Use of <scp>PD</scp>‐1 (<scp>PDCD</scp>1) inhibitors for the treatment of Richter syndrome: experience at a single academic centre

Rogers, Kerry A.; Huang, Ying; Dotson, Emily; Lundberg, Jordan; Andritsos, Leslie A.; Awan, Farrukh T.; Woyach, Jennifer A.; Byrd, John C.

doi:10.1111/bjh.15508

Cited by 24 publications

(13 citation statements)

References 16 publications

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Section: Biology and Features Of Dlbcl-rsmentioning

confidence: 99%

“…Recently, these results have been questioned by Rogers et al87 In case series including ten patients with RS, most of which (n=6) were treated with anti-PD-1 MoAb, pembrolizumab (n=3) and nivolumab (n=7), the median time to treatment failure and the median OS from the first dose of anti-PD-1 MoAb was 1.2 and 2 months, respectively. Importantly, all of the patients in this case series were previously exposed to ibru-tinib 87. Currently, pembrolizumab alone (NCT02576990) or in combination with ublituximab and TGR1202 (NCT02535286) or acalabrutinib (NCT02362035) or ibrutinib and idelalisib (NCT02332980) is being evaluated in RS patients in prospective studies, and the results in the context of the existing controversies described above are highly expected.…”

Section: Biology and Features Of Dlbcl-rsmentioning

confidence: 99%

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<p>Immunochemotherapy for Richter syndrome: current insights</p>

Puła

Salomon-Perzyński

Prochorec‐Sobieszek

et al. 2019

ITT

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Richter syndrome (RS) is recognized as the development of a secondary and aggressive lymphoma during the clinical course of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Most of such histological transformations are from RS to diffuse large B-cell lymphoma (DLBCL-RS, 90%) and Hodgkin’s lymphoma (HL-RS, 10%). Histopathological examination is a prerequisite for diagnosis. It is crucial to assess the relationship between the RS clone and the underlying CLL/SLL because clonally related DLBCL-RS has a poor outcome, while clonally unrelated cases have a prognosis similar to de novo DLBCL. An anti-CD20 antibody-based immunochemotherapy is hitherto the frontline treatment of choice for DLBCL-RS; nonetheless, the results are unsatisfactory. Allogeneic stem cell transplantation should be offered to younger and fit patients as a consolidative treatment; however, the majority of the patients may not be qualified for this procedure. The HL-RS transformation has better outcomes than those of DLBCL-RS and can effectively be treated by the adriamycin, bleomycin, vinblastine, and dacarbazine regimen. Although novel agents are currently being investigated for RS, immunochemotherapy nevertheless remains a standard treatment for DLBCL-RS.

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Section: Biology and Features Of Dlbcl-rsmentioning

confidence: 99%

Section: Biology and Features Of Dlbcl-rsmentioning

confidence: 99%

<p>Immunochemotherapy for Richter syndrome: current insights</p>

Puła

Salomon-Perzyński

Prochorec‐Sobieszek

et al. 2019

ITT

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“…Few panel members felt that monotherapy with PD-1 monoclonal antibodies (nivolumab or pembrolizumab) is not an effective treatment option for patients with relapsed or refractory Richter's transformation outside of a clinical trial, citing a recent report in which the use of PD-1 monoclonal antibodies for the treatment of relapsed or refractory Richter's transformation in a nontrial population (10 patients with biopsy-proven Richter's transformation to DLBCL, all of whom had received prior therapy with Bruton's tyrosine kinase inhibitors) was associated with poor efficacy and a short time to treatment failure. 39 Nivolumab and pembrolizumab with or without ibrutinib is included as an option with a category 2B recommendation for patients unable to receive chemoimmunotherapy, with del(17p) or TP53 mutation, or with chemoimmunotherapy-refractory disease (see HT-3, page 16).…”

Section: Cementioning

confidence: 99%

NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2019

Wierda¹,

Byrd²,

Abramson³

et al. 2019

J Natl Compr Canc Netw

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“…Outside clinical trial, 10 patients with active RS and without new therapeutic options were treated either by Pembrolizumab (n=3) or by Nivolumab (n=7). This “real life” experience showed a time to treatment failure of 1.2 months, with 9/10 patients relapsing ( 128 ).…”

Section: Ensuing Therapeutic Options In Rsmentioning

confidence: 96%

Microenvironment Remodeling and Subsequent Clinical Implications in Diffuse Large B-Cell Histologic Variant of Richter Syndrome

et al. 2020

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IntroductionRichter Syndrome (RS) is defined as the development of an aggressive lymphoma in the context of Chronic Lymphocytic Leukemia (CLL), with a Diffuse Large B-Cell Lymphoma (DLBCL) histology in 95% cases. RS genomic landscape shares only a few features with de novo DLBCLs and is marked by a wide spectrum of cytogenetic abnormalities. Little is known about RS microenvironment. Therapeutic options and efficacy are limited, leading to a 12 months median overall survival. The new targeted treatments usually effective in CLL fail to obtain long-term remissions in RS.MethodsWe reviewed available PubMed literature about RS genomics, PD-1/PD-L1 (Programmed Death 1/Programmed Death Ligand 1) pathway triggering and subsequent new therapeutic options.ResultsData from about 207 patients from four landmark papers were compiled to build an overview of RS genomic lesions and point mutations. A number of these abnormalities may be involved in tumor microenvironment reshaping. T lymphocyte exhaustion through PD-L1 overexpression by tumor cells and subsequent PD-1/PD-L1 pathway triggering is frequently reported in solid cancers. This immune checkpoint inhibitor is also described in B lymphoid malignancies, particularly CLL: PD-1 expression is reported in a subset of prolymphocytes from the CLL lymph node proliferation centers. However, there is only few data about PD-1/PD-L1 pathway in RS. In RS, PD-1 expression is a hallmark of recently described « Regulatory B-cells », which interact with tumor microenvironment by producing inhibiting cytokines such as TGF-β and IL-10, impairing T lymphocytes anti-tumoral function. Based upon the discovery of high PD-1 expression on tumoral B lymphocyte from RS, immune checkpoint blockade therapies such as anti-PD-1 antibodies have been tested on small RS cohorts and provided heterogeneous but encouraging results.ConclusionRS genetic landscape and immune evasion mechanisms are being progressively unraveled. New protocols using targeted treatments such as checkpoint inhibitors as single agents or in combination with immunochemotherapy are currently being evaluated.

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Use of PD‐1 (PDCD1) inhibitors for the treatment of Richter syndrome: experience at a single academic centre

Cited by 24 publications

References 16 publications

<p>Immunochemotherapy for Richter syndrome: current insights</p>

<p>Immunochemotherapy for Richter syndrome: current insights</p>

NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2019

Microenvironment Remodeling and Subsequent Clinical Implications in Diffuse Large B-Cell Histologic Variant of Richter Syndrome

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