t(11;18)(q21;q21) translocation as predictive marker for non-responsiveness to salvage thalidomide therapy in patients with marginal zone B-cell lymphoma with gastric involvement.

Abstract

PURPOSE:

Activation of TNF-α/NF-κB-related signaling pathway is crucial in sustain the growth of Helicobacter pylori-independent gastric mucosa-associated lymphoid tissue type (MALT) lymphoma. Thalidomide is an anti-angiogenic agent with anti-TNF-α and anti-NF-κB activity. This retrospective study evaluated the efficacy of thalidomide in standard therapy-failure gastric MALT lymphoma.

METHODS:

Between October 2003 and September 2007, 10 patients with antibiotics-resistant, chemotherapy-refractory gastric MALT lymphoma who received salvage thalidomide therapy at daily doses of 100-200 mg were identified from medical records and included. Status of t(11;18)(q21;q21) was determined by reverse transcriptase polymerase chain reaction for API2-MALT1 transcript, while expression of NF-κB was detected by immunohistochemistry. Tumor response was evaluated by RECIST criteria.

RESULTS:

Tumors were of stage IV in seven and IE/IIE-1 in three. The best tumor response after thalidomide was complete response in two and partial in three, with an overall response rate of 50% (95% confidence interval, 12.3-87.7%). At median follow-up of 39.3 months, the 3-year event-free and overall survival rates were 36.0% and 85.7%, respectively. API2-MALT1 transcript was detected in four (40%) tumors. Objective response rates of tumors with and without t(11;18)(q21;q21) were 0% (0/4) and 83% (5/6), respectively, P = 0.048 (Fisher's exact test). Thalidomide treatment was associated with significant down-regulation of nuclear NF-κB expression levels in residual neoplastic cells and microenvironments of responsive tumors, but not in t(11;18)(q21;q21)-positive, thalidomide-refractory tumors.

CONCLUSIONS:

Thalidomide is an effective salvage treatment for standard therapy-failure, t(11;18)(q21;q21) translocation-negative gastric MALT lymphoma and deserves further exploration.

• Authors: Sung-Hsin Kuo, Ann-Lii Cheng, Chung-Wu Lin, Chih-Hung Hsu, Ming-Shiang Wu, Kun-Huei Yeh, Yi-Shin Tzeng, Li-Tzong Chen
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 68 Issue 6 Pg. 1387-95 (Dec 2011) ISSN: 1432-0843 [Electronic] Germany
• PMID: 21465313 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• API2-MALT1 fusion protein, human
• NF-kappa B
• Oncogene Proteins, Fusion
• Thalidomide

Topics

• Aged
• Chromosomes, Human, Pair 11
• Chromosomes, Human, Pair 18
• Disease-Free Survival
• Female
• Humans
• Lymphoma, B-Cell, Marginal Zone (drug therapy, genetics, mortality, pathology)
• Male
• Middle Aged
• NF-kappa B (analysis)
• Oncogene Proteins, Fusion (genetics)
• Salvage Therapy
• Stomach Neoplasms (drug therapy, genetics, mortality, pathology)
• Thalidomide (therapeutic use)
• Translocation, Genetic