Correction to: Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Dreyling, Martin; Ghielmini, Michele; Rule, S.; Salles, Gilles; Vitolo, Umberto; Ladetto, Marco

doi:10.1093/annonc/mdx020

Cited by 34 publications

(35 citation statements)

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“…Even more promising outcomes, yet no sustainable cures, have been achieved in the treatment of indolent lymphomas (e.g. FL & MZL) employing immunochemotherapy [ 16 ]. The cumulative incidence of concurrent histological transformation in patients with indolent B-cell neoplasia have been incompletely evaluated.…”

Section: Discussionmentioning

confidence: 99%

Indolent lymphoma with composite histology and simultaneous transformation at initial diagnosis exhibit clinical features similar to de novo diffuse large B-cell lymphoma

et al. 2018

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While various studies characterized clinical and prognostic properties of de novo diffuse large B-Cell lymphoma (DLBCL) and transformed indolent lymphomas, the clinicopathological features of indolent lymphoma and simultaneous secondary transformation upon initial diagnosis (ssDLBCL) are insufficiently established.Between 2010 and 2017, 247 consecutive patients admitted to our institution and treated for DLBCL were investigated for composite histology of ssDLBCL-type. Upon systematical histopathological evaluation composite histology was identified in 22/247 cases (8.9%).The predominant histology of the underlying indolent lymphoma was follicular lymphoma of variable grading (I-IIIA; 81.8%) whereas marginal zone lymphoma represented a minor sub group (18.2%). Clinicopathological investigation revealed a high degree of concordance between ssDLBCL and de novo DLBCL upon initial diagnosis and clinical courses were shown to be strikingly similar. The predominant fraction of ssDLBCL were germinal center derived lymphomas (GCB-type) with a trend towards a superior outcome compared with non-GCB-type ssDLBCL. Additionally, we demonstrate a significant adverse prognostic impact of an underlying indolent lymphoma component other than follicular-type lymphoma (e.g. marginal zone lymphoma). Moreover, the frequency of double-hit (DHL) or double-expressor lymphomas (DEL) appears to be low.Our findings provide substantial insight into the behavior of ssDLBCL, highlight the ramifications of the concurrent high-grade fraction within indolent lymphomas and underline therapeutic efficacy of R-CHOP type immunochemotherapy in the majority of ssDLBCL patients.

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Section: Discussionmentioning

confidence: 99%

Indolent lymphoma with composite histology and simultaneous transformation at initial diagnosis exhibit clinical features similar to de novo diffuse large B-cell lymphoma

et al. 2018

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“…The recent European guidelines affirm that MRD has really got a predictive and prognostic significance, but that it is not still suitable for driving treatment of FL patients (Dreyling et al, 2017). …”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, MRD is still not a decisional tool in the routine clinical practice: indeed, the ESMO guidelines recently edited, even if clearly recognizing the prognostic role of the MRD, state that the MRD “still cannot lead the therapeutic strategy” (Dreyling et al, 2017). …”

Section: Introductionmentioning

confidence: 99%

The Combination of Rituximab and Bendamustine as First-Line Treatment Is Highly Effective in the Eradicating Minimal Residual Disease in Follicular Lymphoma: An Italian Retrospective Study

et al. 2017

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R-Bendamustine is an effective treatment for follicular lymphoma (FL). Previous large trials demonstrated the prognostic role of the molecular minimal residual disease (MRD) during the most frequently adopted chemotherapeutic regimens, but there are not yet conclusive data about the effect of combination of rituximab (R) and bendamustine in terms of MRD clearance. Thus, the aim of this retrospective study was to assess if and in what extent the combination of rituximab and bendamustine would exert a significant reduction of the molecular disease in 48 previously untreated FL patients. The molecular marker at baseline was found in the 62.5% of cases; no significant differences were observed between patients with or without the molecular marker in respect of the main clinical features. Moreover, the quantization of the baseline molecular tumor burden showed a great variability: the median value was 1.4 × 10−2 copies, ranging from 3 × 10−5 to 4 × 104. The initial molecular tumor burden did not correlate with clinical features and did not impact on the subsequent quality of response. After treatment, 93% of cases became MRD-negative; the median reduction of the BCL2/JH load was 4 logs. The 2-years PFS was 85%; it was significantly longer for patients in complete than for those in partial response (91 vs. 57%; p = 0.002), and for cases with lower FLIPI-2 score (88 vs. 60%; p = 0.004). On the contrary, PFS did not differ between patients with or without the molecular marker at baseline; a molecular tumor burden 15 times higher was observed in the relapsed subgroup in comparison to the relapse-free one, but this difference did not change the PFS length. The 2-years OS was 93.6%; the only variable that significantly impacted on it was the FLIPI-2 score; the presence of the molecular marker at baseline or its behavior after treatment did not impact on survival. This study, even if retrospective and conducted on a small series of patients, would represent a proof of concept that R-bendamustine is able to so efficaciously eradicate MRD that it could be able to by-pass the prognostic significance of MRD already demonstrated for other chemotherapeutic regimens in FL.

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“…Clinical features like night sweats and weight loss—typically associated with more aggressive forms of lymphomas such as DLBCL—might be present but are often missing even in higher stages of the disease. The ESMO recommendations appreciate the diversity of the FL subtypes, and the therapeutic options for the individual patients should be taken into consideration when planning the appropriate therapy ( 10 ).…”

Section: Clinical Presentation and Course Of Flmentioning

confidence: 99%

Cancer Immunotherapy and the Immune Response in Follicular Lymphoma

Stenner

Renner

2018

Front. Oncol.

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Follicular lymphoma (FL) is the most frequent indolent lymphoma in the Western world and is characterized in almost all cases by the t(14;18) translocation that results in overexpression of BCL2, an anti-apoptotic protein. The entity includes a spectrum of subentities that differ from an indolent to a very aggressive growth pattern. As a consequence, treatment can include watch & wait up to intensive chemotherapy including allogeneic stem cell transplantation. The immune cell microenvironment has been recognized as a major driver of outcome of FL patients and gene expression profiling has identified a clinically relevant gene expression signature that classifies an immune response to the lymphoma cells. It is known for some time that the immune cell composition of the lymphoma microenvironment is important because high numbers of tissue-infiltrating macrophages correlate with poor outcome in patients receiving chemotherapy but not in patients receiving the combination of chemotherapy and CD20-specific monoclonal antibody rituximab. In addition, TCR signaling of tumor-infiltrating lymphocytes is dysfunctional leading to an impaired capacity to form an intact immunologic synapse. Approaches restoring local T cell function, e.g., by usage of checkpoint inhibitors has demonstrated clinical activity (ORR 40%) and can achieve long-term remissions. Ongoing trials with re-programmed autologous CART cells achieve response rates in approximately 50% of FL patients with relapsed and even refractory disease. Responses lasting for more than 6 months might be durable, indicative for a successful restoration of a functional immune system. In summary, FL is a malignant disease where the control by the immune system ultimately decides about progression and transformation rate. The advent of monoclonal antibodies has changed the way we treat FL and new approaches restoring the individual immune control will hopefully improve results further.

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Correction to: Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Cited by 34 publications

References 0 publications

Indolent lymphoma with composite histology and simultaneous transformation at initial diagnosis exhibit clinical features similar to de novo diffuse large B-cell lymphoma

Indolent lymphoma with composite histology and simultaneous transformation at initial diagnosis exhibit clinical features similar to de novo diffuse large B-cell lymphoma

The Combination of Rituximab and Bendamustine as First-Line Treatment Is Highly Effective in the Eradicating Minimal Residual Disease in Follicular Lymphoma: An Italian Retrospective Study

Cancer Immunotherapy and the Immune Response in Follicular Lymphoma

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