Sessions are scheduled in Singapore Time (SGT)
- Michelle Poon (Singapore, Singapore)
- Yong Sheng Jason Chan (Singapore, Singapore)
204MO - Patterns of treatment and outcomes in CLL patients in Australia: An analysis of the population-wide pharmaceutical benefits scheme dataset
- Constantine Tam (Melbourne, VIC, Australia)
Abstract
Background
There is limited information on the chronic lymphocytic leukaemia (CLL) patient characteristics and outcomes, or the treatment strategies adopted for its management in the Australian real-world setting. This study aimed to describe the treatment patterns and outcomes of people with CLL who received treatment under the Pharmaceutical Benefits Scheme (PBS).
Methods
This retrospective study included patients who initiated CLL treatment between 2011/01/01 and 2021/07/31 with data extracted from the 10% PBS dataset. The dataset contains the dispensing records for 10% of the Australian population and captures all publicly funded treatments. Outcomes of interest were treatment patterns, duration of therapy, time to next treatment (TTNT), and overall survival (OS). The first medication used for CLL was designated as the index date. The Kaplan-Meier (KM) method was used to analyse the duration of therapy, TTNT and OS. The effects of baseline patient characteristics and comedications were explored with sub-group sensitivity analyses and Cox proportional hazards regression analyses wherever feasible.
Results
Of 803 CLL patients included, most patients were male (65%) and >60 years (77%). Treatment trends have changed over the last 10 years. In the frontline setting, fludarabine-chlorambucil-rituximab use has decreased while chlorambucil + CD20 agents usage has increased. In the relapsed/refractory (R/R) setting, CD20 monotherapy has decreased and BTKi and venetoclax ± CD20 usage has increased. In the overall cohort, the median TTNT was 30 months (95%CI, 25-35). The median duration of ibrutinib therapy was 24 months (95%CI, 19-38) and 19 months (95%CI, 11-not reached (NR)) for venetoclax. Median OS was 127 (95%CI, 105-NR) and 94 months (95%CI, 74-NR) in front-line and R/R patients respectively. For the sub-cohort with R/R CLL initiating treatment after Nov 2017 (the first BTKi listing on the PBS) (n=114), the median OS was not reached yet.
Conclusions
In the Australian setting, CLL treatment patterns have significantly changed since the introduction of novel therapies. Median OS in the front-line setting is more than 10 years, while the R/R population has a shorter OS observed.
Legal entity responsible for the study
BeiGene.
Funding
BeiGene.
Disclosure
C. Tam: Financial Interests, Personal, Advisory Role: BeiGene; Financial Interests, Personal, Other, Honoraria: AbbVie, Janssen, BeiGene; Financial Interests, Institutional, Research Grant: AbbVie, Janssen, BeiGene. F. Zhao, R. Gauba, B. Tang: Financial Interests, Institutional, Full or part-time Employment: BeiGene; Financial Interests, Institutional, Stocks/Shares: BeiGene. M.H. Kouhkamari: Financial Interests, Institutional, Full or part-time Employment: Prospection; Financial Interests, Institutional, Other, Consulting, Prospection is a consulting service provider: Pharma companies in Australia. S.C. Li: Financial Interests, Personal, Advisory Role: BeiGene.
205MO - Patterns of treatment and outcomes in MCL patients in Australia: An analysis of the population-wide pharmaceutical benefits scheme dataset
- Constantine Tam (Melbourne, VIC, Australia)
Abstract
Background
There is limited information on the patient characteristics and outcomes of people with mantle cell lymphoma (MCL), or the treatment strategies adopted to their management in the Australian real-world setting. The purpose of this study was to describe the treatment patterns and outcomes of people with MCL who receive treatment under the Australian Pharmaceutical Benefits Scheme (PBS).
Methods
This retrospective study included patients who initiated treatment for MCL between 2011/01/01 and 2021/07/31 with data extracted from the 10% PBS dataset. This dataset contains the dispensing records for 10% of the Australian population and captures all publicly funded treatments in Australia. Outcomes of interest were treatment patterns, duration of therapy, time to next treatment (TTNT), and overall survival (OS). The date of the first medication used for MCL was designated as the index date. The Kaplan-Meier (KM) method was used to analyse the duration of therapy, TTNT, and OS. The effects of baseline patient characteristics and comedications were explored with sub-group sensitivity analyses and Cox proportional hazards regression analyses wherever feasible.
Results
There were 152 patients with MCL included. Most patients were male (68%) and >60 years of age (85%). Treatment trends have changed over the last 10 years. In the front-line setting bendamustine-rituximab (B-R) is now the major regimen used whereas previously rituximab was more commonly used in combination with other agents. In the relapsed/refractory (R/R) setting, the Bruton’s tyrosine kinase inhibitor BTKi (ibrutinib) has replaced the use of rituximab monotherapy or rituximab combinations. In the overall cohort, the median TTNT was 18 months (95%CI, 10-32). The median duration of ibrutinib therapy was 6 months (95%CI, 5-20) and 38.20% of patients was continuing treatment at 12 months. Median OS was 92 (95%CI, 72- not reached (NR)), and 84 months (95% CI, 56-NR), in front-line and R/R patients, respectively.
Conclusions
In the Australian setting, MCL treatment patterns have significantly changed since the introduction of novel agents, including BTKis. Median OS in the front-line setting is more than 7 years.
Legal entity responsible for the study
BeiGene.
Funding
BeiGene.
Disclosure
C. Tam: Financial Interests, Personal, Advisory Role: BeiGene; Financial Interests, Personal, Other, Honoraria: AbbVie, Janssen, BeiGene; Financial Interests, Institutional, Research Grant: AbbVie, Janssen, BeiGene. F. Zhao, R. Gauba, B. Tang: Financial Interests, Personal, Full or part-time Employment: BeiGene; Financial Interests, Personal, Stocks/Shares: BeiGene. S. Azam: Financial Interests, Personal, Full or part-time Employment: Prospection; Financial Interests, Institutional, Other, Contulting, Prospection is a consulting service provider: Pharma companies in AU. S.C. Li: Financial Interests, Personal, Advisory Role: BeiGene.
206MO - Treatment patterns in patients with mantle cell lymphoma: Report of the Asia-Pacific multinational retrospective registry study
- Hyungwoo Cho (Seoul, Korea, Republic of)
Abstract
Background
To better define the clinical characteristics, treatment patterns, and survival outcomes of patients with mantle cell lymphoma (MCL), we conducted a multinational retrospective registry study for newly diagnosed patients with MCL.
Methods
Clinical and laboratory data were collected from newly diagnosed MCL patients between January 2008 and December 2017 from 16 hospitals in South Korea, two in Malaysia, and one in Taiwan.
Results
A total of 191 patients with MCL were enrolled in this retrospective registry study. The median age was 66 years (range, 38–90), and majority of the patients had advanced stage disease (n = 150, 83.8%). The most frequently administered 1st line regimen was R-CHOP like regimen (n = 117, 61.3%), followed by cytarabine containing regimen (n = 41, 21.5%). There was a significant difference in the treatment pattern between young (age < 65, n = 90) versus elderly patients (age ≥ 65, n = 101). Higher proportion of elderly patients received R-CHOP like regimen as 1st line regimen compared with young patients (72.3% vs. 48.9%), while cytarabine containing regimen was more frequently administered in young patients (38.9% vs, 5.9%). The treatment response to 1st line regimens were available in 176 patients. The overall response rate (ORR) and the complete response (CR) rate among these patients were 94.9% (n = 167) and 52.3% (n = 92), respectively. A total of 106 patients were treated with 2nd line regimen. The most frequently administered 2nd line regimen was ibrutinib (n = 29, 27.4%) and cytarabine based regimen (n = 29, 27.4%), followed by BR (n = 12, 11.3%). The treatment response to 2nd line regimens were available in 89 patients, and the ORR and the CR rate among these patients were 74.2% (n = 66) and 38.2% (n = 34), respectively. Survival outcomes will be updated and presented at the ESMO Asia Congress 2022.
Conclusions
The current study offers an opportunity to better understand the treatment patterns of patients with MCL in the Asia-Pacific region. The most commonly used 1st line regimen was R-CHOP like regimen. Ibrutinib and cytarabine based regimen were the most frequently administered 2nd line regimens.
Legal entity responsible for the study
The authors.
Funding
The work was funded by a research grant from Janssen Pharmaceuticals Ltd.
Disclosure
All authors have declared no conflicts of interest.
207MO - Efficacy and safety of IMC-001, anti-PD-L1 antibody, in patients with relapsed or refractory extranodal NK/T cell lymphoma, nasal type (R/R ENKTL)
- Won Seog Kim (Seoul, Korea, Republic of)
Abstract
Background
ENKTL is a rare EBV associated lymphoma with high immunogenicity, and the prognosis of R/R ENKTL is extremely poor when asparaginase-based therapy fails. There is no standard treatment, and the clinically unmet demand is so high that new effective treatments are urgently needed. Small studies using PD-1/PD-L1 inhibitors for ENKTL treatment showed varying anti-tumor activity. IMC-001 is a fully human IgG1 monoclonal antibody that binds to human PD-L1 to enhance T cell activation and retains Fc effector function to stimulate antibody-dependent cell-mediated cytotoxicity. We present efficacy and safety of the phase 2 study of IMC-001 in patients with R/R ENKTL.
Methods
Patients with histologically confirmed ENKTL who failed to at least one prior therapy including asparaginase-based regimen were enrolled. Patients received IMC-001 20 mg/kg intravenously every two weeks for up to 2 years until disease progression or unacceptable toxicity. The primary endpoint is the objective response rate (ORR) determined by centralized independent assessment per the Lugano criteria with LYRIC modification for lymphoma.
Results
Between October 2020 and June 2022, 13 patients were enrolled and currently 8 patients are receiving treatment. The median age was 59 years (range 46-79), 11 (85%) were male. 6 patients (46%) had an ECOG performance status of 1. Median number of prior systemic therapy was 2 (range 1-4). 9 patients (69%) received radiotherapy. Of the 5 efficacy-evaluable patients, 4 patients had a complete response (CR) and an ORR of 80%. All the patients with CR have continued treatment for at least 1 year. Most treatment-emergent AEs (TEAEs) were grade 1-2, and no grade 3 or more TEAE was observed. The most common AE was fatigue. No TEAEs or serious AEs that resulted in the treatment discontinuation or death. Grade 2 infusion-related reactions (IRR), grade 2 uveitis, and grade 2 hypothyroidism suspected to related to IMC-001 were observed in 1 patient each.
Conclusions
PD-L1 blockade with IMC-001 is highly effective in patients with R/R ENKTL failing L-asparaginase regimens. IMC-001 has a good safety profile without long-term toxicity. We will present updated data for efficacy, safety, and biomarker.
Clinical trial identification
NCT04414163.
Legal entity responsible for the study
ImmuneOncia Therapeutics, Inc.
Funding
ImmuneOncia Therapeutics, Inc.
Disclosure
W.S. Kim: Financial Interests, Personal, Advisory Board: Immuneoncia Therapeutics. J. Oh, J.H. Lee, H.T. Kim: Financial Interests, Personal, Full or part-time Employment: Immuneoncia Therapeutics. All other authors have declared no conflicts of interest.
Invited Discussant 204MO, 205MO, 206MO and 207MO
- Yong Sheng Jason Chan (Singapore, Singapore)
Q&A and discussion
- Michelle Poon (Singapore, Singapore)
208MO - Immune related adverse events and biomarkers after Anbal-cel, novel anti-CD19 CAR-T therapy with dual silencing of PD-1 and TIGIT: Updates from phase I study
- Won Seog Kim (Seoul, Korea, Republic of)
Abstract
Background
Anbal-cel is a novel 2nd generation autologous CD19 CAR-T cell therapy which has been knock-downed for PD-1 and TIGIT using OVIS platform and demonstrated the superior T-cell functionality compared with CD19 CAR-T cells at preclinical studies.
Methods
This Phase 1 dose escalation part was evaluated for the safety and preliminary efficacy in patients with r/r LBCL. Anbal-cel was administered at dose level 1 (2x105 cells/kg), DL2 (7x105 cells/kg) or DL3 (2x106 cells/kg). Blood samples have been collected to assess PK, cytokine levels, immune phenotypes and safety etc.
Results
As of May 25 2022, 11 patients with r/r DLBCL were infused with Anbal-cel; 4pts at DL1, 3pts at DL2 and 4pts at DL3. Median manufacturing time was 8 days (range 5-11) and median CD4:CD8 ratio of final product was 1.1. Median knock-down rate of PD-1 and TIGIT was 65% and 96% respectively. Complete response rate was 82% (9/11) and CAR genes were detectable at 6 months in 4 out 5 evaluable patients by qPCR method. Of 11 patients, 5 (45%) experienced CRS with median onset time of 7 days (range 1-16) and median duration of 5 days (range 1-19) and 2 (18%) experienced grade 3 CRS. One patient dosed at DL3 experienced grade 2 ICANS. Grade ≥3 Anemia, neutropenia and thrombocytopenia at day 28 was observed at 22%, 82%, 55% respectively and incidence of grade ≥3 cytopenia was correlated with the dose of Anbal-cel. The Peak levels of IL-2, 6, 8, 10, TNF-α and MCP-1 were increased proportionally to the dose of Anbal-cel while the peak of IFN-γ ramined indifferent depending on the dose of Anbal-cel. B-cell aplasia was maintained from all responding patients by flow cytometry except for one patient at DL2 whose B-cell was reappeared at 3 months and documented PD at 5 months after achieving CR. LDH and CRP changes were inversely proportional to the dose of Anbal-cel but Ferritin level wasn't found to be related to the dose of Anbal-cel.
Conclusions
Anbal-cel expanded proportionally to the infused dose and cytokines were increased in response to the level of Anbal-cel expanded. Concurrent with the increased Anbal-cel expansion and cytokine levels, prolonged cytopenia was observed in dose responsive manner and these are planned to be further investigated in phase 2.
Clinical trial identification
CRC01-01 (NCT04836507).
Legal entity responsible for the study
Curocell Inc.
Funding
Curocell Inc.
Disclosure
J. Kim: Financial Interests, Institutional, Full or part-time Employment: Curocell. All other authors have declared no conflicts of interest.
209MO - Impact of CMV reactivation on survival and relapse following allogeneic stem cell transplantation for de novo myeloid sarcoma
- Benjamin J. McCormick (Mobile, United States of America)
Abstract
Background
Cytomegalovirus reactivation (CMV-R) following allogenic hematopoietic stem cell transplantation (allo-HCT) is a common complication with conflicting clinical impact. Prior studies have linked CMV-R to increased mortality after allo-HCT; however, prior studies linked CMV-R to decreased risk of relapse. We present survival outcomes related to CMV-R in 37 patients with de novo myeloid sarcoma (MS) treated with allo-HCT.
Methods
In this retrospective study, we analyzed medical records of adult patients with de novo MS who received allo-HCT at Mayo Clinic between 1996 and 2021. Survival outcomes were analyzed using Kaplan-Meier and Cox-proportional hazard models for univariate and multivariate analysis, respectively. CMV was identified via quantitative polymerase chain reaction in serum samples with reactivation defined as >500 CMV copies/mL.
Results
We identified 37 patients at Mayo Clinic who received allo-HCT for de novo MS. Isolated MS (iMS) without bone marrow involvement was observed in 38% patients, whereas 62% presented with synchronous MS (sMS) with bone marrow involvement. CMV-R occured in 39% previously CMV seropositive patients after allo-HCT, including 2 patients with iMS and 7 with sMS. Across all patients, median overall survival (mOS) was significantly lower at 13.7 months in patients with CMV-R versus 36.3 months without CMV-R (p=0.03). CMV-R was associated with increased mortality when adjusted for age and genomic risk stratification [HR 2.5; 95% CI: 1.05-6.17 (p=0.04)]. In sMS, CMV-R was associated with lower mOS at 13.7 months versus 36.3 months without CMV-R (p=0.03). Immunosuppression regimen did not impact incidence of CMV-R. The relapse rate after allo-HCT was 33% in patients with CMV-R versus 37% without CMV-R (p=1.0).
Conclusions
De novo MS is a rare form of AML with limited evidence to guide therapies. Given that many centers use CMV serostatus to guide donor selection, we sought to characterize the impact of CMV-R in allo-HCT in MS. In sMS, CMV-R was associated with decreased mOS by almost two years. CMV-R in iMS did not impact survival, although limited by small sample size. Effective CMV prophylaxis following allo-HCT can reduce mortality and improve survival outcomes in MS.
Legal entity responsible for the study
Mayo Clinic.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant 208MO and 209MO
- Michelle Poon (Singapore, Singapore)
Q&A and discussion
- Michelle Poon (Singapore, Singapore)