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Ki-67 in non-Hodgkin's lymphoma: NCI experience
abstracts
Annals of Oncology 1071PD
Treatment outcome for Helicobacter pylori-negative gastric mucosaassociated 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
1072PD
Mutational profiling through exome sequencing along with MYD88 L265P analysis could facilitate the diagnosis of vitreoretinal lymphoma
H. Lee1, B. Kim2, S-T. Lee2, J.R. Choi2 Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea, 2Department of Laboratory Medicine, Yonsei University College of Medicine Severance Hospital, Seoul, Republic of Korea
1
Background: Vitreoretinal lymphoma (VRL), previously known as intraocular lymphoma, is a rare form of malignancy. Although the disease is highly aggressive with elevated mortality rate, there are no standard of differential diagnosis from posterior uveitis when the amount of vitreous is so limited. MYD88 L265P mutation is reported to be identified in the vitreous of approximately 70% of patients with VRL. In view of the need of establishing new procedures to support the diagnosis of VRL, we explored the exome of lymphoma cells and the prevalence of MYD88 L265P mutation in Korean VRL patients. Methods: We performed the exome sequencing of vitreous of 8 patients with matched germline blood or buccal swab samples. The patients suspicious of VRL and underwent standard vitrectomy between July 2016 and September 2018 were enrolled. Sequencing data were analyzed and compared with those of CNS lymphoma. We established realtime PCR system for MYD88 L265P mutations. Vitreous of eight patients and an additional patient were subjected to the test. Results: Approximately 400 somatic mutations were identified for each patient through whole exome sequencing. Most frequetly mutated gene was MYD88. Previously reported frequently mutated genes such as PIM1 and CD79B were found to be mutated. Mutational profile of VRL showed similarity to that of PCNSL or DLBCL. Most VRL showed complex karyotype. The detection limit of MYD88 L265P real-time PCR was approximately 2%, and 5 out of 9 patients had MYD88 L265P mutation. Conclusions: MYD88 L265P real-time PCR could be a good diagnostic tool for the patients with VRL harboring MYD88 L265P mutation. We concluded that exome or gene panel testing of VRL and confirmation of the presence of a number of somatic mutation and mutation profile may facilitate the diagnosis of VRL in a subset of patients. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Volume 30 | Supplement 5 | October 2019
Prognostic value of microRNA-21/ Ki-67 in non-Hodgkin’s lymphoma: NCI experience
M. Rahouma1, R.A. Rashed2, H.A. Asker2, L.R. Abdel-Azim2, E. Naguib3, H. Khaled4 Surgical Oncology, National Cancer Institute-Cairo University, Cairo, Egypt, 2Clinical Pathology, National Cancer Institute-Cairo University, Cairo, Egypt, 3Pathology, National Cancer Institute-Cairo University, Cairo, Egypt, 4Medical Oncology, National Cancer Institute-Cairo University, Cairo, Egypt
1
Background: MicroRNA-21 (miR-21) is a small non-coding RNA that inhibits target genes expression thus affects tumorigenesis. Ki-67 is a nucleolar protein antigen in proliferating cells.Ki-67 expression is highly correlated with the proliferation rate. Immunohistochemical assay (IHC) of Ki67 antigen in paraffin section (Ki67 proliferative index) represents the active growth fraction of the tumor. We aim to evaluate the diagnostic and prognostic value of miR-21 and ki-67 as a potential biomarker of nonHodgkins lymphoma (NHL). Methods: We prospectively enrolled NHL patients (2017-2018). Serum MiR-21 and tissue Ki-67 were assessed with RT- PCR and IHC of lymph node biopsy respectively. The primary outcomes were to identify overall survival (OS), and progression free survival (PFS), while the secondary outcomes were to identify the associations between different variables and miR-21 and Ki-67. Spearman’s correlation was used and expressed as correlation coefficient (r). Kaplan-Meier survival curves were used and compared using Log-rank. Cox regression was used to identify the independent predictors of survival. Results: 80 patients were recruited with median age of 56.5 years (Inter-quartile range: 47- 64.8), 50% were males. DLBCL represented 80%. 53/73 known responses (72.6%) were responders (partial or complete response). Higher miR-21 was noticed among patients with B symptoms (r ¼ 0.304, P ¼ 0.006), higher extra-nodal number (r ¼ 0.341, P ¼ 0.002), stage IV (r ¼ 0.221, P ¼ 0.048), LDH (r ¼ 0.287, P ¼ 0.010), BMB infiltration (r ¼ 0.230, P ¼ 0.040), international prognostic index (IPI) (r ¼ 0.511, P < 0.001). Lower miR-21 was noticed among females (r¼ -0.258, P ¼ 0.021). Higher Ki-67 was noticed among old age (r ¼ 0.330, P ¼ 0.005), diffuse large B cell lymphoma (DLBCL) vs other diagnoses (r ¼ 0.315, P ¼ 0.008). On multivariable analyses, Ki-67 was associated with worse OS (HR 1.033 (95%CI 1.002-1.066), P ¼ 0.038) and PFS (HR 1.032 (95%CI 1.010-1.054), P ¼ 0.004). Conclusions: Plasma miRNA-21 may be employed as valuable non-invasive diagnostic marker in NHL. High miR-21 was noticed among high LDH, advanced stages and high IPI patients. Ki-67 is a significant predictors of overall survival, and progression free survival in NHL. Higher Ki-67 was noticed among elderly and DLBCL. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1073P
Prognostic factors influencing outcome after therapy with brentuximab vedotin in patients with relapsed or refractory Hodgkin’s lymphoma
V.S. Goranova-Marinova1, K. Ignatova2, P. Ganeva2, E. Spasov1, G. Arnaudov2, I. Micheva3, L. Gercheva3, A. Radinov4, R. Petrova4, G. Tzvetkova5, E. Hadzhiev5, L. Bogdanov6, N. Tzvetkov6, B. Spasov2, Z. Grudeva-Popova1, D. Tumbeva7 1 Clinical Hematology, Medical University Plovdiv, Plovdiv, Bulgaria, 2Hematology, SBALHZ, Sofia, Bulgaria, 3Hematology, Medical University Varna, Varna, Bulgaria, 4 Hematology, University Hospital "Sv.Ivan Rilski, Sofia, Bulgaria, 5Hematology, UMBAL "Alexandrovska", Sofia, Bulgaria, 6Hematology, Medical University Pleven, Pleven, Bulgaria, 7Clinical Hematology, UMBAL "Sv.Georgi", Plovdiv, Bulgaria Background: Brentuximab Vedotin (BV) treatment has improved the prognosis and survival of patients with Hodgkin’s lymphoma, relapsed after stem cell transplantation or having refractory disease. Aim: To analyze the prognostic factors, influencing the outcome after therapy with BV in relapsed or refractory patients with Hodgkin’s lymphoma. Methods: We studied sixty-four (64) Hodgkin’s lymphoma patients treated with BV in six Hematology clinics in Bulgaria. The male / female ratio was 1 / 1, the mean age at the time of BV therapy was 40.66þ/-13.1 years. The most common histological variant was nodular sclerosis 46 (71.9%). In the II clinical stage there were 26 patients (40.6%), in IIIrd - 17 (26.6%), in IVth - 21 (32.8%). All patients before treatment with BV received median of 4 (2-12) treatment lines, 30 ( 46.9%) received ¼/>3 lines. Autologous stem cell transplantation (autoSCT) was performed in 45 (70.3%) patients, two of which were second autologous SCTs, and in one auto/ allo SCT. Results: ORR was 60.9% (N ¼ 39). Complete response was achieved in 39.1% (25) and partial response in 21.9% (14) patients. Stable disease was registered in 10.9% (7) and progression in 28.1% (18). PFS for the entire group was 14 months. The median survival (MS) was not reached by the end of the analysis. At least partial therapeutic response was significantly higher in patients with chemosensitive disease before autoSCT ( P ¼ 0.006, R ¼ þ0.340), these who have undergone autoSCT ( P ¼ 0.021, R¼ -0.335) and when BV was started as consolidation therapy by month 3 after autoSCT ( P ¼ 0.02, R ¼ þ0.287). The only significant prognostic factor that determines a remarkably longer EFS is the type of therapeutic response itself: in the CR þ PR
doi:10.1093/annonc/mdz251 | v437
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz251.009/5577837 by guest on 26 October 2019
Background: Unlike that for Helicobacter pylori (H.pylori)-positive gastric mucosaassociated lymphoid tissue (MALT) lymphoma, the management strategy for H.pylorinegative MALT lymphoma remains controversial. Therefore, the aim of the present study was to examine the success of each treatment option for H.pylori-negative gastric MALT lymphomas. Methods: Between June 2000 and June 2017, a total of 89 H.pylori-negative gastric MALT lymphoma patients were enrolled retrospectively. 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. Tumors that had resolved to complete remission score of the GELA histologic grading system were considered treatment responsive. Results: Sixty-two patients (69.7%) underwent H.pylori eradication therapy. After H.pylori eradication, complete hematologic resonse (ChR) was achieved in 15 patients (24.2%) and pathological minimum residual disease (pMRD) in 13 (21.0%). The median time from H.pylori eradication to ChR or pMRD was 84 days. Fifteen patients received radiotherapy and all of them achieved ChR. Six patients chose combination chemotherapy with or without rituximab as follows, RCVP in 3, CVP in 1, and CHOP in 2. Two patients took subtotal gastrectomy followed by adjuvant CHOP treatment. All of them achieved ChR after chemotherapy. The clinical course after second-line treatment applied to 33 non-responders and six responders with relapse and the second-line treatments resulted in ChR in 30 patients, pMRD in one, and rRD in two patients. The rate of the ChR induction by each treatment was 100% by radiotherapy, 50% by chemotherapy. Median follow-up period was 45.4 months, lymphoma relapse was observed in nine patients (10.1%). Six patients were treated by either chemotherapy (n ¼ 2) or radiotherapy (n ¼ 3). Disease progression was observed in 3 of 33 nonresponders. Only one patient showed transformation into diffuse large B-cell lymphoma. Probabilities of overall survival and event-free survival at 10 years were 98.5%, and 61.4%, respectively. Conclusions: A substantial proportion of patients with H.pylori-negative gastric MALT lymphoma remain antibiotic-responsive and can be cured using radiotherapy and chemotherapy. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1074PD
Annals of Oncology 1071PD
Treatment outcome for Helicobacter pylori-negative gastric mucosaassociated 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
1072PD
Mutational profiling through exome sequencing along with MYD88 L265P analysis could facilitate the diagnosis of vitreoretinal lymphoma
H. Lee1, B. Kim2, S-T. Lee2, J.R. Choi2 Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea, 2Department of Laboratory Medicine, Yonsei University College of Medicine Severance Hospital, Seoul, Republic of Korea
1
Background: Vitreoretinal lymphoma (VRL), previously known as intraocular lymphoma, is a rare form of malignancy. Although the disease is highly aggressive with elevated mortality rate, there are no standard of differential diagnosis from posterior uveitis when the amount of vitreous is so limited. MYD88 L265P mutation is reported to be identified in the vitreous of approximately 70% of patients with VRL. In view of the need of establishing new procedures to support the diagnosis of VRL, we explored the exome of lymphoma cells and the prevalence of MYD88 L265P mutation in Korean VRL patients. Methods: We performed the exome sequencing of vitreous of 8 patients with matched germline blood or buccal swab samples. The patients suspicious of VRL and underwent standard vitrectomy between July 2016 and September 2018 were enrolled. Sequencing data were analyzed and compared with those of CNS lymphoma. We established realtime PCR system for MYD88 L265P mutations. Vitreous of eight patients and an additional patient were subjected to the test. Results: Approximately 400 somatic mutations were identified for each patient through whole exome sequencing. Most frequetly mutated gene was MYD88. Previously reported frequently mutated genes such as PIM1 and CD79B were found to be mutated. Mutational profile of VRL showed similarity to that of PCNSL or DLBCL. Most VRL showed complex karyotype. The detection limit of MYD88 L265P real-time PCR was approximately 2%, and 5 out of 9 patients had MYD88 L265P mutation. Conclusions: MYD88 L265P real-time PCR could be a good diagnostic tool for the patients with VRL harboring MYD88 L265P mutation. We concluded that exome or gene panel testing of VRL and confirmation of the presence of a number of somatic mutation and mutation profile may facilitate the diagnosis of VRL in a subset of patients. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Volume 30 | Supplement 5 | October 2019
Prognostic value of microRNA-21/ Ki-67 in non-Hodgkin’s lymphoma: NCI experience
M. Rahouma1, R.A. Rashed2, H.A. Asker2, L.R. Abdel-Azim2, E. Naguib3, H. Khaled4 Surgical Oncology, National Cancer Institute-Cairo University, Cairo, Egypt, 2Clinical Pathology, National Cancer Institute-Cairo University, Cairo, Egypt, 3Pathology, National Cancer Institute-Cairo University, Cairo, Egypt, 4Medical Oncology, National Cancer Institute-Cairo University, Cairo, Egypt
1
Background: MicroRNA-21 (miR-21) is a small non-coding RNA that inhibits target genes expression thus affects tumorigenesis. Ki-67 is a nucleolar protein antigen in proliferating cells.Ki-67 expression is highly correlated with the proliferation rate. Immunohistochemical assay (IHC) of Ki67 antigen in paraffin section (Ki67 proliferative index) represents the active growth fraction of the tumor. We aim to evaluate the diagnostic and prognostic value of miR-21 and ki-67 as a potential biomarker of nonHodgkins lymphoma (NHL). Methods: We prospectively enrolled NHL patients (2017-2018). Serum MiR-21 and tissue Ki-67 were assessed with RT- PCR and IHC of lymph node biopsy respectively. The primary outcomes were to identify overall survival (OS), and progression free survival (PFS), while the secondary outcomes were to identify the associations between different variables and miR-21 and Ki-67. Spearman’s correlation was used and expressed as correlation coefficient (r). Kaplan-Meier survival curves were used and compared using Log-rank. Cox regression was used to identify the independent predictors of survival. Results: 80 patients were recruited with median age of 56.5 years (Inter-quartile range: 47- 64.8), 50% were males. DLBCL represented 80%. 53/73 known responses (72.6%) were responders (partial or complete response). Higher miR-21 was noticed among patients with B symptoms (r ¼ 0.304, P ¼ 0.006), higher extra-nodal number (r ¼ 0.341, P ¼ 0.002), stage IV (r ¼ 0.221, P ¼ 0.048), LDH (r ¼ 0.287, P ¼ 0.010), BMB infiltration (r ¼ 0.230, P ¼ 0.040), international prognostic index (IPI) (r ¼ 0.511, P < 0.001). Lower miR-21 was noticed among females (r¼ -0.258, P ¼ 0.021). Higher Ki-67 was noticed among old age (r ¼ 0.330, P ¼ 0.005), diffuse large B cell lymphoma (DLBCL) vs other diagnoses (r ¼ 0.315, P ¼ 0.008). On multivariable analyses, Ki-67 was associated with worse OS (HR 1.033 (95%CI 1.002-1.066), P ¼ 0.038) and PFS (HR 1.032 (95%CI 1.010-1.054), P ¼ 0.004). Conclusions: Plasma miRNA-21 may be employed as valuable non-invasive diagnostic marker in NHL. High miR-21 was noticed among high LDH, advanced stages and high IPI patients. Ki-67 is a significant predictors of overall survival, and progression free survival in NHL. Higher Ki-67 was noticed among elderly and DLBCL. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1073P
Prognostic factors influencing outcome after therapy with brentuximab vedotin in patients with relapsed or refractory Hodgkin’s lymphoma
V.S. Goranova-Marinova1, K. Ignatova2, P. Ganeva2, E. Spasov1, G. Arnaudov2, I. Micheva3, L. Gercheva3, A. Radinov4, R. Petrova4, G. Tzvetkova5, E. Hadzhiev5, L. Bogdanov6, N. Tzvetkov6, B. Spasov2, Z. Grudeva-Popova1, D. Tumbeva7 1 Clinical Hematology, Medical University Plovdiv, Plovdiv, Bulgaria, 2Hematology, SBALHZ, Sofia, Bulgaria, 3Hematology, Medical University Varna, Varna, Bulgaria, 4 Hematology, University Hospital "Sv.Ivan Rilski, Sofia, Bulgaria, 5Hematology, UMBAL "Alexandrovska", Sofia, Bulgaria, 6Hematology, Medical University Pleven, Pleven, Bulgaria, 7Clinical Hematology, UMBAL "Sv.Georgi", Plovdiv, Bulgaria Background: Brentuximab Vedotin (BV) treatment has improved the prognosis and survival of patients with Hodgkin’s lymphoma, relapsed after stem cell transplantation or having refractory disease. Aim: To analyze the prognostic factors, influencing the outcome after therapy with BV in relapsed or refractory patients with Hodgkin’s lymphoma. Methods: We studied sixty-four (64) Hodgkin’s lymphoma patients treated with BV in six Hematology clinics in Bulgaria. The male / female ratio was 1 / 1, the mean age at the time of BV therapy was 40.66þ/-13.1 years. The most common histological variant was nodular sclerosis 46 (71.9%). In the II clinical stage there were 26 patients (40.6%), in IIIrd - 17 (26.6%), in IVth - 21 (32.8%). All patients before treatment with BV received median of 4 (2-12) treatment lines, 30 ( 46.9%) received ¼/>3 lines. Autologous stem cell transplantation (autoSCT) was performed in 45 (70.3%) patients, two of which were second autologous SCTs, and in one auto/ allo SCT. Results: ORR was 60.9% (N ¼ 39). Complete response was achieved in 39.1% (25) and partial response in 21.9% (14) patients. Stable disease was registered in 10.9% (7) and progression in 28.1% (18). PFS for the entire group was 14 months. The median survival (MS) was not reached by the end of the analysis. At least partial therapeutic response was significantly higher in patients with chemosensitive disease before autoSCT ( P ¼ 0.006, R ¼ þ0.340), these who have undergone autoSCT ( P ¼ 0.021, R¼ -0.335) and when BV was started as consolidation therapy by month 3 after autoSCT ( P ¼ 0.02, R ¼ þ0.287). The only significant prognostic factor that determines a remarkably longer EFS is the type of therapeutic response itself: in the CR þ PR
doi:10.1093/annonc/mdz251 | v437
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz251.009/5577837 by guest on 26 October 2019
Background: Unlike that for Helicobacter pylori (H.pylori)-positive gastric mucosaassociated lymphoid tissue (MALT) lymphoma, the management strategy for H.pylorinegative MALT lymphoma remains controversial. Therefore, the aim of the present study was to examine the success of each treatment option for H.pylori-negative gastric MALT lymphomas. Methods: Between June 2000 and June 2017, a total of 89 H.pylori-negative gastric MALT lymphoma patients were enrolled retrospectively. 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. Tumors that had resolved to complete remission score of the GELA histologic grading system were considered treatment responsive. Results: Sixty-two patients (69.7%) underwent H.pylori eradication therapy. After H.pylori eradication, complete hematologic resonse (ChR) was achieved in 15 patients (24.2%) and pathological minimum residual disease (pMRD) in 13 (21.0%). The median time from H.pylori eradication to ChR or pMRD was 84 days. Fifteen patients received radiotherapy and all of them achieved ChR. Six patients chose combination chemotherapy with or without rituximab as follows, RCVP in 3, CVP in 1, and CHOP in 2. Two patients took subtotal gastrectomy followed by adjuvant CHOP treatment. All of them achieved ChR after chemotherapy. The clinical course after second-line treatment applied to 33 non-responders and six responders with relapse and the second-line treatments resulted in ChR in 30 patients, pMRD in one, and rRD in two patients. The rate of the ChR induction by each treatment was 100% by radiotherapy, 50% by chemotherapy. Median follow-up period was 45.4 months, lymphoma relapse was observed in nine patients (10.1%). Six patients were treated by either chemotherapy (n ¼ 2) or radiotherapy (n ¼ 3). Disease progression was observed in 3 of 33 nonresponders. Only one patient showed transformation into diffuse large B-cell lymphoma. Probabilities of overall survival and event-free survival at 10 years were 98.5%, and 61.4%, respectively. Conclusions: A substantial proportion of patients with H.pylori-negative gastric MALT lymphoma remain antibiotic-responsive and can be cured using radiotherapy and chemotherapy. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1074PD