Ibrutinib Monotherapy in Relapsed or Refractory, Transformed Diffuse Large B-cell Lymphoma

Graf, Solomon A.; Cassaday, Ryan D.; Morris, Karolyn; Voutsinas, Jenna M.; Wu, Qian Vicky; Behnia, Fatemeh; Lynch, Ryan C.; Krakow, Elizabeth F.; Rasmussen, Heather E.; Chauncey, Thomas R.; Kanan, Sandra; Soma, Lorinda; Smith, Stephen D.; Gopal, Ajay K.

doi:10.1016/j.clml.2020.11.023

Cited by 5 publications

(5 citation statements)

References 30 publications

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“…In the SCHOLAR-1 study, R/R DLBCL patients treated with chemotherapy regimens showed an ORR of 26%, complete response (CR) rate of 7%, and a median OS of 6.2 months ( 17 ). Like R/R DLBCL, R/R tDLBCL also has a poor prognosis, likely due to acquired chemoresistance and host features, including immunoparesis and poor treatment tolerance ( 7 ). Currently, there are no standard treatments for R/R tDLBCL, and patients are usually treated following a similar approach as that for R/R DLBCL.…”

Section: Discussionmentioning

confidence: 99%

“…Regrettably, relapsed/refractory (R/R) transformed DLBCL (tDLBCL) is not included in most clinical trials for R/R indolent B-cell non-Hodgkin lymphoma or R/R de novo DLBCL, resulting in the lack of evidence on novel treatments. Recently, some novel agents, such as lenalidomide and ibrutinib, have demonstrated moderate efficacy in R/R tDLBCL with manageable adverse events ( 7 , 8 ), yet the efficacy of current therapies is still unsatisfactory.…”

Section: Introductionmentioning

confidence: 99%

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Sintilimab and Chidamide for Refractory Transformed Diffuse Large B Cell Lymphoma: A Case Report and A Literature Review

et al. 2021

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Patients with relapsed/refractory (R/R) transformed diffused large B cell lymphoma (tDLBCL) have a poor prognosis and a low survival rate. In addition, no standard therapy has yet been established for R/R tDLBCL. Herein we presented a single case of a patient with R/R tDLBCL who was successfully treated with sintilimab and chidamide. The patient was a 71-year-old man with pulmonary mucosa-associated lymphoid tissue lymphoma. He did not receive any treatment until tDLBCL was confirmed 2 years later. The tDLBCL was primary refractory to R2-CHOP, R2-MTX, and Gemox regimens. However, the patient achieved sustained complete remission after the combination therapy of sintilimab and chidamide. To the best of our knowledge, this is the first report of sintilimab combined with chidamide for the treatment of R/R tDLBCL, which opens up new therapeutic possibilities for this new combination therapy in future prospective clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sintilimab and Chidamide for Refractory Transformed Diffuse Large B Cell Lymphoma: A Case Report and A Literature Review

et al. 2021

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“…Based on the clinical evidence, ibrutinib has been given the United States Food and Drug Administration (FDA) approval for the treatment of multiple B cell malignances, including CLL/small lymphocytic lymphoma (SLL), MCL, marginal zone lymphoma (MZL) and Waldenstrom macroglobulinemia (WM) (Hendriks et al, 2014;Pal Singh et al, 2018;Zi et al, 2019;Bond and Maddocks, 2020;Castillo et al, 2020b;Grimont et al, 2020;Hanna et al, 2020;Noy et al, 2020;Treon et al, 2021). Furthermore, ibrutinib, as monotherapy or in combination therapies with other targeted drugs (such as anti-CD20, anti-PD-1/PD-L1 and inhibitors of Bcl-2, PI-3Kδ or proteosome), has demonstrated efficacy in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Richter's transformation (RT), multiple myeloma (MM), B cell pro-lymphocytic leukemia (B-PLL), acute lymphoblastic leukemia (ALL), lymphoproliferative disorders (LPD), and primary and secondary central nervous system lymphomas (PCNSL/SCNSL) in recent clinical trials (Hendriks et al, 2014;Pal Singh et al, 2018;Chari et al, 2020;Chen et al, 2020;Fowler et al, 2020;Oka et al, 2020;Schaffer et al, 2020;Graf et al, 2021;Hodkinson et al, 2021;Lewis et al, 2021). However, a unique set of toxicities has also been reported, even though ibrutinib is generally more tolerable than chemoimmunotherapy (CIT) regimens.…”

Section: Introductionmentioning

confidence: 99%

Multifaceted Immunomodulatory Effects of the BTK Inhibitors Ibrutinib and Acalabrutinib on Different Immune Cell Subsets – Beyond B Lymphocytes

Zhu

Gokhale

Jung

et al. 2021

Front. Cell Dev. Biol.

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The clinical success of the two BTK inhibitors, ibrutinib and acalabrutinib, represents a major breakthrough in the treatment of chronic lymphocytic leukemia (CLL) and has also revolutionized the treatment options for other B cell malignancies. Increasing evidence indicates that in addition to their direct effects on B lymphocytes, both BTK inhibitors also directly impact the homeostasis, phenotype and function of many other cell subsets of the immune system, which contribute to their high efficacy as well as adverse effects observed in CLL patients. In this review, we attempt to provide an overview on the overlapping and differential effects of ibrutinib and acalabrutinib on specific receptor signaling pathways in different immune cell subsets other than B cells, including T cells, NK cells, monocytes, macrophages, granulocytes, myeloid-derived suppressor cells, dendritic cells, osteoclasts, mast cells and platelets. The shared and distinct effects of ibrutinib versus acalabrutinib are mediated through BTK-dependent and BTK-independent mechanisms, respectively. Such immunomodulatory effects of the two drugs have fueled myriad explorations of their repurposing opportunities for the treatment of a wide variety of other human diseases involving immune dysregulation.

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“…The second paper consists of a study assessing ibrutinib monotherapy in patients with relapsed or refractory DLBCL. Of the 20 patients included, two were originally diagnosed with LPL [ 12 ]. The overall response rate was 35% with an overall survival of 22.4 months.…”

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confidence: 99%

“…The overall response rate was 35% with an overall survival of 22.4 months. Interestingly, the response was not found to depend on the original lymphoma subtype [ 12 ]. However, one patient discontinued therapy early and one patient passed away while on therapy; the specific details on the two LPL patients including the presence or absence of the MYD88 L265P mutation were not given.…”

mentioning

confidence: 99%

Ibrutinib response in cutaneous transformed lymphoplasmacytic lymphoma

Lindholm

Forsberg

Ewalt

2021

eJHaem

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Ibrutinib Monotherapy in Relapsed or Refractory, Transformed Diffuse Large B-cell Lymphoma

Cited by 5 publications

References 30 publications

Sintilimab and Chidamide for Refractory Transformed Diffuse Large B Cell Lymphoma: A Case Report and A Literature Review

Sintilimab and Chidamide for Refractory Transformed Diffuse Large B Cell Lymphoma: A Case Report and A Literature Review

Multifaceted Immunomodulatory Effects of the BTK Inhibitors Ibrutinib and Acalabrutinib on Different Immune Cell Subsets – Beyond B Lymphocytes

Ibrutinib response in cutaneous transformed lymphoplasmacytic lymphoma

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