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Differences in Outcome of Patients with Syncytial Variant Hodgkin Lymphoma (HL) Compared with Typical Nodular Sclerosis HL
Abstracts noticed an increase in the use of PET-CT: 65% of patients had a PET-CT at diagnosis (p: 0.0001). 66% of patients had a PET-CT at the end of treatment by 2010. The usage of CT at diagnosis has dropped significantly from 92.9% prior to 2009 to 54.4% after 2010 (p¼0.0001). We also observed in patients with advanced HL a decrease in the usage of 8 cycles of ABVD protocol from 9.5% in 1990-1999 to 5.9% in 2000-2009 to 4.5% in 2010-2015 (p¼0.5). Conclusion: Functional imaging techniques are gaining popularity over anatomical imaging. The usage of PET-CT has emerged as a highly valuable staging and follow up method in the treatment of HL 8 years after the introduction of PET in Lebanon, it was used at first to improve the staging, then to evaluate response to treatment and recently for tailoring therapy according to response.
the salvage group. After a median follow up of 9 months, only 2 patients (22%) in the maintenance group progressed and all patients are still alive. Conversely, in the salvage group, 4 patients (67%) progressed and 1 patient developed secondary AML and died. Conclusion: BV therapy showed an efficacy only as maintenance treatment after auto-SCT but was less successful when used as post-transplant salvage in R/R HL. Four cycles of maintenance may suffice. Prospective trials with larger samples are warranted to support these findings. Table 1 Patients Characteristics Characteristics
N (%)
Age at BV initiation Median (range)
HL-160 Post Transplant Brentuximab Maintenance Appears more Effective than Post Transplant Salvage Brentuximab for Relapsed /Refractory Hodgkin Lymphoma
Male
9 (60)
Female
6 (40)
HL subtype Nodular Sclerosis Unknown Prior transplant
Amanda Chidiac , Radwan Massoud, Mohamad Haidar, Ali Bazarbachi, Jean El Cheikh
14 (93)
Allogeneic
1 (7)
Frontline ABVD
-
Clinical Lymphoma, Myeloma & Leukemia September 2016
3 (20) 15 (100)
Autologous
Median (Range)
Medical Center, Beirut, Lebanon, Beirut, Lebanon
S68
12 (80)
Lines of treatment before BV
Bone Marrow Transplantation Program, American University of Beirut
Context: Brentuximab Vedotin (BV) is a chimeric anti CD30 IgG1 antibody, conjugated to synthetic antitubulin momomethyl auristatin. BV is approved for the treatment of classical HL in relapse either after autologous stem cell transplantation (ASCT) or after two lines of combination chemotherapy in transplant ineligible patients. The AETHERA trial revealed increased PFS when BV is used as maintenance therapy after ASCT. Objective: Compare the effectiveness of BV as maintenance or salvage therapy after ASCT for relapsed/refractory (R/R) HL. Design: A retrospective analysis conducted on patients with R/R HL treated with BV after ASCT either as maintenance or salvage therapy. Analysis after a median follow up of 12 months is reported. Setting: The study was conducted in a single institution; American University of Beirut Medical Center (AUBMC) after IRB approval. Patients: The study included 15 adult patients with R/R HL treated with BV with the following indications: Maintenance therapy after ASCT in high risk patients Salvage therapy for relapse after ASCT or allo-SCT Intervention: BV at 1.8mg/kg IV every 4 weeks for the above indications. Main Outcome Measures: response rate (RR), overall survival (OS) and progression free survival (PFS). Results: Nine high-risk patients (60%) received 4 cycles of BV as maintenance therapy post ASCT. Six additional patients (40%) in relapse after ASCT (n¼5) or after allo-SCT (n¼1) received BV as salvage therapy for an average of 4 cycles (range 3-21). Patients characteristics are listed on Table 1. RR was 33% in 6 patients who received BV as salvage post SCT. Two patients proceeded with allo-SCT in
29 (20-61)
Gender
Primary Refractory Responded Unknown
3 (2-6) 15 (100) 2 (13) 10 (67) 3 (20)
BV initiation As maintenance post auto-SCT
9 (60)
Salvage for post transplant relapse
6 (40)
HL-182 Differences in Outcome of Patients with Syncytial Variant Hodgkin Lymphoma (HL) Compared with Typical Nodular Sclerosis HL Tarsheen Sethi ,1 Van Nguyen,2 Shaoying Li,3 David Morgan,1 John Greer,1 Nishitha Reddy1 1
Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States; 2
Department of Medicine, Vanderbilt University Medical Center,
Nashville, TN, United States; 3Department of Hematopathology, MD Anderson Cancer Center, Houston, TX, United States
Introduction: Syncytial variant of nodular sclerosis HL (SV) is a well described pathologic entity characterized by prominent aggregates of Hodgkin/Reed Sternberg cells in nodules separated by
Abstracts fibrous collagen bands. Little is known regarding the clinical behavior of the SV. We systematically studied the clinical features and outcome of patients with SV and further compared them with patients with typical nodular sclerosis HL (t-NS). Patients and Methods: 167 adult patients (pts.) with Nodular Sclerosis HL were included in our analysis following institutional IRB approval. Differences between SV vs. t-NS were analyzed using Chi-square and t Student tests. Kaplan Meier method was used to calculate the Progression free survival (PFS) and overall survival (OS). Log rank test was used to determine the differences in survival. Results: 43 were confirmed as SV based on morphology and immunophenotype. The median age at diagnosis was 31 yrs. (range: 18-75yrs.) and 85 patients were male (51%). 100% patients had an ECOG status of 0-1; 39 % had advanced stage disease (stage III and IV); and 48% had B symptoms. 23 % patients presented with bulky disease. 90% patients received ABVD as their initial treatment. The remaining were treated with Stanford V, MOPP or on a clinical trial. 37% patients received radiation therapy. In the SV vs. t-NS comparison, no statistically significant differences were observed between the two groups with regards to age, gender, stage at presentation, B symptoms, bulky disease or favorable features. The rate of complete response (CR) in the SV group was 74% vs. 87% in the t-NS group (P¼0.05). Moreover, at a median follow up of 49 months, the median progression free survival (PFS) was inferior in the SV group (17.02 months) compared with the t-NS group (not reached) (P<0.0001; HR ¼ 3.695; 95% CI¼3.0-11.07). The median overall survival (OS) was not reached in both groups and was not statistically different [P¼0.32]. Discussion: In summary, our results suggest that SV was associated with a lower rate of complete response and inferior PFS. These patients can be salvaged with standard salvage regimens, ASCT or newer immunomodulatory agents and therefore OS is not compromised.
Multiple Myeloma
MM-015 High-Density Neutrophils are Immunosuppressive in Multiple Myeloma Due to Increased Arginase-1, Predictor of Short Progression Free Survival Alessandra Romano ,1,2 Manteiga Jose,2,3 Vittorio Simeon,4 Nunziatina Parrinello,1 Cesarina Giallongo,1 Piera La Cava,1 Giuseppina Rizzo,1 Concetta Conticello,1 Maria Consoli,1 Daniele Tibullo,1 Lorenzo Canziani,2 Francesca Fontana,2 Pellegrino Musto,4 Simone Cenci,2 Francesco Di Raimondo1 1
Division of Hematology, AOUP Vittorio Emanuele, University of Cat-
ania, Catania, Italy; 2Age Related Disease Unity, Fondazione Centro San Raffaele, Milano, Italy; 3Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy; 4Laboratory of Pre-clinical and TranslationalResearch IRCCS - CROB Referral Cancer Center of Basilicata, Rionero in Vulture (PZ), Italy
Context: In Multiple Myeloma (MM), granulocytic myeloid derived suppressor cells (G-MDSC) have a pivotal role in the interaction between the host immune system and plasma-cells (PC) proliferation. However, it is hard distinguishing G-MDSC from other neutrophil subpopulations, such as mature high-density neutrophils (HDN). Objective: Investigate the role of the mature myeloid component in MM, focused on the function of HDN, not included by MDSC definition. Design: Since functional activity and the immunophenotype changes occurring in MM-HDN could be recapitulated in vitro after exposure of healthy HDN to MM sera, we investigated i) HDN gene-expression profile (GEP) and ii) metabolomic profile, in order to identify metabolites and enzymes involved in myeloid-driven immunosuppression. Participants: Functional essays involved HDN sorted from 60 newly-diagnosed MM, 30 MGUS and 30 healthy subjects from AOUP (Catania, Italy). For technical issues, GEP was limited to 5 MM and 3 healthy subjects. For metabolomics, an independent series of 167 samples of BM and peripheral plasma were collected ad hoc at FCSR (Milano, Italy) from 125 individuals, comprising newly diagnosed MM (n¼16), relapsing or progressive disease (n¼20), clinical remission (n¼13), MGUS (n¼30), SM (n¼17) and age-matched healthy volunteers (n¼29). Main Outcomes Measures: Progression free survival in newly-diagnosed MM patients was evaluated based of endpoints related to myeloid-driven suppression. Results: In cocultures with allogeneic T-cells, immunosuppressive ability of MMHDN could be reverted by exposure to nor-NOHA, a selective inhibitor of Arg-1. Both -omic approaches converged on the same pathways of immunosuppression regulated by Arginase-1 (Arg-1) and indoleamine 2,3-dioxygenase (IDO). Indeed, Arg-1 was among the ten genes increased in MM, while arginine and tryptophan were among the metabolites differentially reduced in MM. These
Clinical Lymphoma, Myeloma & Leukemia September 2016
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the salvage group. After a median follow up of 9 months, only 2 patients (22%) in the maintenance group progressed and all patients are still alive. Conversely, in the salvage group, 4 patients (67%) progressed and 1 patient developed secondary AML and died. Conclusion: BV therapy showed an efficacy only as maintenance treatment after auto-SCT but was less successful when used as post-transplant salvage in R/R HL. Four cycles of maintenance may suffice. Prospective trials with larger samples are warranted to support these findings. Table 1 Patients Characteristics Characteristics
N (%)
Age at BV initiation Median (range)
HL-160 Post Transplant Brentuximab Maintenance Appears more Effective than Post Transplant Salvage Brentuximab for Relapsed /Refractory Hodgkin Lymphoma
Male
9 (60)
Female
6 (40)
HL subtype Nodular Sclerosis Unknown Prior transplant
Amanda Chidiac , Radwan Massoud, Mohamad Haidar, Ali Bazarbachi, Jean El Cheikh
14 (93)
Allogeneic
1 (7)
Frontline ABVD
-
Clinical Lymphoma, Myeloma & Leukemia September 2016
3 (20) 15 (100)
Autologous
Median (Range)
Medical Center, Beirut, Lebanon, Beirut, Lebanon
S68
12 (80)
Lines of treatment before BV
Bone Marrow Transplantation Program, American University of Beirut
Context: Brentuximab Vedotin (BV) is a chimeric anti CD30 IgG1 antibody, conjugated to synthetic antitubulin momomethyl auristatin. BV is approved for the treatment of classical HL in relapse either after autologous stem cell transplantation (ASCT) or after two lines of combination chemotherapy in transplant ineligible patients. The AETHERA trial revealed increased PFS when BV is used as maintenance therapy after ASCT. Objective: Compare the effectiveness of BV as maintenance or salvage therapy after ASCT for relapsed/refractory (R/R) HL. Design: A retrospective analysis conducted on patients with R/R HL treated with BV after ASCT either as maintenance or salvage therapy. Analysis after a median follow up of 12 months is reported. Setting: The study was conducted in a single institution; American University of Beirut Medical Center (AUBMC) after IRB approval. Patients: The study included 15 adult patients with R/R HL treated with BV with the following indications: Maintenance therapy after ASCT in high risk patients Salvage therapy for relapse after ASCT or allo-SCT Intervention: BV at 1.8mg/kg IV every 4 weeks for the above indications. Main Outcome Measures: response rate (RR), overall survival (OS) and progression free survival (PFS). Results: Nine high-risk patients (60%) received 4 cycles of BV as maintenance therapy post ASCT. Six additional patients (40%) in relapse after ASCT (n¼5) or after allo-SCT (n¼1) received BV as salvage therapy for an average of 4 cycles (range 3-21). Patients characteristics are listed on Table 1. RR was 33% in 6 patients who received BV as salvage post SCT. Two patients proceeded with allo-SCT in
29 (20-61)
Gender
Primary Refractory Responded Unknown
3 (2-6) 15 (100) 2 (13) 10 (67) 3 (20)
BV initiation As maintenance post auto-SCT
9 (60)
Salvage for post transplant relapse
6 (40)
HL-182 Differences in Outcome of Patients with Syncytial Variant Hodgkin Lymphoma (HL) Compared with Typical Nodular Sclerosis HL Tarsheen Sethi ,1 Van Nguyen,2 Shaoying Li,3 David Morgan,1 John Greer,1 Nishitha Reddy1 1
Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States; 2
Department of Medicine, Vanderbilt University Medical Center,
Nashville, TN, United States; 3Department of Hematopathology, MD Anderson Cancer Center, Houston, TX, United States
Introduction: Syncytial variant of nodular sclerosis HL (SV) is a well described pathologic entity characterized by prominent aggregates of Hodgkin/Reed Sternberg cells in nodules separated by
Abstracts fibrous collagen bands. Little is known regarding the clinical behavior of the SV. We systematically studied the clinical features and outcome of patients with SV and further compared them with patients with typical nodular sclerosis HL (t-NS). Patients and Methods: 167 adult patients (pts.) with Nodular Sclerosis HL were included in our analysis following institutional IRB approval. Differences between SV vs. t-NS were analyzed using Chi-square and t Student tests. Kaplan Meier method was used to calculate the Progression free survival (PFS) and overall survival (OS). Log rank test was used to determine the differences in survival. Results: 43 were confirmed as SV based on morphology and immunophenotype. The median age at diagnosis was 31 yrs. (range: 18-75yrs.) and 85 patients were male (51%). 100% patients had an ECOG status of 0-1; 39 % had advanced stage disease (stage III and IV); and 48% had B symptoms. 23 % patients presented with bulky disease. 90% patients received ABVD as their initial treatment. The remaining were treated with Stanford V, MOPP or on a clinical trial. 37% patients received radiation therapy. In the SV vs. t-NS comparison, no statistically significant differences were observed between the two groups with regards to age, gender, stage at presentation, B symptoms, bulky disease or favorable features. The rate of complete response (CR) in the SV group was 74% vs. 87% in the t-NS group (P¼0.05). Moreover, at a median follow up of 49 months, the median progression free survival (PFS) was inferior in the SV group (17.02 months) compared with the t-NS group (not reached) (P<0.0001; HR ¼ 3.695; 95% CI¼3.0-11.07). The median overall survival (OS) was not reached in both groups and was not statistically different [P¼0.32]. Discussion: In summary, our results suggest that SV was associated with a lower rate of complete response and inferior PFS. These patients can be salvaged with standard salvage regimens, ASCT or newer immunomodulatory agents and therefore OS is not compromised.
Multiple Myeloma
MM-015 High-Density Neutrophils are Immunosuppressive in Multiple Myeloma Due to Increased Arginase-1, Predictor of Short Progression Free Survival Alessandra Romano ,1,2 Manteiga Jose,2,3 Vittorio Simeon,4 Nunziatina Parrinello,1 Cesarina Giallongo,1 Piera La Cava,1 Giuseppina Rizzo,1 Concetta Conticello,1 Maria Consoli,1 Daniele Tibullo,1 Lorenzo Canziani,2 Francesca Fontana,2 Pellegrino Musto,4 Simone Cenci,2 Francesco Di Raimondo1 1
Division of Hematology, AOUP Vittorio Emanuele, University of Cat-
ania, Catania, Italy; 2Age Related Disease Unity, Fondazione Centro San Raffaele, Milano, Italy; 3Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy; 4Laboratory of Pre-clinical and TranslationalResearch IRCCS - CROB Referral Cancer Center of Basilicata, Rionero in Vulture (PZ), Italy
Context: In Multiple Myeloma (MM), granulocytic myeloid derived suppressor cells (G-MDSC) have a pivotal role in the interaction between the host immune system and plasma-cells (PC) proliferation. However, it is hard distinguishing G-MDSC from other neutrophil subpopulations, such as mature high-density neutrophils (HDN). Objective: Investigate the role of the mature myeloid component in MM, focused on the function of HDN, not included by MDSC definition. Design: Since functional activity and the immunophenotype changes occurring in MM-HDN could be recapitulated in vitro after exposure of healthy HDN to MM sera, we investigated i) HDN gene-expression profile (GEP) and ii) metabolomic profile, in order to identify metabolites and enzymes involved in myeloid-driven immunosuppression. Participants: Functional essays involved HDN sorted from 60 newly-diagnosed MM, 30 MGUS and 30 healthy subjects from AOUP (Catania, Italy). For technical issues, GEP was limited to 5 MM and 3 healthy subjects. For metabolomics, an independent series of 167 samples of BM and peripheral plasma were collected ad hoc at FCSR (Milano, Italy) from 125 individuals, comprising newly diagnosed MM (n¼16), relapsing or progressive disease (n¼20), clinical remission (n¼13), MGUS (n¼30), SM (n¼17) and age-matched healthy volunteers (n¼29). Main Outcomes Measures: Progression free survival in newly-diagnosed MM patients was evaluated based of endpoints related to myeloid-driven suppression. Results: In cocultures with allogeneic T-cells, immunosuppressive ability of MMHDN could be reverted by exposure to nor-NOHA, a selective inhibitor of Arg-1. Both -omic approaches converged on the same pathways of immunosuppression regulated by Arginase-1 (Arg-1) and indoleamine 2,3-dioxygenase (IDO). Indeed, Arg-1 was among the ten genes increased in MM, while arginine and tryptophan were among the metabolites differentially reduced in MM. These
Clinical Lymphoma, Myeloma & Leukemia September 2016
- S69