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

Francisco J. Hernandez-Ilizaliturri, George Deeb, Pier L. Zinzani, Stefano A. Pileri, Farhana Malik, William R. MacOn, Andre Goy, Thomas Elmer Witzig, Myron S. Czuczman

Research output: Contribution to journalArticle

202 Citations (Scopus)

Abstract

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 = 23) or nongerminal center B-cell-like (n = 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 =.006); complete response rate was 23.5% versus 4.3%. Median progression-free survival was 6.2 versus 1.7 months (P =.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

Original languageEnglish (US)
Pages (from-to)5058-5066
Number of pages9
JournalCancer
Volume117
Issue number22
DOIs
StatePublished - Nov 15 2011

Fingerprint

Germinal Center
Lymphoma, Large B-Cell, Diffuse
B-Lymphocytes
Phenotype
lenalidomide
Therapeutics
Disease-Free Survival
Biomarkers
Drug Therapy

Keywords

  • diffuse large B-cell lymphoma
  • germinal center B-cell-like lymphoma
  • Hans algorithm
  • lenalidomide
  • nongerminal center B-cell-like lymphoma
  • relapsed/refractory

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hernandez-Ilizaliturri, F. J., Deeb, G., Zinzani, P. L., Pileri, S. A., Malik, F., MacOn, W. R., ... Czuczman, M. S. (2011). 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. Cancer, 117(22), 5058-5066. https://doi.org/10.1002/cncr.26135

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, Francisco J.; Deeb, George; Zinzani, Pier L.; Pileri, Stefano A.; Malik, Farhana; MacOn, William R.; Goy, Andre; Witzig, Thomas Elmer; Czuczman, Myron S.

In: Cancer, Vol. 117, No. 22, 15.11.2011, p. 5058-5066.

Research output: Contribution to journalArticle

Hernandez-Ilizaliturri, FJ, Deeb, G, Zinzani, PL, Pileri, SA, Malik, F, MacOn, WR, Goy, A, Witzig, TE & Czuczman, MS 2011, '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', Cancer, vol. 117, no. 22, pp. 5058-5066. https://doi.org/10.1002/cncr.26135
Hernandez-Ilizaliturri, Francisco J. ; Deeb, George ; Zinzani, Pier L. ; Pileri, Stefano A. ; Malik, Farhana ; MacOn, William R. ; Goy, Andre ; Witzig, Thomas Elmer ; Czuczman, Myron S. / 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. In: Cancer. 2011 ; Vol. 117, No. 22. pp. 5058-5066.
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abstract = "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 = 23) or nongerminal center B-cell-like (n = 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 =.006); complete response rate was 23.5{\%} versus 4.3{\%}. Median progression-free survival was 6.2 versus 1.7 months (P =.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",
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AU - Hernandez-Ilizaliturri, Francisco J.

AU - Deeb, George

AU - Zinzani, Pier L.

AU - Pileri, Stefano A.

AU - Malik, Farhana

AU - MacOn, William R.

AU - Goy, Andre

AU - Witzig, Thomas Elmer

AU - Czuczman, Myron S.

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N2 - 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 = 23) or nongerminal center B-cell-like (n = 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 =.006); complete response rate was 23.5% versus 4.3%. Median progression-free survival was 6.2 versus 1.7 months (P =.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

AB - 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 = 23) or nongerminal center B-cell-like (n = 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 =.006); complete response rate was 23.5% versus 4.3%. Median progression-free survival was 6.2 versus 1.7 months (P =.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

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