Challenges in Global Access to CAR-T cells: an Asian Perspective.

The use of cell therapy for clinical applications has seen a dramatic increase in recent years, primarily in oncology, especially with the use of chimeric antigen receptor (CAR) T-cell therapies. However, there are some barriers to the widespread adoption of CAR-T cell therapies globally, primarily because of the high cost of manufacturing these cells and clinical infrastructure considerations. We reviewed the different strategies adopted across Asia to implement CAR-T cell therapy and found that these included patient assistance programs, close engagement with funders, cost-effectiveness studies, on-site manufacturing of CAR-T cells, and joint ventures between local partners and foreign pharmaceutical companies. Although on-site manufacturing can reduce the cost of genetic engineering and expansion, it does not address many other hidden costs and quality considerations. Future growth in large-scale regional manufacturing, facilitated by cutting-edge science and innovation, could reduce costs through economies of scale and facilitate the eagerly needed global access.

Asia-Pacific Leukemia Consortium: An innovative and collaborative initiative to improve care of leukemia and related diseases in the Asia-Pacific region.

The burden of leukemia and related diseases is rapidly growing in Asia. Currently, there is a paucity of regional collaborative groups/initiatives that focus exclusively on the management of leukemia in the Asia-Pacific (APAC) region. The Asia-Pacific Leukemia Consortium (APLC) was established on the 8 September 2021 to understand the status quo, unmet needs, and ways to improve the management of leukemia and related diseases in the APAC region. The APLC working group set up a group of experts from various countries (Singapore, Malaysia, Thailand, Hong Kong, Japan, South Korea, Taiwan, China, and Australia) to discuss on the status of: (i) clinical trials; (ii) disease registry database; (iii) genetic and tissue repository; (iv) patient advocacy and care; and (v) disease prevention and education in the APAC region. Low levels of awareness about leukemia amongst the public, lack of financial support, and limited access to newly approved therapies were identified as barriers to the implementation of effective leukemia management in low- or mid-income Asian countries. Patients often enroll in clinical trials to gain access to novel/approved therapies. The APLC group aims to address the growing threat of leukemia through a collaborative approach to advance disease prevention, research, clinical trials, and education.

Expert consensus on the management of chronic lymphocytic leukaemia in Asia.

In recent years, considerable progress has been made in the standard treatment for chronic lymphocytic leukaemia (CLL) due to the availability of new potent drugs. However, the majority of data on CLL were derived from Western populations, with limited studies and guidelines on the management of CLL from an Asian population perspective. This consensus guideline aims to understand treatment challenges and suggest appropriate management approaches for CLL in the Asian population and other countries with a similar socio-economic profile. The following recommendations are based on a consensus by experts and an extensive literature review and contribute towards uniform patient care in Asia.

Real-world multicenter study of the safety and efficacy of netupitant plus palonosetron fixed-dose combination to prevent chemotherapy-induced nausea and vomiting among Malaysian patients receiving moderately or highly emetogenic chemotherapy.

AIM: A large proportion of cancer patients are at high risk for chemotherapy-induced nausea and vomiting (CINV), but the choice of anti-emetics for CINV in Malaysia is limited. METHODS: This was a real-world study of a fixed-dose combination of netupitant and palonosetron (NEPA) to inhibit CINV in adult patients receiving moderately (MEC) or highly emetogenic chemotherapy (HEC) for solid/hematological malignancies at eight Malaysian centers. Each HEC/MEC cycle received one dose of NEPA + dexamethasone for CINV prevention. Complete response (no emesis, no rescue medication) (CR), no more than mild nausea (severity score ≤ 2.5), and complete control (CR) (no more than mild nausea) during the acute (0-24 h), delayed (25-120 h), and overall (0-120 h) phases post-chemotherapy were measured. Treatment-related adverse events (AEs) were recorded. RESULTS: During March 2016-April 2018 (NMRR-17-3286-38282), NEPA + dexamethasone was administered to 54 patients (77.8% solid, 22.2% hematological malignancies). Note that 59.3% received HEC, while 40.7% received MEC regimen. During the overall phase of the first cycle, the majority had CR (77.8%), no more than mild nausea (74.1%), and complete control (61.1%). Seventeen patients received two consecutive cycles at any point of chemotherapy cycles. During the overall phases across two consecutive cycles, all patients achieved CR, and the majority reported no more than mild nausea and complete control. No grades 3-4 AEs were reported. CONCLUSIONS: NEPA had sustained efficacy and tolerability at first administration and across two cycles of MEC/HEC for CINV prevention.

Cutaneous T-cell lymphoma in Asian patients: a multinational, multicenter, prospective registry study in Asia.

Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0-122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3-4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs.

Comprehensive analysis of peripheral T-cell and natural killer/T-cell lymphoma in Asian patients: A multinational, multicenter, prospective registry study in Asia.

BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are uncommon and their frequency is regionally heterogeneous. Several studies have been conducted to evaluate the clinical features and treatment outcomes of this disease entity, but the majority of these were conducted in limited areas, making it difficult to comprehensively analyze their relative frequency and clinical features. Furthermore, no consensus treatment for PTCLs has been established. Therefore, we conducted an Asia-specific study to understand the relative frequency of PTCLs and assess treatments and their outcomes in Asian patients. METHODS: We performed a multinational, multicenter, prospective registry of adult patients with PTCLs that was named as the International Cooperative non-Hodgkin T-cell lymphoma prospective registry study where thirty-two institutes from six Asian countries and territories (Korea, China, Taiwan, Singapore, Malaysia, and Indonesia) participated. FINDINGS: A total of 486 patients were registered between April 2016 and February 2019, and more than a half of patients (57%) had stage III or IV. Extranodal natural killer (NK)/T- cell lymphoma was the most common subtype (n = 139,28.6%), followed by angioimmunoblastic T-cell lymphoma (AITL, n = 120,24.7%), PTCL-not otherwise specified (PTCL-NOS, n = 101,20.8%), ALK-positive anaplastic large cell lymphoma (ALCL, n = 34,6.9%), and ALK-negative ALCL (n = 30,6.2%). The median progression-free survival (PFS) and overall survival (OS) were 21.1 months (95% CI,10.6-31.6) and 83.6 months (95% CI, 56.7-110.5), respectively. Upfront use of combined treatment with chemotherapy and radiotherapy showed better PFS than chemotherapy alone in localized ENKTL whereas consolidation with upfront autologous stem cell transplantation (SCT) provided longer PFS in advance stage ENKTL. In patients with PTCLs other than ENKTL, anthracycline-containing chemotherapies were widely used, but the outcome of those regimens was not satisfactory, and upfront autologous SCT was not significantly associated with survival benefit, either. The treatment outcome of salvage chemotherapy was disappointing, and none of the salvage strategies showed superiority to one another. INTERPRETATION: This multinational, multicenter study identified the relative frequency of each subtype of PTCLs across Asian countries, and the survival outcomes according to the therapeutic strategies currently used. FUNDING: Samsung Biomedical Research Institute.

Outcomes of high dose therapy and autologous haematopoietic stem cell transplantation for non-hodgkin lymphoma: A retrospective analysis in a resource-limited country.

AIM: To retrospectively report the clinical outcomes of non-Hodgkin's Lymphoma (NHL) patients post high dose therapy (HDT) with autologous haematopoietic stem cell transplant (AHSCT) and determine whether upfront transplant, which is a first-line consolidative treatment with induction chemotherapy, would be a feasible modality in a resource-limited country. METHODS: The medical records for NHL patients who had undergone HDT followed by AHSCT from October 1997 to November 2016 from two hospitals in Klang Valley, Malaysia were obtained from the medical record database and analysed retrospectively through statistical analysis. RESULTS: A total of 148 patients were retrospectively identified post-AHSCT, where the majority of whom had B cell lymphoma (53.4%). Majority of patients (88.5%) were in complete remission before AHSCT. The overall survival (OS) and event-free survival (EFS) at 3 years were 68.9% and 60.8%, respectively. The major cause of death was disease progression at 73.9%, while transplant-related mortality was 15.2%, with a median follow-up period of 179.5 weeks. CONCLUSION: Our study illustrates the promising outcomes of HDT with AHSCT in NHL patients in a resource-limited country. We recommend larger studies to be conducted in the future with a longer duration of follow-up to validate our findings.

Panobinostat in combination with bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma: an open-label, multicentre phase 2 trial.

BACKGROUND: Patients with relapsed or refractory peripheral T-cell lymphoma have a poor prognosis after conventional chemotherapy. Approved novel agents have only modest single-agent activity in most subtypes of peripheral T-cell lymphoma. Panobinostat is a potent oral pan-deacetylase inhibitor. Findings of many preclinical studies have shown synergistic antilymphoma activity when panobinostat is combined with the proteasome inhibitor bortezomib. We aimed to study the effect of panobinostat and bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma. METHODS: In this open-label, multicentre phase 2 trial, we recruited patients aged 21 years or older with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy from five tertiary hospitals in Singapore, Malaysia, and South Korea. Patients received 20 mg oral panobinostat three times a week and 1·3 mg/m(2) intravenous bortezomib two times a week, both for 2 of 3 weeks for up to eight cycles. The primary endpoint was the proportion of patients who achieved an objective response in accordance with the International Working Group revised response criteria; analyses were by intention to treat. The study is completed and is registered with ClinicalTrials.gov, number NCT00901147. FINDINGS: Between Nov 9, 2009, and Nov 26, 2013, we enrolled 25 patients with various histological subtypes of peripheral T-cell lymphoma. Of 23 patients assessable for responses, ten (43%, 95% CI 23-63) patients had an objective response, of which five were complete responses. Serious adverse events were reported in ten (40%) of 25 patients. Common treatment-related grade 3-4 adverse events included thrombocytopenia (17 [68%]), neutropenia (ten [40%]), diarrhoea (five [20%]), and asthenia or fatigue (two [8%]). We recorded peripheral neuropathy of any grade in ten (40%) patients. INTERPRETATION: Combined proteasome and histone deacetylase inhibition is safe and feasible and shows encouraging activity for patients with peripheral T-cell lymphoma. Our findings validate those of preclinical studies showing synergism in the combination and represent a rational way forward in harnessing the full potential of novel agents in peripheral T-cell lymphoma. FUNDING: Novartis Pharmaceuticals, Janssen Pharmaceuticals, and Singhealth Foundation.

Chronic myeloid leukemia in the Asia-Pacific region: current practice, challenges and opportunities in the targeted therapy era.

Chronic myeloid leukemia (CML) management varies across Asia due to disparities in affluence and healthcare provision. We surveyed CML management practice at 33 hospitals in 14 countries/regions to identify treatment challenges and opportunities for harmonization. Patients were generally treated according to international guidelines; however, tyrosine kinase inhibitors (TKIs) and molecular monitoring are inaccessible to many patients not covered by national insurance or eligible for subsidized treatment. Late diagnosis and suboptimal monitoring, often due to cost and accessibility issues, are challenges. Priorities for Asia include: extending accessibility to TKIs; specialist laboratory monitoring; and enriching data to support regional CML management guidelines.