- Email: [email protected]
refractory classical Hodgkin lymphoma
abstracts 60P LC
Immune checkpoint inhibitors in treatment in patients with relapsed/refractory HIV-related lymphomas
Background: Immune check point inhibitors (ICIs) is a new option for salvage therapy in relapsed/refractory (r/r) Hodgkin lymphoma (HL) and non-Hodgkin lymphoma. Patients with HIV-related lymphoma may benefit not only anticancer activity of ICIs, but also from its potential anti-HIV effect [1]. The publications on ICIs in HIV-related lymphomas is limited by a few case reports [2,3]. Methods: Nine patients with r/r HIV-related lymphoma were treated with nivolumab (nivo) between 2017-2019. Median follow-up time was 397 days [45-889]. The end points were response to therapy, immune-related adverse effects (IRAE) and overall survival (OS) at 12 months. LYRIC criteria for assessing FDG-PET/CT were applied. Results: The main characteristics of study population and outcomes are presented on picture 1. Median number of prior lines of therapy was 3 (range, 2-4). Four patients received low dose of nivo as monotherapy [NCT03343665] with median N of courses 12 [7-12], 5 patients in combi with bendamustine and gemcitabine [NCT03259529] with median N of courses 4 [3-11]. The median of CD4þ was 382 c/mcl (range, 45560). The only one patient didn’t receive cART due acute renal failure who died early from undetermined cause. Overall response rate (ORR) was 89% with the median time 104 days [73-517]; complete remission (CR) was 67% with the median time 107 days [75-265]. IRAE was not registered. OS at 12 months was 88,9%. Conclusion: Overall response rate to nivo in patients with HIV-related lymphomas was 89%, one-year OS – 88,9%. Immune-related adverse effects were not registered. Preliminary data provide that nivo seems to be an effective and safety treatment option for r/r HIV-related lymphoma. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
61P
Immunotherapy in patients with relapsed/refractory HIV-related lymphomas
M. Popova1, Y. Rogacheva2, I. Tsygankov1, K. Lepik1, Y. Zalyalov1, L. Stelmakh1, I. Moiseev1, S. Bondarenko1, N. Mikhaylova1, V. Baykov3, B. Afanasyev1 1 Hematology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 2Hematology, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation, 3Pathology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation Background: Immune checkpoint inhibitors (ICIs) are a new option for salvage therapy in relapsed/refractory (r/r) Hodgkin lymphoma (HL) and non-Hodgkin lymphoma. Patients with HIV-related lymphoma may benefit not only from the anticancer
activity of ICIs, but also from its potential anti-HIV effect. The publications on ICIs in HIV-related lymphomas is limited by a few case reports. Methods: Nine patients with r/r HIV-related lymphoma were treated with nivolumab (nivo) between 2017-2019. Median follow-up time was 397 days [45-889]. The end points were response to therapy, immune-related adverse effects (IRAE) and overall survival (OS) at 12 months. LYRIC criteria for assessing FDG-PET/CT were applied. Results: The main characteristics of the study population and outcomes are presented in the table. Median number of prior lines of therapy was 3 (range, 2-4). Four patients received low dose of nivo as monotherapy [NCT03343665] with median of 12 courses 12 (7-12), 5 patients in combination with bendamustine and gemcitabine [NCT03259529] with median of 4 courses 4 (3-11). The median of CD4þ was 382 c/ mcl (range, 45-560). The only one patient who did not receive cART due to acute renal failure died early from undetermined cause. Overall response rate (ORR) was 89% with the median time 104 days (73-517); complete remission (CR) was 67% with the median time 107 days (75-265). IRAE were not registered. OS at 12 months was 88.9%. Conclusion: Overall response rate to nivo in patients with HIV-related lymphomas was 89%, one-year OS – 88.9%. Immune-related adverse effects were not registered. Preliminary data suggest that nivo seems to be an effective and safety treatment option for r/r HIV-related lymphoma. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
62P
Safety and efficacy of allogeneic stem cell transplantation after nivolumab therapy for patients with relapsed/refractory classical Hodgkin lymphoma
A. Beynarovich1, K. Lepik2, N. Mikhailova3, E. Kondakova2, Y. Zalyalov2, I. Moiseev2, B. Afanasyev2 1 Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation, 2Hematology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 3Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Scientific Research Institute of Pediatric Oncology, Hematology and Transplantology, St. Petersburg, Russian Federation Background: The programmed-death 1 (PD-1) blockade with nivolumab has demonstrated high efficiency in patients with relapsed and refractory Hodgkin lymphoma (rrHL) with an acceptable toxicity profile. However, most patients treated with immune checkpoint inhibitors (CPIs) will eventually progress on these therapies. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) is a potentially curative option for patients with rrHL. There are concerns that CPIs before allo- HSCT may increase the incidence of graft-versus-host disease, immune-related adverse events, and nonrelapse mortality (NRM). At present, there is no consensus regarding the optimal transplant strategy for patients previously treated with immune checkpoint blockade. The aim of this study was to evaluate outcomes in patients with rrHL who received CPIs as a bridge to allo-HSCT. Methods: We evaluated the results of allo-HSCT in 20 patients who had been transplanted after prior PD-1 blockade between 2017 and 2019 . All patients received reduced-intensity conditioning regimen and post-transplant cyclophosphamide (PTCy)-based GvHD prophylaxis. The best response to PD-1 therapy was a complete
Table: 61P
xi22 | Clinical Practice
Volume 30 | Supplement 11 | December 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_11/mdz449.016/5675220 by University of New England user on 10 February 2020
M. Popova1, Y. Rogacheva2, I. Tsygankov1, K. Lepik1, L. Stelmah3, I. Moiseev1, S. Bondarenko1, N. Mikhaylova3, V. Baykov4, B. Afanasyev1 1 Hematology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, Saint Petersburg, Russian Federation, 2Hematology, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russian Federation, 3Oncology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, Saint Petersburg, Russian Federation, 4 Pathology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, Saint Petersburg, Russian Federation
Annals of Oncology
abstracts
Annals of Oncology
63P
Influence of nivolumab on epidemiology of infectious complications in patients with relapse or refractory Hodgkin’s lymphoma
Y. Rogacheva1, M. Popova2, K. Lepik2, E. Kondakova2, Y. Zalyalov2, L. Stelmah3, A. Volkova4, I. Nikolaev5, O. Goloshchapov6, I. Barhatov2, S. Bondarenko2, I. Moiseev2, V. Baykov7, N. Mikhailova2, N. Klimko8, B. Afanasyev2 1 Hematology, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation, 2Hematology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 3Oncology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 4 Pneumonology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 5Radiology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 6Reanimatology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 7Pathology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 8Mycology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation Background: The clinical development of checkpoint inhibitor-based immunotherapy has ushered in an exciting era of anticancer therapy. Despite many reports on anti PD-1 antibody therapy for the treatment of Hodgkin’s lymphoma (HL), the risk of infection among patients receiving nivolumab (nivo) is still unknown. Methods: Between 2016 and 2018, 112 patients with r/r HL were observed and treated with nivo (3 mg/kg) in CIC 725. The median number of nivo courses received was 20 (range, 1-30). 18 patients underwent allo-HSCT after therapy with nivo. The median follow-up period was 1.4 years (1 month-2.6 year). All patients had a standard antiinfective prophylaxis and treatment according to the international guidelines. Results: During salvage treatment with nivo of r/r HL 11 (10%) patients had documented infection episodes (n ¼ 16): bacterial infections – 37.5% (n ¼ 6), invasive fungal diseases (IFD) – 25% (n ¼ 4) and viral infections – 37.5% (n ¼ 6). The median time to infection episodes was 98 days (12-365) after first nivo administration. Incidence of bacterial infections in study cohort was 5.3% (n ¼ 6). Two patients developed pneumonia, others with one: sinusitis, meningitis cause by Listeria meningitis, colitis and gonitis. Incidence of viral infections was 5.3% (n ¼ 6): pneumonia associated with HHP-6 and CMV in 50% and generalized infections in 50% caused by HSV-1,2 and HHV-6. IFD were diagnosed in 3.6% patients (n ¼ 4). The main etiology agent was Aspergillus spp. in 50%. Primary chemoresistant disease before nivo therapy was the only risk factor of infection complications during treatment of r/r HL (p ¼ 0,029). Overall survival (OS) at 1 year after first nivo administration in study cohort was 96.5%. Only one death was attributed to infection; the patient died due to sepsis of unknown etiology. Conclusion: Incidence of infectious complications in r/r HL treated with nivo was 10%. Etiology of infectious complications presented by bacterial infections –37.5%, invasive fungal diseases – 25% and viral infections – 37.5%. Primary chemoresistance was a risk factor for infection complications. Wherewith infections could be managed successfully and carry favorable prognosis. 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 11 | December 2019
64P
Immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with advanced hepatocellular carcinoma: Does the sequence matter?
J. Lee1, K. Ng1, L. Wong1, A. Ang1, S.H. Tan2, D. Tai1, S.P. Choo1 Medical Oncology, National Cancer Centre Singapore, Singapore, 2Biostatistics and Epidemiology Unit, National Cancer Centre Singapore, Singapore
1
Background: Tyrosine kinase inhibitors (TKI) are the first-line systemic treatment for patients with advanced hepatocellular carcinoma (HCC), while immune checkpoint inhibitors (ICI) were approved for use in the second-line setting in 2018. Results of phase III studies evaluating the role of first-line ICI use are pending. It is unknown if the sequencing of therapy of TKI and ICI makes a difference in response rate, nor if TKIs can be safely used in the third-line setting after ICI. Methods: Of 114 patients with advanced HCC treated with an ICI at our institution between 30 Dec 2013 and 13 Jun 2018, 59 who also received a TKI were retrospectively identified. Patients were classified into three categories: Group 1, those who had received TKI before an ICI (TKI1-ICI), Group 2 included those who received an ICI followed by an TKI (ICI-TKI2), and Group 3 included those who received a TKI both before and after ICI (TKI1-ICI-TKI2). Response evaluation was done based on RECIST v1.1. Results: 28 patients received TKI1-ICI, 24 received ICI-TKI2, and 7 received TKI1-ICITKI2. Median OS was 12.1, 13.9, 31.2m in groups 1, 2 and 3 respectively (p ¼ 0.20), while PFS was 3.1, 2.1 and 3.7 m. (p ¼ 0.40) Response rate to TKI was 3.6%, 12.5% and 28.6% respectively for Group 1, 2 and 3 (p ¼ 0.10), and disease control rate was 21.4%, 25.0% and 71.4% respectively (p ¼ 0.04). 65.7% of the patients who received TKI before ICI experienced adverse events of any grade, similar to 61.3% of patients who received TKI after ICI. The rate of grade 3 or higher adverse events were also similar at 5.8% and 9.7%. There were no grade 5 adverse events. Conclusion: DCR with TKI was higher when sequenced after ICI and even higher when sequenced after both prior TKI and ICI, suggesting that there may be a role for defining the sequence or combination of TKI and ICI in patients with HCC. No new safety signals were seen with use of TKI following ICI. Legal entity responsible for the study: Sing Health CIRB. Funding: Bayer. Disclosure: J. Lee: Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy: Ipsen. D. Tai: Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Sirtex; Honoraria (self), Advisory / Consultancy: Bayer; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eisai. S.P. Choo: Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (self): Sirtex; Advisory / Consultancy: Novartis; Advisory / Consultancy: Eisai; Advisory / Consultancy: Bayer; Advisory / Consultancy: Celgene. All other authors have declared no conflicts of interest.
65P
Determination of anti-pancreatic islet cell antibodies for the prevention of type 1 diabetes mellitus as an immune-related adverse event secondary to treatment with immune checkpoint inhibitors
A. Olivares Hernandez1, R.A. Escala Cornejo2, L. Figuero Pe´rez1, M.R. Vidal Tocino1, E. Escalera Martın1, J. Claros Ampuero1, A. Amores Martin1, C.A. Rodrıguez Sanchez1, R. Gonzalez Sarmiento3, J.P. Miramontes Gonzalez4, J.J. Cruz-Hernandez1 1 Department of Medical Oncology, Salamanca University Healthcare Complex, Salamanca, Spain, 2Medical Oncology, Avila Healthcare Complex, Avila, Spain, 3Clinical Research, Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain, 4 Internal Medicine, Valladolid University Healthcare Complex, Valladolid, Spain Background: Type 1 diabetes mellitus (T1D) as an immune-mediated effect of immunotherapy-based oncology treatments is observed in 0.5-5% of the patients. Prevention of these symptoms is based on the determination of the basal sugar levels on an empty stomach after the administration of each dose of the drug. The objective of this clinical review is assessing the incorporation of anti-pancreatic islet cell antibodies in the prevention of these events. Methods: A clinical review was carried out with the published cases of T1D secondary to immunotherapy between the years 2012 and 2019 in the current medical literature. We analyzed the determination of anti-pancreatic islet cell antibodies in patients who presented diabetes as an immune-mediated effect, as well as their phenotypic characteristics, the analysis levels and the drugs that had been used.
doi:10.1093/annonc/mdz449 | xi23
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response in 9 patients, partial response in 4; 5 patients received transplant during the disease progression and 2 patients were transplanted in indetermined response. Results: At the time of analysis, median follow-up was 14 months (range, 1-26 months). The 1-year OS and EFS were 95% and 85% respectively, whereas the 1-year cumulative incidences of relapse and NRM were 10% and 5% respectively. Two patients with relapse after allo-HSCT were treated with donor lymphocyte infusion (DLI) in combination with chemotherapy. At the median follow up of 30 days all patients remain alive. 4/20 patients developed severe grade 3-4 GvHD and only 1 patient responded to steroids. The cumulative incidence of chronic GVHD (cGVHD) was 35%. Conclusion: Our study demonstrates that HSCT after PD-1 blockade is feasible and not associated with higher mortality. The rate of severe acute and chronic GvHD was relatively higher than previously reported for PTCy-based prophylaxis, but was manageable in the majority of cases. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Immune checkpoint inhibitors in treatment in patients with relapsed/refractory HIV-related lymphomas
Background: Immune check point inhibitors (ICIs) is a new option for salvage therapy in relapsed/refractory (r/r) Hodgkin lymphoma (HL) and non-Hodgkin lymphoma. Patients with HIV-related lymphoma may benefit not only anticancer activity of ICIs, but also from its potential anti-HIV effect [1]. The publications on ICIs in HIV-related lymphomas is limited by a few case reports [2,3]. Methods: Nine patients with r/r HIV-related lymphoma were treated with nivolumab (nivo) between 2017-2019. Median follow-up time was 397 days [45-889]. The end points were response to therapy, immune-related adverse effects (IRAE) and overall survival (OS) at 12 months. LYRIC criteria for assessing FDG-PET/CT were applied. Results: The main characteristics of study population and outcomes are presented on picture 1. Median number of prior lines of therapy was 3 (range, 2-4). Four patients received low dose of nivo as monotherapy [NCT03343665] with median N of courses 12 [7-12], 5 patients in combi with bendamustine and gemcitabine [NCT03259529] with median N of courses 4 [3-11]. The median of CD4þ was 382 c/mcl (range, 45560). The only one patient didn’t receive cART due acute renal failure who died early from undetermined cause. Overall response rate (ORR) was 89% with the median time 104 days [73-517]; complete remission (CR) was 67% with the median time 107 days [75-265]. IRAE was not registered. OS at 12 months was 88,9%. Conclusion: Overall response rate to nivo in patients with HIV-related lymphomas was 89%, one-year OS – 88,9%. Immune-related adverse effects were not registered. Preliminary data provide that nivo seems to be an effective and safety treatment option for r/r HIV-related lymphoma. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
61P
Immunotherapy in patients with relapsed/refractory HIV-related lymphomas
M. Popova1, Y. Rogacheva2, I. Tsygankov1, K. Lepik1, Y. Zalyalov1, L. Stelmakh1, I. Moiseev1, S. Bondarenko1, N. Mikhaylova1, V. Baykov3, B. Afanasyev1 1 Hematology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 2Hematology, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation, 3Pathology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation Background: Immune checkpoint inhibitors (ICIs) are a new option for salvage therapy in relapsed/refractory (r/r) Hodgkin lymphoma (HL) and non-Hodgkin lymphoma. Patients with HIV-related lymphoma may benefit not only from the anticancer
activity of ICIs, but also from its potential anti-HIV effect. The publications on ICIs in HIV-related lymphomas is limited by a few case reports. Methods: Nine patients with r/r HIV-related lymphoma were treated with nivolumab (nivo) between 2017-2019. Median follow-up time was 397 days [45-889]. The end points were response to therapy, immune-related adverse effects (IRAE) and overall survival (OS) at 12 months. LYRIC criteria for assessing FDG-PET/CT were applied. Results: The main characteristics of the study population and outcomes are presented in the table. Median number of prior lines of therapy was 3 (range, 2-4). Four patients received low dose of nivo as monotherapy [NCT03343665] with median of 12 courses 12 (7-12), 5 patients in combination with bendamustine and gemcitabine [NCT03259529] with median of 4 courses 4 (3-11). The median of CD4þ was 382 c/ mcl (range, 45-560). The only one patient who did not receive cART due to acute renal failure died early from undetermined cause. Overall response rate (ORR) was 89% with the median time 104 days (73-517); complete remission (CR) was 67% with the median time 107 days (75-265). IRAE were not registered. OS at 12 months was 88.9%. Conclusion: Overall response rate to nivo in patients with HIV-related lymphomas was 89%, one-year OS – 88.9%. Immune-related adverse effects were not registered. Preliminary data suggest that nivo seems to be an effective and safety treatment option for r/r HIV-related lymphoma. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
62P
Safety and efficacy of allogeneic stem cell transplantation after nivolumab therapy for patients with relapsed/refractory classical Hodgkin lymphoma
A. Beynarovich1, K. Lepik2, N. Mikhailova3, E. Kondakova2, Y. Zalyalov2, I. Moiseev2, B. Afanasyev2 1 Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation, 2Hematology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 3Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Scientific Research Institute of Pediatric Oncology, Hematology and Transplantology, St. Petersburg, Russian Federation Background: The programmed-death 1 (PD-1) blockade with nivolumab has demonstrated high efficiency in patients with relapsed and refractory Hodgkin lymphoma (rrHL) with an acceptable toxicity profile. However, most patients treated with immune checkpoint inhibitors (CPIs) will eventually progress on these therapies. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) is a potentially curative option for patients with rrHL. There are concerns that CPIs before allo- HSCT may increase the incidence of graft-versus-host disease, immune-related adverse events, and nonrelapse mortality (NRM). At present, there is no consensus regarding the optimal transplant strategy for patients previously treated with immune checkpoint blockade. The aim of this study was to evaluate outcomes in patients with rrHL who received CPIs as a bridge to allo-HSCT. Methods: We evaluated the results of allo-HSCT in 20 patients who had been transplanted after prior PD-1 blockade between 2017 and 2019 . All patients received reduced-intensity conditioning regimen and post-transplant cyclophosphamide (PTCy)-based GvHD prophylaxis. The best response to PD-1 therapy was a complete
Table: 61P
xi22 | Clinical Practice
Volume 30 | Supplement 11 | December 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_11/mdz449.016/5675220 by University of New England user on 10 February 2020
M. Popova1, Y. Rogacheva2, I. Tsygankov1, K. Lepik1, L. Stelmah3, I. Moiseev1, S. Bondarenko1, N. Mikhaylova3, V. Baykov4, B. Afanasyev1 1 Hematology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, Saint Petersburg, Russian Federation, 2Hematology, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russian Federation, 3Oncology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, Saint Petersburg, Russian Federation, 4 Pathology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, Saint Petersburg, Russian Federation
Annals of Oncology
abstracts
Annals of Oncology
63P
Influence of nivolumab on epidemiology of infectious complications in patients with relapse or refractory Hodgkin’s lymphoma
Y. Rogacheva1, M. Popova2, K. Lepik2, E. Kondakova2, Y. Zalyalov2, L. Stelmah3, A. Volkova4, I. Nikolaev5, O. Goloshchapov6, I. Barhatov2, S. Bondarenko2, I. Moiseev2, V. Baykov7, N. Mikhailova2, N. Klimko8, B. Afanasyev2 1 Hematology, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation, 2Hematology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 3Oncology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 4 Pneumonology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 5Radiology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 6Reanimatology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 7Pathology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation, 8Mycology, Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, St. Petersburg, Russian Federation Background: The clinical development of checkpoint inhibitor-based immunotherapy has ushered in an exciting era of anticancer therapy. Despite many reports on anti PD-1 antibody therapy for the treatment of Hodgkin’s lymphoma (HL), the risk of infection among patients receiving nivolumab (nivo) is still unknown. Methods: Between 2016 and 2018, 112 patients with r/r HL were observed and treated with nivo (3 mg/kg) in CIC 725. The median number of nivo courses received was 20 (range, 1-30). 18 patients underwent allo-HSCT after therapy with nivo. The median follow-up period was 1.4 years (1 month-2.6 year). All patients had a standard antiinfective prophylaxis and treatment according to the international guidelines. Results: During salvage treatment with nivo of r/r HL 11 (10%) patients had documented infection episodes (n ¼ 16): bacterial infections – 37.5% (n ¼ 6), invasive fungal diseases (IFD) – 25% (n ¼ 4) and viral infections – 37.5% (n ¼ 6). The median time to infection episodes was 98 days (12-365) after first nivo administration. Incidence of bacterial infections in study cohort was 5.3% (n ¼ 6). Two patients developed pneumonia, others with one: sinusitis, meningitis cause by Listeria meningitis, colitis and gonitis. Incidence of viral infections was 5.3% (n ¼ 6): pneumonia associated with HHP-6 and CMV in 50% and generalized infections in 50% caused by HSV-1,2 and HHV-6. IFD were diagnosed in 3.6% patients (n ¼ 4). The main etiology agent was Aspergillus spp. in 50%. Primary chemoresistant disease before nivo therapy was the only risk factor of infection complications during treatment of r/r HL (p ¼ 0,029). Overall survival (OS) at 1 year after first nivo administration in study cohort was 96.5%. Only one death was attributed to infection; the patient died due to sepsis of unknown etiology. Conclusion: Incidence of infectious complications in r/r HL treated with nivo was 10%. Etiology of infectious complications presented by bacterial infections –37.5%, invasive fungal diseases – 25% and viral infections – 37.5%. Primary chemoresistance was a risk factor for infection complications. Wherewith infections could be managed successfully and carry favorable prognosis. 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 11 | December 2019
64P
Immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with advanced hepatocellular carcinoma: Does the sequence matter?
J. Lee1, K. Ng1, L. Wong1, A. Ang1, S.H. Tan2, D. Tai1, S.P. Choo1 Medical Oncology, National Cancer Centre Singapore, Singapore, 2Biostatistics and Epidemiology Unit, National Cancer Centre Singapore, Singapore
1
Background: Tyrosine kinase inhibitors (TKI) are the first-line systemic treatment for patients with advanced hepatocellular carcinoma (HCC), while immune checkpoint inhibitors (ICI) were approved for use in the second-line setting in 2018. Results of phase III studies evaluating the role of first-line ICI use are pending. It is unknown if the sequencing of therapy of TKI and ICI makes a difference in response rate, nor if TKIs can be safely used in the third-line setting after ICI. Methods: Of 114 patients with advanced HCC treated with an ICI at our institution between 30 Dec 2013 and 13 Jun 2018, 59 who also received a TKI were retrospectively identified. Patients were classified into three categories: Group 1, those who had received TKI before an ICI (TKI1-ICI), Group 2 included those who received an ICI followed by an TKI (ICI-TKI2), and Group 3 included those who received a TKI both before and after ICI (TKI1-ICI-TKI2). Response evaluation was done based on RECIST v1.1. Results: 28 patients received TKI1-ICI, 24 received ICI-TKI2, and 7 received TKI1-ICITKI2. Median OS was 12.1, 13.9, 31.2m in groups 1, 2 and 3 respectively (p ¼ 0.20), while PFS was 3.1, 2.1 and 3.7 m. (p ¼ 0.40) Response rate to TKI was 3.6%, 12.5% and 28.6% respectively for Group 1, 2 and 3 (p ¼ 0.10), and disease control rate was 21.4%, 25.0% and 71.4% respectively (p ¼ 0.04). 65.7% of the patients who received TKI before ICI experienced adverse events of any grade, similar to 61.3% of patients who received TKI after ICI. The rate of grade 3 or higher adverse events were also similar at 5.8% and 9.7%. There were no grade 5 adverse events. Conclusion: DCR with TKI was higher when sequenced after ICI and even higher when sequenced after both prior TKI and ICI, suggesting that there may be a role for defining the sequence or combination of TKI and ICI in patients with HCC. No new safety signals were seen with use of TKI following ICI. Legal entity responsible for the study: Sing Health CIRB. Funding: Bayer. Disclosure: J. Lee: Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy: Ipsen. D. Tai: Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Sirtex; Honoraria (self), Advisory / Consultancy: Bayer; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eisai. S.P. Choo: Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (self): Sirtex; Advisory / Consultancy: Novartis; Advisory / Consultancy: Eisai; Advisory / Consultancy: Bayer; Advisory / Consultancy: Celgene. All other authors have declared no conflicts of interest.
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Determination of anti-pancreatic islet cell antibodies for the prevention of type 1 diabetes mellitus as an immune-related adverse event secondary to treatment with immune checkpoint inhibitors
A. Olivares Hernandez1, R.A. Escala Cornejo2, L. Figuero Pe´rez1, M.R. Vidal Tocino1, E. Escalera Martın1, J. Claros Ampuero1, A. Amores Martin1, C.A. Rodrıguez Sanchez1, R. Gonzalez Sarmiento3, J.P. Miramontes Gonzalez4, J.J. Cruz-Hernandez1 1 Department of Medical Oncology, Salamanca University Healthcare Complex, Salamanca, Spain, 2Medical Oncology, Avila Healthcare Complex, Avila, Spain, 3Clinical Research, Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain, 4 Internal Medicine, Valladolid University Healthcare Complex, Valladolid, Spain Background: Type 1 diabetes mellitus (T1D) as an immune-mediated effect of immunotherapy-based oncology treatments is observed in 0.5-5% of the patients. Prevention of these symptoms is based on the determination of the basal sugar levels on an empty stomach after the administration of each dose of the drug. The objective of this clinical review is assessing the incorporation of anti-pancreatic islet cell antibodies in the prevention of these events. Methods: A clinical review was carried out with the published cases of T1D secondary to immunotherapy between the years 2012 and 2019 in the current medical literature. We analyzed the determination of anti-pancreatic islet cell antibodies in patients who presented diabetes as an immune-mediated effect, as well as their phenotypic characteristics, the analysis levels and the drugs that had been used.
doi:10.1093/annonc/mdz449 | xi23
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response in 9 patients, partial response in 4; 5 patients received transplant during the disease progression and 2 patients were transplanted in indetermined response. Results: At the time of analysis, median follow-up was 14 months (range, 1-26 months). The 1-year OS and EFS were 95% and 85% respectively, whereas the 1-year cumulative incidences of relapse and NRM were 10% and 5% respectively. Two patients with relapse after allo-HSCT were treated with donor lymphocyte infusion (DLI) in combination with chemotherapy. At the median follow up of 30 days all patients remain alive. 4/20 patients developed severe grade 3-4 GvHD and only 1 patient responded to steroids. The cumulative incidence of chronic GVHD (cGVHD) was 35%. Conclusion: Our study demonstrates that HSCT after PD-1 blockade is feasible and not associated with higher mortality. The rate of severe acute and chronic GvHD was relatively higher than previously reported for PTCy-based prophylaxis, but was manageable in the majority of cases. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.