B‐ or T‐cell phenotype. Here, we present the preliminary data of the first 12 enrolled pts. Methods: The trial design subdivides pts in ‘fit’ and ‘frail’ according to predefined criteria. ‘Fit’ patients enter phase 1 with a phase 2 expansion at maximum tolerated dose (MTD) level. ‘Frail’ patients enter directly phase 2 at baseline dose level. This consists of Pixantrone 50 mg/m i.v. day 1 + 8, Etoposide 100 mg i.v. day 1, Bendamustine 90 mg i.v. day 1 with or without the addition of Rituximab 375 mg/ m i.v. day 1. A maximum of 4–6 three‐weekly cycles is given. PET/ CT is performed after cycle 2 and at the end of therapy. Dose escalation is done according to a Bayesian design. Primary end‐points are MTD (phase 1) and overall response rate (ORR) (phase 2). Results: Of the 12 pts enrolled, 8 are males and 4 females. The age range is 39–80 yrs. The histological diagnosis at relapse was diffuse large B‐cell lymphoma (DLBCL) in 8 pts and peripheral T‐cell lymphoma in 4 pts. Two pts entered the phase 1 (‘fit’) trial at baseline level and 10 entered the phase 2 ‘frail’ part of the trial. All pts had IPI > 2 prior to salvage start. The mean N of previous regimens was 3 (range 1–5). Three pts had previously undergone autologous stem cell transplant. Ten pts have initiated/undergone therapy; two patients have not initiated their 1st cycle yet. Of the 10 treated pts, all had a partial (N = 6, 60%) or complete (N = 4, 40%) metabolic response (ORR 100%) after 2 cycles. One of the complete responses was seen in a previously transplanted pt with stage IV relapse including bone lesions. Response durations range between 4 and 7+ months. The treatment schedule was feasible and most patients received it on an outpatient basis. The most common grade 3–4 toxicity was of hematological type (mainly neutropenia and thrombocytopenia). At the now completed first dose level of phase 1, one MTD was recorded due to grade 4 neutropenia. Grade 3–4 infections were seen in 2 pts and were manageable. Conclusions: In this high‐risk population of relapsed aNHL, the PREBEN/PEBEN salvage schedule is feasible (outpatient regimen) and the preliminary efficacy data are promising.

Italian real-life experience with brentuximab vedotin: results of a large observational study of 40 cases of relapsed/refractory systemic anaplastic large cell lymphoma

Between November 2012 and July 2014, in accordance with national law 648/96, brentuximab vedotin was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma outside a clinical trial context. A large Italian observational retrospective study was conducted on the use of brentuximab vedotin in everyday clinical practice to check whether clinical trial results are confirmed in a real-life context. The primary endpoint of this study was best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and safety profile. A total of 40 heavily pretreated patients were enrolled. Best response was observed after a median of four cycles in 77.5%: globally, 47.5% patients obtained a complete response, 64.2% in the elderly subset. The overall response rate was 62.5%. At the latest follow up, 15/18 patients are still in complete remission (3 with consolidation). The progression-free survival rate at 24 months was 39.1% and the disease-free survival rate at the same time was 54% (median not reached). All the long-term responders were aged <30 years at first infusion. The treatment was well tolerated even in this real-life context and no deaths were linked to drug toxicity. Brentuximab vedotin induces clinical responses quite rapidly, i.e. within the first four cycles of treatment in most responders, thus enabling timely use of transplantation. For patients ineligible for transplant or for those in whom a transplant procedure failed, brentuximab vedotin may represent a feasible effective therapeutic option in everyday clinical practice.

Italian real-life experience with brentuximab vedotin

Between November 2012 and July 2014, in accordance with national law 648/96, brentuximab vedotin was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma outside a clinical trial context. A large Italian observational retrospective study was conducted on the use of brentuximab vedotin in everyday clinical practice to check whether clinical trial results are confirmed in a real-life context. The primary endpoint of this study was best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and safety profile. A total of 40 heavily pretreated patients were enrolled. Best response was observed after a median of four cycles in 77.5%: globally, 47.5% patients obtained a complete response, 64.2% in the elderly subset. The overall response rate was 62.5%. At the latest follow up, 15/18 patients are still in complete remission (3 with consolidation). The progression-free survival rate at 24 months was 39.1% and the disease-free survival rate at the same time was 54% (median not reached). All the long-term responders were aged <30 years at first infusion. The treatment was well tolerated even in this real-life context and no deaths were linked to drug toxicity. Brentuximab vedotin induces clinical responses quite rapidly, i.e. within the first four cycles of treatment in most responders, thus enabling timely use of transplantation. For patients ineligible for transplant or for those in whom a transplant procedure failed, brentuximab vedotin may represent a feasible effective therapeutic option in everyday clinical practice.

A Comparative Assessment of Quality of Life in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation Through an Outpatient and Inpatient Model

Outpatient autologous stem cell transplantation (ASCT) has proven to be feasible in terms of physical morbidity and mortality outcomes, but little data exist on the impact of this procedure on quality of life (QoL). The purpose of this prospective, observational, longitudinal cohort study was to compare the effects of inpatient (n = 76) and outpatient (n = 64) modes of care on QoL in patients with multiple myeloma who underwent ASCT. Patients were treated according to their preference for the inpatient or outpatient model. QoL was assessed using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) at baseline (7 days before ASCT; T1) and at days +7 (T2) and +30 (T3) after ASCT. Overall, inpatients achieved higher mean values at each time point (86.05 ± 15.54 at T1, 89.23 ± 19.19 at T2, and 87.96 ± 13.6 at T3) compared with outpatients (85.62 ± 14.51 at T1, 87.42 ± 23.41 at T2, and 83.98 ± 20.2 at T3), although the differences did not reach statistical significance. Inpatients showed higher mean scores than outpatients in physical well-being (7.67 ± 5.7, 15.44 ± 6.34, and 12.96 ± 6.03, respectively, versus 5.89 ± 4.33, 13.92 ± 7.05, and 8.84 ± 6.33, respectively; P < .05). Mean scores on social/family well-being were significantly higher in the outpatient group compared with the inpatient group (22.93 ± 13.29, 21.14 ± 5.31, and 21.64 ± 4.58, respectively, versus 20.59 ± 3.79, 19.52 ± 5.12, and 20.01 ± 3.97, respectively; P = .003). There were no significant between-group differences with respect to functional well-being and emotional status. Among adults at a single institution undergoing ASCT for MM, the use of outpatient care compared with standard transplantation care did not result in improved QoL during transplantation. Further research is needed for replication and to assess longer-term outcomes and implications.