Lenalidomide Monotherapy in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

Wiernik, Peter H.; Lossos, Izidore S.; Tuscano, Joseph M.; Justice, Glen; Vose, Julie M.; Cole, Craig E.; Lam, Wendy Wing Tak; McBride, Kyle; Wride, Kenton; Pietronigro, Dennis; Takeshita, Kenichi; Ervin-Haynes, Annette; Zeldis, Jerome B.; Habermann, Thomas M.

doi:10.1200/jco.2007.15.3429

Cited by 360 publications

(301 citation statements)

References 22 publications

(3 reference statements)

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“…[8][9][10][11][12] Studies in lymphoma and multiple myeloma (MM) models have demonstrated that lenalidomide exerts higher antitumor activity than thalidomide, has a unique capacity to stimulate the innate immune system, enhances the antitumor activity of rituximab, and inhibits angiogenesis. 13,14 The effects of lenalidomide appear to be related to the ability of immunomodulatory drug compounds to inhibit tumor necrosis factor-a, vascular endothelial growth factor, and nuclear factor kappa B (NF-KB) activity in tumor cells.…”

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confidence: 99%

“…17 Two phase 2 clinical trials (NHL-002 and NHL-003) were previously conducted to evaluate efficacy and safety of lenalidomide monotherapy in relapsed/refractory aggressive lymphoma (including DLBCL). 11,12 In these studies, the overall response rates (ORRs) in patients with DLBCL were 19% to 28%, including 7% to 12% complete responses (CRs)/unconfirmed complete responses. Responses were durable, with a median duration of response in these patients of 4.6 months.…”

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Higher response to lenalidomide in relapsed/refractory diffuse large B‐cell lymphoma in nongerminal center B‐cell–like than in germinal center B‐cell–like phenotype

Hernandez‐Ilizaliturri

Deeb

Zinzani

et al. 2011

Cancer

279

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BACKGROUND: There is a need to develop novel therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and to identify biomarkers predictive for therapeutic response. Lenalidomide was previously shown to induce an overall response rate (ORR) of 28% in patients with relapsed/refractory DLBCL. It is currently unknown if response rates differ between patients with different DLBCL subtypes. METHODS: The authors retrospectively evaluated clinical outcomes of patients with germinal center B-cell-like versus nongerminal center B-cell-like DLBCL treated with salvage lenalidomide at 4 academic institutions. RESULTS: Forty patients with relapsed/refractory DLBCL were included (24 men; 16 women; median age, 66 years; median of 4 prior treatments, including rituximab chemotherapy). Patients were classified as germinal center B-cell-like (n ¼ 23) or nongerminal center B-cell-like (n ¼ 17) DLBCL according to the Hans algorithm. The subgroups were similar in terms of stage, international prognostic index score, prior number of treatments, and rituximab resistance. A significant difference in clinical response to lenalidomide was observed in nongerminal center B-cell-like versus germinal center B-cell-like patients. ORR was 52.9% versus 8.7% (P ¼ .006); complete response rate was 23.5% versus 4.3%. Median progression-free survival was 6.2 versus 1.7 months (P ¼ .004), although no difference in OS was observed between nongerminal center B-cell-like and germinal center B-cell-like DLBCL patients. CONCLUSIONS: The data suggest that the 2 major subgroups of patients with DLBCL (germinal center B cell and nongerminal center B cell) have different antitumor responsiveness to lenalidomide in the relapsed/refractory setting. A large international trial (NCT01197560) has been opened to enrollment in an attempt to prospectively validate these retrospective observations. Cancer 2011;117:5058-

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confidence: 99%

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confidence: 99%

Higher response to lenalidomide in relapsed/refractory diffuse large B‐cell lymphoma in nongerminal center B‐cell–like than in germinal center B‐cell–like phenotype

Hernandez‐Ilizaliturri

Deeb

Zinzani

et al. 2011

Cancer

279

180

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“…Responses were durable, with a median response duration of 4.6 months.The treatment was usually well tolerated. Grade 3/4 toxicity was mainly hematologic (neutropenia and thrombocytopenia) and reversible after lenalidomide dose reduction [13,14]. Hernandez-Ilizaliturri et al [22] demonstrated that lenalidomide was more effective in non-GCB-like than GCB-like DLBCL in the R/R setting.…”

Section: Introductionmentioning

confidence: 99%

“…These effects can be explained by the ability to inhibit tumor necrosis factor-a, vascular endothelial growth factor, and NF-kB in cancer cells [19,20]. Two phase 2 trials, NHL-002 and NHL-003 [13,21], reported an overall response rate (ORR) of approximately 28%, with complete response (CR) of 7%-12%, after lenalidomide monotherapy in R/R DLBCL. Responses were durable, with a median response duration of 4.6 months.The treatment was usually well tolerated.…”

Section: Introductionmentioning

confidence: 99%

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Lenalidomide in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Is It a Valid Treatment Option?

et al. 2016

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Background. Despite the advent of new treatment strategies, many patients with diffuse large B-cell lymphoma (DLBCL) relapse or die of the disease. Prospective clinical trials have demonstrated that lenalidomide is an effective and safe treatment option, especially for non-germinal center B-cell (non-GCB) DLBCL. However, routine clinical data are lacking, which is why we provide the results of the so-far largest relapsed/refractory (R/R) DLBCL real-life analysis. Methods. We retrospectively assessed 123 R/R DLBCL patients who received either 15 or 25 mg/day of lenalidomide from January 2006 to January 2015. Results. During a median follow-up period of 4.5 years, complete remission was achieved in 32% and a partial remission in 33% non-GCB patients compared with 0% and 3% in the

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Lymphoma and Targeted Therapies

Smith

Vose

2015

Targeted Therapy in Translational Cancer Research

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Lenalidomide Monotherapy in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

Abstract: Oral lenalidomide monotherapy is active in relapsed or refractory aggressive NHL, with manageable side effects.

Cited by 360 publications

References 22 publications

Higher response to lenalidomide in relapsed/refractory diffuse large B‐cell lymphoma in nongerminal center B‐cell–like than in germinal center B‐cell–like phenotype

Higher response to lenalidomide in relapsed/refractory diffuse large B‐cell lymphoma in nongerminal center B‐cell–like than in germinal center B‐cell–like phenotype

Lenalidomide in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Is It a Valid Treatment Option?

Lymphoma and Targeted Therapies

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