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Efficacy of salvage therapy in the treatment of Helicobacter pylori-positive gastric low-grade mucosa-associated lymphoid tissue lymphoma
abstracts
Travel / Accommodation / Expenses: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Y. Dan: Full / Part-time employment: Shanghai Henlius Biotech,Inc. Y. Hong: Shareholder / Stockholder / Stock options, Full / Part-time employment: Shanghai Henlius Biotech, Inc. J. Guo: Full / Part-time employment: Shanghai Henlius Biotech, Inc. S. Zhao: Advisory / Consultancy: Certara Strategic Consulting China. X. Zeng: Research grant / Funding (institution): Peking Union Medical College Hospital. P. Hu: Research grant / Funding (institution): Peking Union Medical College Hospital. W. Jiang: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: I am an employee of Shanghai Henlius Biotech, Inc. S. Liu: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Shanghai Henlius Biotech,Inc. X. Zhang: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Shanghai Henlius Biotech,Inc. A. Luk: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Shanghai Henlius Biotech,Inc. K. Chai: Full / Part-time employment: Shanghai Henlius Biotech,Inc. E. Liu: Leadership role, Full / Part-time employment: I am an employee of Shanghai Henlius Biotech,Inc.
1081P
Efficacy of salvage therapy in the treatment of Helicobacter pyloripositive gastric low-grade mucosa-associated lymphoid tissue lymphoma
S-N. Lim1, S. Ko1, B.S. Sohn2 Internal Medicine/Hemato-Oncology, Inje University Haeundae Paik Hospital, Busan, Republic of Korea, 2Internal Medicine/Hemato-Oncology, Inje University Sanggye Paik Hospital, Seoul, Republic of Korea
1
Background: Helicobacter pylori (H.pylori) infection has a critical role in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and its eradication can lead to tumor regression. However, in patients who do not achieve a lymphoma regression or relapse following antibiotic therapy, outcome of the patients are scarce. We evaluated the long-term outcome of the patients who received salvage therapy with relapsed or refractory gastric MALT lymphoma. Methods: Between June 2000 and June 2017, a total of 29 H.pylori-positive gastric MALT lymphoma patients who received frontline H.pylori eradication were included in this study. H.pylori-positive status was defined by positive results for the biopsy urease test and histology. They had all been diagnosed by endoscopy and had a complete staging including CT-scan. Patients received standard triple therapy for eradication of H.pylori and after treatment were sequentially followed-up with endoscopies performed to evaluate the response. Tumors that had resolved to complete remission (CR) score of GELA histologic grading system were considered treatment-responsive. Results: During the follow-up periods 16 patients were refractory, nine had probable minimal residual disease and four relapsed after the first-line antibiotics. Of these 29 patients, transformation into high-grade B-cell lymphoma did not occur. Among the non-responder and relapsed patients, three patients were subjected to a watch and wait, while 26 patients underwent second-line treatment including radiotherapy (n ¼ 20), chemotherapy (n ¼ 5), chemotherapy plus sequential radiotherapy (n ¼ 1). Of the 20 patients treated with radiotherapy, the median dose to stomach was 3060 cGy (range, 1620-5000 cGy). After radiotherapy a CR was achieved in 20 patients (100%). Among six patients who received chemotherapy, a CR was achieved in five patients and no change was in one. That patient was achieved CR after radiotherapy. Probabilities of freedom from treatment failure and overall survival after 10 years were 100% and 83%.
v440 | Haematological Malignancies
Conclusions: Outcome of patients with first-line H.pylori eradication failure followed by delayed chemotherapy and/or radiotherapy on indication was excellent. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1082P
Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing
S.J. Huh Hemato-Oncology, Dong-A University Medical Center, Busan, Republic of Korea Background: Extranodal marginal zone lymphoma is a type of low-grade B-cell lymphoma and may be classified as mucosal-associated lymphoid tissue (MALT) lymphoma. MALT lymphoma is most common in stomach in Korea. The etiologic factors are inflammation caused by chronic infection, autoimmune disease and genetic variation. Identifying various somatic mutations is an essential process in precision medicine, where high throughput sequencing is used to accurately detect genetic changes. Nucleotide sequencing techniques are basically based on the Sanger method, but recently second generation or next generation sequencing (NGS) that can sequence millions or billions of DNA strands simultaneously in parallel unlike the sanger sequencing is rapidly spreading. Methods: One gastric MALT lymphoma and four small intestine MLAT lymphomas were selected and studied using tissue samples embedded in their paraffin. DNA was extracted from tissue samples and quality control was performed. NGS was performed using HemaSCANTM, a custom panel for 426 genes including essential genes for blood cancer. Results: The results of NGS revealed the following genomic variants; single nucleotide variations (SNVs), insertions and deletions (InDels) and copy number variations (CNVs). And these genomic variants are reported as annotated, known, and novel variants. Of the annotated variant, ERBB2 gene amplification was confirmed in one patient. Of the known and novel variants, SNV of SETBP6, RUNX1 and KEAP1 gene, InDel of MKI67 gene, CNV of ZNF703 and NOTCH1 gene were confirmed in two or more patients. And InDel with frameshift in BCL10, DDX3X, FOXO3 and MUC2 genes was identified in one patient. Conclusions: Since there are few NGS studies on MALT lymphoma, the various mutations identified in this study cannot be said to be “inactionable”. More studies are needed to determine the association of various genetic mutations with the development of MALT lymphoma. Editorial acknowledgement: Seok Jae Huh1, Sung Yong Oh1, Suee Lee1, Ji Hyun Lee1, Sung Hyun Kim1, Min Kyung Park2, and Hyo-Jin Kim1 1Department of Internal Medicine, Dong-A University Hospital, Busan, Republic of Korea, 2Department of Pathology, Dong-A University College of Medicine, Busan, Republic of Korea. Legal entity responsible for the study: The author. Funding: Has not received any funding. Disclosure: The author has declared no conflicts of interest.
1083P
Clinical features, treatment and outcomes of colon and rectum mucosa-associated lymphoid tissue (MALT) lymphoma: Literature reviews published in English between 1993 and 2017
J.Y. Kim Department of Colorectal Surgery, Hallym University College of Medicine, Hwasung, CA, Republic of Korea Background: Colorectal mucosa associated lymphoid tissue (MALT) lymphoma (CML) is rare and comprises only 2.5% of the MALT lymphomas. Its etiology and treatment are not well established. The aim of this systematic literature review is trying to characterize CML and analyzing treatment failure cases treated with various therapeutic strategies. Methods: We reviewed cases reports on colorectal lymphoma from 1993 to 2017. A PubMed search of the English medical literature was conducted using the search words "colon," "rectum," and "Maltoma" or “MALT lymphoma” as filters. Through the review, 65 case reports were found, of which 15 case reports were excluded, due to literature written in languages other than English, poorly documented cases and combined colonic disease such as adenocarcinoma or inflammatory bowel disease. After all, 67 patients reported in 50 studies were included from PubMed search. And we added 6 patients treated for CML in our multicenter institutes. Risk factor analysis was done for treatment failure, defined as remission failure and recurrence. Results: Of 73 patients diagnosed as CML, tumors were located in rectum in 54 patients (74.0%), 10 patients (13.6%) in right colon, 3 patients (4.1%) in the transverse colon and 6 patients (8.2%) in the sigmoid colon. The patients were achieved complete response (CR) with surgery (18/19cases), local resection (18/19 cases), chemotherapy (12/13 cases), radiation therapy (4/5cases), or antibiotics therapy including Helicobacter pylori (H. pylori) eradication (12/15 cases) in the first-line treatment.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz251.016/5577898 by guest on 26 October 2019
using Bayesian bootstrap and visual predictive check (VPC). A total of 1000 simulations were tested using the observed covariates. The final model was validated using PK samples of HLX01 and CN-RTX from a randomised, double-blind phase 3 registrational study (NCT02787239) in 110 patients with CD20þ DLBCL. Results: A two-compartment model with first-order elimination provided the best model fit. The estimated clearance (CL), central volume (Vc), peripheral compartment volume (Vp) and clearance of distribution from the central to the peripheral compartment (Q) were 27.32%, 16.56%, 21.61%, and 40.79%, respectively. The correlation between CL and Vc was 0.02239. The PopPK model of HLX01 and EU-RTX using RA patients adequately predicts the central tendency and variability of the HLX01 and CN-RTX in patients with DLBCL. Conclusions: This PopPK model derived from RA patients can predict HLX01 and CN-RTX in patients DLBCL. HLX01 and EU-/CN-RTX had similar PK parameters and influential PK covariates. These results provided further evidence for PK similarity between HLX01 and RTXs in patients with RA or DLBCL. Clinical trial identification: Two trials were listed in this abstract: 1. A Randomised, Double-blind, Phase 1/2 Study to Evaluate the PK, PD, Safety, and Efficacy Between HLX01 and Rituximab in Patients With Moderate to Severe Rheumatoid Arthritis and Inadequate Response to Treatment With DMARDs ClinicalTrials.gov Identifier: NCT03355872 2. Clinical Phase 3 Study to Compare the Efficacy and Safety of Rituximab Biosimilar HLX01 and Rituximab in Combination With CHOP, in Previously Untreated Subjects With CD20þ DLBCL ClinicalTrials.gov Identifier: NCT02787239. Legal entity responsible for the study: Shanghai Henlius Biotech, Inc. Funding: Shanghai Henlius Biotech,Inc. Disclosure:Y. Shi: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution),
Annals of Oncology
Travel / Accommodation / Expenses: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Y. Dan: Full / Part-time employment: Shanghai Henlius Biotech,Inc. Y. Hong: Shareholder / Stockholder / Stock options, Full / Part-time employment: Shanghai Henlius Biotech, Inc. J. Guo: Full / Part-time employment: Shanghai Henlius Biotech, Inc. S. Zhao: Advisory / Consultancy: Certara Strategic Consulting China. X. Zeng: Research grant / Funding (institution): Peking Union Medical College Hospital. P. Hu: Research grant / Funding (institution): Peking Union Medical College Hospital. W. Jiang: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: I am an employee of Shanghai Henlius Biotech, Inc. S. Liu: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Shanghai Henlius Biotech,Inc. X. Zhang: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Shanghai Henlius Biotech,Inc. A. Luk: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Shanghai Henlius Biotech,Inc. K. Chai: Full / Part-time employment: Shanghai Henlius Biotech,Inc. E. Liu: Leadership role, Full / Part-time employment: I am an employee of Shanghai Henlius Biotech,Inc.
1081P
Efficacy of salvage therapy in the treatment of Helicobacter pyloripositive gastric low-grade mucosa-associated lymphoid tissue lymphoma
S-N. Lim1, S. Ko1, B.S. Sohn2 Internal Medicine/Hemato-Oncology, Inje University Haeundae Paik Hospital, Busan, Republic of Korea, 2Internal Medicine/Hemato-Oncology, Inje University Sanggye Paik Hospital, Seoul, Republic of Korea
1
Background: Helicobacter pylori (H.pylori) infection has a critical role in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and its eradication can lead to tumor regression. However, in patients who do not achieve a lymphoma regression or relapse following antibiotic therapy, outcome of the patients are scarce. We evaluated the long-term outcome of the patients who received salvage therapy with relapsed or refractory gastric MALT lymphoma. Methods: Between June 2000 and June 2017, a total of 29 H.pylori-positive gastric MALT lymphoma patients who received frontline H.pylori eradication were included in this study. H.pylori-positive status was defined by positive results for the biopsy urease test and histology. They had all been diagnosed by endoscopy and had a complete staging including CT-scan. Patients received standard triple therapy for eradication of H.pylori and after treatment were sequentially followed-up with endoscopies performed to evaluate the response. Tumors that had resolved to complete remission (CR) score of GELA histologic grading system were considered treatment-responsive. Results: During the follow-up periods 16 patients were refractory, nine had probable minimal residual disease and four relapsed after the first-line antibiotics. Of these 29 patients, transformation into high-grade B-cell lymphoma did not occur. Among the non-responder and relapsed patients, three patients were subjected to a watch and wait, while 26 patients underwent second-line treatment including radiotherapy (n ¼ 20), chemotherapy (n ¼ 5), chemotherapy plus sequential radiotherapy (n ¼ 1). Of the 20 patients treated with radiotherapy, the median dose to stomach was 3060 cGy (range, 1620-5000 cGy). After radiotherapy a CR was achieved in 20 patients (100%). Among six patients who received chemotherapy, a CR was achieved in five patients and no change was in one. That patient was achieved CR after radiotherapy. Probabilities of freedom from treatment failure and overall survival after 10 years were 100% and 83%.
v440 | Haematological Malignancies
Conclusions: Outcome of patients with first-line H.pylori eradication failure followed by delayed chemotherapy and/or radiotherapy on indication was excellent. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1082P
Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing
S.J. Huh Hemato-Oncology, Dong-A University Medical Center, Busan, Republic of Korea Background: Extranodal marginal zone lymphoma is a type of low-grade B-cell lymphoma and may be classified as mucosal-associated lymphoid tissue (MALT) lymphoma. MALT lymphoma is most common in stomach in Korea. The etiologic factors are inflammation caused by chronic infection, autoimmune disease and genetic variation. Identifying various somatic mutations is an essential process in precision medicine, where high throughput sequencing is used to accurately detect genetic changes. Nucleotide sequencing techniques are basically based on the Sanger method, but recently second generation or next generation sequencing (NGS) that can sequence millions or billions of DNA strands simultaneously in parallel unlike the sanger sequencing is rapidly spreading. Methods: One gastric MALT lymphoma and four small intestine MLAT lymphomas were selected and studied using tissue samples embedded in their paraffin. DNA was extracted from tissue samples and quality control was performed. NGS was performed using HemaSCANTM, a custom panel for 426 genes including essential genes for blood cancer. Results: The results of NGS revealed the following genomic variants; single nucleotide variations (SNVs), insertions and deletions (InDels) and copy number variations (CNVs). And these genomic variants are reported as annotated, known, and novel variants. Of the annotated variant, ERBB2 gene amplification was confirmed in one patient. Of the known and novel variants, SNV of SETBP6, RUNX1 and KEAP1 gene, InDel of MKI67 gene, CNV of ZNF703 and NOTCH1 gene were confirmed in two or more patients. And InDel with frameshift in BCL10, DDX3X, FOXO3 and MUC2 genes was identified in one patient. Conclusions: Since there are few NGS studies on MALT lymphoma, the various mutations identified in this study cannot be said to be “inactionable”. More studies are needed to determine the association of various genetic mutations with the development of MALT lymphoma. Editorial acknowledgement: Seok Jae Huh1, Sung Yong Oh1, Suee Lee1, Ji Hyun Lee1, Sung Hyun Kim1, Min Kyung Park2, and Hyo-Jin Kim1 1Department of Internal Medicine, Dong-A University Hospital, Busan, Republic of Korea, 2Department of Pathology, Dong-A University College of Medicine, Busan, Republic of Korea. Legal entity responsible for the study: The author. Funding: Has not received any funding. Disclosure: The author has declared no conflicts of interest.
1083P
Clinical features, treatment and outcomes of colon and rectum mucosa-associated lymphoid tissue (MALT) lymphoma: Literature reviews published in English between 1993 and 2017
J.Y. Kim Department of Colorectal Surgery, Hallym University College of Medicine, Hwasung, CA, Republic of Korea Background: Colorectal mucosa associated lymphoid tissue (MALT) lymphoma (CML) is rare and comprises only 2.5% of the MALT lymphomas. Its etiology and treatment are not well established. The aim of this systematic literature review is trying to characterize CML and analyzing treatment failure cases treated with various therapeutic strategies. Methods: We reviewed cases reports on colorectal lymphoma from 1993 to 2017. A PubMed search of the English medical literature was conducted using the search words "colon," "rectum," and "Maltoma" or “MALT lymphoma” as filters. Through the review, 65 case reports were found, of which 15 case reports were excluded, due to literature written in languages other than English, poorly documented cases and combined colonic disease such as adenocarcinoma or inflammatory bowel disease. After all, 67 patients reported in 50 studies were included from PubMed search. And we added 6 patients treated for CML in our multicenter institutes. Risk factor analysis was done for treatment failure, defined as remission failure and recurrence. Results: Of 73 patients diagnosed as CML, tumors were located in rectum in 54 patients (74.0%), 10 patients (13.6%) in right colon, 3 patients (4.1%) in the transverse colon and 6 patients (8.2%) in the sigmoid colon. The patients were achieved complete response (CR) with surgery (18/19cases), local resection (18/19 cases), chemotherapy (12/13 cases), radiation therapy (4/5cases), or antibiotics therapy including Helicobacter pylori (H. pylori) eradication (12/15 cases) in the first-line treatment.
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz251.016/5577898 by guest on 26 October 2019
using Bayesian bootstrap and visual predictive check (VPC). A total of 1000 simulations were tested using the observed covariates. The final model was validated using PK samples of HLX01 and CN-RTX from a randomised, double-blind phase 3 registrational study (NCT02787239) in 110 patients with CD20þ DLBCL. Results: A two-compartment model with first-order elimination provided the best model fit. The estimated clearance (CL), central volume (Vc), peripheral compartment volume (Vp) and clearance of distribution from the central to the peripheral compartment (Q) were 27.32%, 16.56%, 21.61%, and 40.79%, respectively. The correlation between CL and Vc was 0.02239. The PopPK model of HLX01 and EU-RTX using RA patients adequately predicts the central tendency and variability of the HLX01 and CN-RTX in patients with DLBCL. Conclusions: This PopPK model derived from RA patients can predict HLX01 and CN-RTX in patients DLBCL. HLX01 and EU-/CN-RTX had similar PK parameters and influential PK covariates. These results provided further evidence for PK similarity between HLX01 and RTXs in patients with RA or DLBCL. Clinical trial identification: Two trials were listed in this abstract: 1. A Randomised, Double-blind, Phase 1/2 Study to Evaluate the PK, PD, Safety, and Efficacy Between HLX01 and Rituximab in Patients With Moderate to Severe Rheumatoid Arthritis and Inadequate Response to Treatment With DMARDs ClinicalTrials.gov Identifier: NCT03355872 2. Clinical Phase 3 Study to Compare the Efficacy and Safety of Rituximab Biosimilar HLX01 and Rituximab in Combination With CHOP, in Previously Untreated Subjects With CD20þ DLBCL ClinicalTrials.gov Identifier: NCT02787239. Legal entity responsible for the study: Shanghai Henlius Biotech, Inc. Funding: Shanghai Henlius Biotech,Inc. Disclosure:Y. Shi: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution),
Annals of Oncology