Author: Liu hailing, fan Lei
Author's unit: Jiangsu Provincial People's Hospital (the First Affiliated Hospital of Nanjing Medical University) source: the 61st American Society of Hematology (ash) of tumor information was held in Orlando, USA from December 7 to 10, 2019. [tumor information] Professor Fan Lei from Jiangsu People's Hospital (the First Affiliated Hospital of Nanjing Medical University) was specially invited to compile and comment on the important research report of T / NK cell lymphoma. Details are as follows.
Fan Lei, MD, chief physician, associate professor, deputy director of Hematology Department, Jiangsu People's Hospital
The first young executive director of China Anti Cancer Association
Vice chairman of the first youth committee of blood tumor Committee of China Anti Cancer Association
Member of blood tumor Committee of China Anti Cancer Association
Vice chairman of Youth Committee of blood branch of Jiangsu Medical Association
New York Presbyterian Hospital Affiliated to Columbia and Cornell University
The research direction is accurate diagnosis and treatment of lymphoid tumor
Liu Hailing
The first clinical medical college of Nanjing Medical University
Master of internal medicine (Hematology)
Abstract 466: cerdulatinib, a dual effect Syk / JAK inhibitor, is well tolerated and effective in recurrent / refractory peripheral T-cell lymphoma and cutaneous T-cell lymphoma
Research background
Clinical data show that Syk and JAK signaling pathway play an important role in the pathogenesis of peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). The dual inhibition of Syk and JAK may interfere with its multiple survival mechanism. The purpose of this study was to investigate the clinical efficacy of cerdulatinib, a dual effect Syk / JAK inhibitor, in the treatment of recurrent refractory (R / R) PTCL and CTCL.
research method
Patients with R / R PTCL or CTCL were treated with cerdulatinib 30mg Po bid until disease progression, intolerability or feasible stem cell transplantation. The main end point was objective response rate. The PTCL group was compared with Lugano standard, and the CTCL group was compared with global evaluation standard.
Research results
In this study, 61 cases of PTCL and 37 cases of CTCL were included. In the PTCL group, 60 patients could evaluate the efficacy (or rate 35%), mainly in AITL / TFH subtype (or rate 55%, CR rate 41%). The orr rate of CTCL group was 35%, and mycosis fungoides was the highest (ORR rate 45%, CR rate 9%), while that of Sezary syndrome was 17%, no CR.
research conclusion
Cerdulatinib has good tolerance and effectiveness to R / R PTCL and CTCL.
Abstract 199: safety and antitumor activity of cd5-car-t cells in relapsed / refractory T cell malignancies
Research background
CD5 is a pan-t cell surface marker in about 85% of T cell malignant tumors. In this study, a second generation cd5-car-t with CD28 costimulatory signal domain was developed to investigate the safety and feasibility of cd5-car T cells as a bridge of allo HSCT in the treatment of R / R T cell malignant tumors (NCT 03081910).
research method
Cd5-car-t cells were obtained from the patient's PBMC, which were transduced by retroviral vector and cryopreserved. The patients were treated with a single dose of cd5-car-t cells after the pretreatment. The clinical reactions, adverse events and the in vivo expansion and persistence of car-t cells were observed.
Research results
Nine patients with CD5 + R / R T-ALL (n = 4) and T-NHL (n = 5) were included. Three patients received 1 × 107 car-t cells / m2, and six patients received 5 × 107 car-t cells / m2. After 4-8 weeks of infusion, 4 patients were evaluated, and the objective curative effect was obtained (1 case of low dose level, 3 cases of high dose level), 3 cases of Cr (1 case of AITL, 1 case of PTCL, 1 case of T-ALL). Two of them were unwilling or unable to perform HSCT, and recurred 6 weeks and 7 months after infusion. The remaining patients are currently undergoing HSCT. The main adverse events were CRS 1-2 and neurotoxicity.
research conclusion
Cd5-car-t cells are safe in the treatment of relapsed and refractory T-cell lymphoma. They can be used as induction therapy to remove malignant T cells in R / R CD 5 + T-ALL and T-NHL patients, and as a bridging scheme to enable patients to obtain HSCT opportunities.
Abstract 463: a randomized, controlled, open, multicenter clinical trial to compare the efficacy and safety of the modified ddgp protocol and the smile protocol for extranodal NK / T cells in the late stage of primary diagnosis (stage III / IV)
Research background
Advanced extranodal NK / T-cell lymphoma (enktcl) has a low response to conventional chop like regimens, with a 5-year OS rate of only 30%. Previous studies have shown that smile and asparaginase based combination chemotherapy are effective for enktcl patients. The purpose of this study was to evaluate and compare the efficacy and safety of modified ddgp and smile in patients with advanced enktcl (NCT 01501149).
research method
Patients were randomly divided into two groups: ddgp group (cisplatin 20 mg / m2, D1-D4; dexamethasone 15 mg / m2, D1-5; gemcitabine 800 mg / m2, D1, D8; Pei asparaginase 2500 IU / m2, D1) and smile group (methotrexate 2 g / m2, D1; dexamethasone 40 mg / m2, d2-4; ifosfamide 1500 mg / m2, d2-4; L-asparaginase 6000 U / m2, d3-9; etoposide 100 mg / m2 D 2-4), 21 days as a cycle, up to six courses of treatment, unless the disease progress, intolerable, patients refused to stop. The efficacy was evaluated every two cycles. The primary endpoint was PFS, and the secondary endpoint included Orr and OS.
Research results
87 enktcl patients were randomly divided into ddgp group (n = 40) and smile group (n = 40). The 3-year PFS rate, 5-year OS rate and orr rate of ddgp group were higher than those of smile group (56.6% vs 41.8%, 74.3% vs 51.7%, 90.0% vs 60.0%). There was no significant difference in CR rate between the two groups. The incidence of non hematologic toxicity and grade 3 / 4 hematologic toxicity in smile group was higher than that in ddgp group. The TRM in ddgp group was 17.5% and about 10% respectively.
research conclusion
The efficacy and safety of modified ddgp is better than that of smile in the newly diagnosed patients with enktcl.
Comments on Professor Fan Lei
T/NK cell lymphoma is a group of highly heterogeneous diseases, which are derived from mature T cells and NK cells, accounting for 5% to 15% of all NHL. The incidence rate in China is higher than that in western countries. At present, the first-line treatment of PTCL is still the option of chop, but in addition to low-risk ALK + ALCL, the 5-year OS rate is only 30-40%, and the clinical prognosis is poor. Once the disease relapses and is difficult to treat, the clinical progress is more rapid. Compared with B-cell lymphoma, t / NK cell lymphoma, especially in relapsed and refractory patients, has made relatively slow progress in new drugs. At present, in addition to the survival benefits of BV in CD30 + patients, other progress is limited. Abstract 466 reported that cerdulatinib, as a dual effect Syk / JAK inhibitor, had an orr rate of 35% in 60 patients with PTCL, mainly in AITL / TFH subtype (ORR rate of 55%, CR rate of 41%), in 37 patients with CTCL, Orr rate of 35%, mycosis fungoides was the highest (ORR rate of 45%, CR rate of 9%). This study suggests that cerdulatinib has good tolerance and efficacy to R / R PTCL and CTCL, but there seems to be difference in efficacy between different subtypes. In addition, car-t cell therapy, as an important progress in the field of B-cell lymphoma / leukemia in recent years, has significantly improved the clinical efficacy of B-cell tumor patients, but the development of T-cell lymphoma is slow due to the limitations of the target. We are pleased to see that abstract 199 of this meeting reported the efficacy evaluation of the second generation cd5-car-t cells with CD28 costimulatory signal domain on R / R T cell malignant tumors. In all 9 cases, 4 cases were observed objective curative effect, 3 cases were Cr, 7 cases were entered into follow-up HSCT, which confirmed the safety of cd5-car-t treatment, and won the opportunity for follow-up stem cell transplantation.
NK/T cell lymphoma (ENKTCL) is highly aggressive in clinic. The incidence rate in China is significantly higher than that in western countries. Early treatment with aspartate based chemotherapy combined with chemotherapy can cure most patients, but the prognosis of patients with advanced stage is poor. Smile, as the first-line treatment plan designed by Japan and South Korea, although the efficacy is acceptable, the side effects are significant. Abstract 463 of this meeting reported a clinical trial aimed to compare the effectiveness and safety of modified ddgp scheme and smile scheme for enktcl in the late stage of initial diagnosis. The results showed that ddgp group was superior to smile scheme in both efficacy and safety, providing a new treatment option for clinical application.
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Typesetting editor: amiee
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