Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi

Chiappella, Annalisa; Tucci, Alessandra; Castellino, Alessia; Pavone, Vincenzo; Baldi, Ileana; Carella, Angelo Michele; Orsucci, Lorella; Zanni, Manuela; Salvi, Flavia; Liberati, Anna Marina; Gaïdano, Gianluca; Bottelli, Chiara; Rossini, Bernardo; Perticone, Sonia; Masi, Pasqualina De; Ladetto, Marco; Ciccone, Giovannino; Palumbo, Antônio; Rossi, Giuseppe; Vitolo, Umberto

doi:10.3324/haematol.2013.085134

Cited by 54 publications

(37 citation statements)

References 41 publications

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“…Grade 4 neutropenia was reported in 31 % of the courses and no grade 4 extra-hematological toxicities and no toxic deaths were recorded. After a median follow-up of 28 months, the 2-year overall survival (OS) was 92 % and 2-year PFS was 80 %[21,22]. In line with the in vitro results, lenalidomide was more…”

supporting

confidence: 82%

“…Based on these promising results in the relapsed/refractory DLBCL setting and, since the outcome of some patients undergoing R-CHOP is not yet satisfying, trials evaluating the association of lenalidomide with standard immunochemotherapy were initiated. Firstly, the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLT) of lenalidomide plus R-CHOP in newly diagnosed DLBCL were determined in phase I trials [21][22][23]. In [14] translocation t (14;18), such as most FL [33].…”

Section: Immunomodulatory Agentsmentioning

confidence: 99%

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Changing treatment paradigms in lymphoma: new targets and new drugs

Mian

Chiappella²

2015

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The knowledge about biological mechanisms contributing to lymphomagenesis represents the basis for targeted therapies in lymphoproliferative disorders. Herein, we provide a short overview about the novel drugs targeting B-cell non-Hodgkin lymphomas, with a focus on diffuse large B-cell lymphomas. Due to the plethora of new drugs, we present some of the most important new drug developments in lymphoma treatment, namely humanized monoclonal antibodies, monoclonal antibody conjugates, immunomodulatory agents, and tyrosine kinase inhibitors. The use of these agents alone or in combination with chemotherapy showed promising results with a good safety profile in a setting of relapsed/refractory lymphomas. Since many of them demonstrated to be highly active, several clinical trials evaluating their efficacy in first-line treatment are ongoing.

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confidence: 82%

Section: Immunomodulatory Agentsmentioning

confidence: 99%

Changing treatment paradigms in lymphoma: new targets and new drugs

Mian

Chiappella²

2015

memo

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“…Such new agents are designed to target the different specific oncogenic pathways disrupted in DLBCL. 36,37 Regarding NOTCH pathway targeting, it has recently been reported that γ-secretase inhibitor PF-03084014 inhibits the constitutive NOTCH activation and induces selective apoptosis in CLL cells carrying NOTCH1 mutations. 38 In conclusion, in this study, we document that NOTCH activation pathway mutations are a molecular clue associated to approximately 25% of HCV-positive cases among DLBCL and that among HCV-positive DLBCL, the molecular deregulation of NOTCH signaling associates with the co-existence of a low-grade component in the diagnostic biopsy and poor outcome.…”

Section: Discussionmentioning

confidence: 99%

The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

et al. 2014

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“…There is evidence that both lenalidomide 79 and the inhibitor of Bruton's tyrosine kinase ibrutinib 80 are active in ABC-type DLBCL. Several groups are exploring R-CHOP in combination with lenalidomide (R 2 -CHOP) [81][82][83][84] and ibrutinib in nodal DLBCL. The data available so far suggest that these combinations are well tolerated and effective, although to the best of our knowledge, patients with PTL are not specifically being studied.…”

Section: Future Directionsmentioning

confidence: 99%

Primary testicular lymphoma

Cheah

Wirth

Seymour

2014

Blood

178

174

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Primary testicular lymphoma (PTL) is a rare, clinically aggressive form of extranodal lymphoma. The vast majority of cases are histologically diffuse large B-cell lymphoma, but rarer subtypes are clinically important and must be recognized. In this review, we discuss the incidence, clinical presentation, and prognostic factors of PTL and present a summary of the recent advances in our understanding of its pathophysiology, which may account for the characteristic clinical features. Although outcomes for patients with PTL have historically been poor, significant gains have been made with the successive addition of radiotherapy (RT), full-course anthracycline-based chemotherapy, rituximab and central nervous system–directed prophylaxis. We describe the larger retrospective series and prospective clinical trials and critically examine the role of RT. Although rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given every 21 days with intrathecal methotrexate and locoregional RT is the current international standard of care, a substantial minority of patients progress, representing an unmet medical need. Finally, we discuss new treatment approaches and recent discoveries that may translate into improved outcomes for patients with PTL.

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Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi

Cited by 54 publications

References 41 publications

Changing treatment paradigms in lymphoma: new targets and new drugs

Changing treatment paradigms in lymphoma: new targets and new drugs

The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

Primary testicular lymphoma

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