A unique hub-and-spoke model to optimize patient management in lymphoma using novel chimeric antigen receptor-T cell therapy in Southeast and South Asia.

Novel therapeutic options for cancer offer hope for patients and their families, particularly when the cancer has not responded to established treatment regimens. The chimeric antigen receptor (CAR)-T cell therapeutic approach has changed the treatment paradigm for relapsed or refractory lymphoma, extending the capacity of the patient's own T cells to detect and eliminate cancer cells through genetic modification of T-cell surface receptors. The process of establishing treatment centers and developing clinical expertize in this novel treatment strategy is complex. Time, resources, and a commitment to focusing health budgets on a new area are required. Currently, Singapore is the only country in southeast and south Asia with market authorization of the CAR-T product, tisagenlecleucel. Availability of CAR-T treatment across international borders provides patients in neighboring countries with choice in therapeutic options. This paper describes the unique hub-and-spoke cross-border collaboration developed between Singapore and its neighbors to provide access to CAR-T cell therapy for patients with relapsed or refractory lymphoma. To date in 2022, four patients have been included in the CAR-T treatment cross-border collaboration. Their stay in Singapore has been about 2 months' duration, including the pre-treatment evaluation, apheresis, CAR-T cell infusion and post-treatment monitoring. Patient support from referring and treating physicians, critical to the success of the undertaking, is characterized by early communication, patient selection, multi-disciplinary care, post-treatment monitoring, and attention to detail. The patient journey and the development and implementation of this unique collaboration are discussed.

A unique hub-and-spoke model to optimize patient management in lymphoma using novel CAR-T cell therapy in Southeast and South Asia.

Novel therapeutic options for cancer offer hope for patients and their families, particularly when the cancer has not responded to established treatment regimens. The CAR-T cell therapeutic approach has changed the treatment paradigm for relapsed or refractory lymphoma, extending the capacity of the patient's own T cells to detect and eliminate cancer cells through genetic modification of T-cell surface receptors. The process of establishing treatment centers and developing clinical expertize in this novel treatment strategy is complex. Time, resources, and a commitment to focusing health budgets on a new area are required. Currently, Singapore is the only country in southeast and south Asia with market authorization of the CAR-T product, tisagenlecleucel. Availability of CAR-T treatment across international borders provides patients in neighboring countries with choice in therapeutic options. This paper describes the unique hub-and-spoke cross-border collaboration developed between Singapore and its neighbors to provide access to CAR-T cell therapy for patients with relapsed or refractory lymphoma. To date in 2022, four patients have been included in the CAR-T treatment cross-border collaboration. Their stay in Singapore has been at least 2 months' duration, including the pre-treatment evaluation, apheresis, CAR-T cell infusion and post-treatment monitoring. Patient support from referring and treating physicians, critical to the success of the undertaking, is characterized by early communication, patient selection, multi-disciplinary care, post-treatment monitoring, and attention to detail. The patient journey and the development and implementation of this unique collaboration are discussed.

HEMATOPOIETIC STEM CELL TRANSPLANT IN AGGRESSIVE T AND NK/T CELL LYMPHOMA - ROLE OF UPFRONT AUTOLOGOUS TRANSPLANT IN NODAL PERIPHERAL T-CELL LYMPHOMA.

Aggressive T and NK/T-cell lymphoma are known to have a high risk of relapse and poor long-term prognosis. Hematopoietic stem cell transplantation has been performed as part of consolidation or salvage treatment. We retrospectively studied the outcomes of autologous (A) and allogeneic (allo) hematopoietic stem cell transplantation (SCT) in aggressive T and NK/T-cell lymphoma at our center between 2010 to 2020. Patients with nodal peripheral T-cell lymphoma (PTCL) that were younger than 65 years old who did not receive upfront autologous SCT (ASCT) at first complete remission were selected from our registry data for further comparison. Thirty-six patients underwent ASCT, and 16 patients underwent alloSCT. In the ASCT cohort, 18 patients with nodal PTCL who underwent upfront ASCT at first complete remission (upfront ASCT) were compared with 15 patients with nodal PTCL who were in first complete remission after single-line induction but did not receive ASCT. The two-year progression-free survival (PFS) and overall survival (OS) rates for the ASCT cohort were 58% and 73%, respectively. The two-year PFS and OS for the alloSCT cohort were 47% (P=0.35, P=0.02, respectively). Twenty-four patients who received SCT at first remission (21 ASCT and three alloSCT) had a two-year PFS and OS of 75% and 89%, respectively. In comparison, 28 patients who received SCT at relapse/refractory (15 ASCT and 13 alloSCT) had a two-year PFS and OS of 40% and 50%, respectively (P=0.047, P=0.024, respectively). Patients in complete remission prior to transplantation (n=42) had a two-year PFS and OS of 59% and 73%, respectively. In contrast, patients in partial remission prior to transplantation (n=10) had a two-year PFS and OS of 40% and 48%, respectively (p>0.05). Non-relapse mortality occurred in 6% and 43% of ASCT and AlloSCT, respectively. Multivariate analysis revealed that EBV-positivity at diagnosis indicated poorer PFS. EBV-positivity at diagnosis and more than two prior lines of treatment at transplant were associated with poorer OS. For nodal PTCL, the two-year PFS and OS were 79% and 100% for the upfront ASCT cohort and 78% and 92% for the non-upfront ASCT cohort, respectively (p>0.05). Hematopoietic SCT is a feasible treatment option for aggressive T and NK/T-cell lymphoma. Patients who underwent SCT at first remission had better survival rates than those who underwent SCT at relapse/refractory. Nevertheless, due to the limited sample size of the current study, the role of upfront ASCT in patients with nodal PTCL who achieved first complete remission remains unclear.

Nonhuman primate allogeneic hematopoietic stem cell transplantation by intraosseus vs intravenous injection: Engraftment, donor cell distribution, and mechanistic basis.

OBJECTIVE: The traditional intravenous (IV) route of administration for hematopoietic stem cell transplantation (HSCT) may result in inefficient placement of donor cells, possibly contributing to suboptimal engraftment and higher risk of graft-vs-host reactions. In order to perform detailed studies of engraftment and donor cell distribution in an animal model with anatomical similarity to man, we performed the first direct homing/engraftment efficiency comparison between intraosseus (IO) and IV HSCT in allogeneic nonhuman primate animal model to assess the utility and mechanism of donor cell homing after IO delivery. MATERIALS AND METHODS: Donor bone marrow (BM) cells labeled with PKH26 membrane dye were transplanted to nonmyeloablative-conditioned nonhuman primate animals. Chimerism was confirmed by polymerase chain reaction amplification of donor-specific short tandem repeat locus. RESULTS: Compared to the IO route, IV infusion trapped 2.4- to 4.8-fold more donor cells in peripheral organs, including the lung, heart, spleen, kidney, and liver. IO injection resulting in a 6.2-fold increase in donor cells retained in the BM at the site of injection and a 2.7-fold increase in donor cells retained in distant BM sites. A profile of selected cell adhesion molecules (CAMs) demonstrated that after IO HSCT, more donor cells express CAMs that could facilitate BM homing and redistribution to non-injection-side BM cavities. This change in homing efficiency may be clinically significant because IO transplantation in haploidentical recipients enhanced donor cell engraftment when compared to IV delivery. CONCLUSION: Our results suggest that IO injection enhances both homing and engraftment in nonhuman primate HSCT.