Study of PD-1 Monoclonal Antibody in Combination With Chemotherapy in Patients With RR NHL
Study of PD-1 Monoclonal Antibody in Combination With Chemotherapy in Patients With RR NHL
Lymphoma is one of the fastest growing malignancies in the world, with an annual incidence
 rate of about 4%. Non-Hodgkin's lymphoma (NHL) is highly heterogeneous and can be broadly
 divided into two major categories, B-cell lymphoma and T/NK cell lymphoma. It is composed of
 diseases of different pathological types and malignant degrees, and the prognosis is not the
 same.The anti-PD-1 antibody may benefit patients with relapsed or refractory Hodgkin's
 lymphoma. At the same time, in non-Hodgkin's lymphoma, PD1 antibodies also show promising
 therapeutic prospects. We propose this research program, based on the previous research at
 home and abroad, to further clarify the role of PD-1 monoclonal antibody combined with
 chemotherapy in the treatment of relapsed and refractory NHL patients, evaluate its clinical
 efficacy and safety, and explore The best treatment strategy for patients with relapsed and
 refractory NHL in China.
Lymphoma is one of the fastest growing malignancies in the world, with an annual incidence
 rate of about 4%. In recent years, the incidence of malignant lymphoma in China has increased
 rapidly. It has risen to the ninth place among the top ten high-incidence tumors in men, and
 the female has risen to the eleventh place. In 2011, the incidence of lymphoma in the country
 has reached 6.43/100,000.

 According to the characteristics of clinicopathology, lymphoma is divided into two
 categories: Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). HL is a single disease,
 relatively rare, but the prognosis is good, and patients with limited period have no progress
 for 5 years. The survival rate was 85-95%, and the 5-year progression-free survival rate of
 advanced patients was 30-85%. NHL is highly heterogeneous and can be broadly divided into two
 major categories, B-cell lymphoma and T/NK cell lymphoma. It is composed of diseases of
 different pathological types and malignant degrees, and the prognosis is not the same.

 In recent years, immunological checkpoint inhibitors have been the focus of research in the
 field of malignant tumor treatment. In clinical trials, PD-1/PD-L1 was found to be abnormally
 expressed in various lymphomas, including T-cell lymphoma, mediastinal large B-cell lymphoma,
 classical Hodgkin's lymphoma (CHL), and large variability. Cell lymphoma. Previous studies
 have evaluated the effects of antibody-based drugs against PD-1 (such as navobizumab and
 pabuleizumab) in patients with relapsed or refractory classic Hodgkin's lymphoma, and A
 higher response rate is shown and the security feature is acceptable. The domestic ORIENT-1
 study showed that ididilimumab was highly active in patients with relapsed or refractory
 classic Hodgkin's lymphoma in China, and 80% (74/92) patients had an objective response. No
 patients died during the study. Of the 96 patients treated, 89 (93%) had treatment-related
 adverse events, including 17 (18%) patients with grade 3 or 4 treatment-related adverse
 events, and 11 patients (11%) experienced severe Adverse events, but no unexpected or
 off-target safety signals were found. Therefore, PD1 antibodies may benefit patients with
 relapsed or refractory Hodgkin's lymphoma.

 At the same time, in non-Hodgkin's lymphoma, PD1 antibodies also show promising therapeutic
 prospects. Clinical studies at home and abroad have shown that PD-1 inhibitors are effective
 in relapsed or refractory extranodal NKT lymphoma. The results of the Idiliumab ORIENT-4 test
 showed that 1 year OS 82.1%, ORR 67.9%, DCR 85.7%, and PD-1 inhibitor combined with citabin
 to treat relapsed or refractory extranodal NKT is underway; PD-1 inhibitor monotherapy for
 relapsed or refractory PTCL is generally effective (ORR 33%, 4 of them CR); PD-1 inhibitor
 monotherapy is effective in treating relapsed or refractory mycosis/Sezary syndrome (ORR)
 37.5%) has been recommended by the NCCN guidelines; trials in combination with IFN γ-1b are
 underway. PD-1 inhibitor monotherapy for relapsed or refractory PMBCL or PCNSL is effective,
 and PD-1 inhibitors have been recommended by the NCCN guidelines for the former treatment.

 Therefore, we propose this research program, based on the previous research at home and
 abroad, to further clarify the role of PD-1 monoclonal antibody combined with chemotherapy in
 the treatment of relapsed and refractory NHL patients, evaluate its clinical efficacy and
 safety, and explore The best treatment strategy for patients with relapsed and refractory NHL
 in China.
Inclusion Criteria:

 1. Non-Hodgkin's lymphoma (NHL) confirmed by histopathology, preferably in the detection
 of tumor tissue PD-L1 expression.

 2. A recurrent or refractory disease defined as: 1) recurrence of disease after complete
 remission (CR); or 2) partial remission (PR), disease stabilization (SD), or disease
 Progress (PD) when the treatment is completed prior to enrollment in the study.

 3. Age≥18 years old, both men and women.

 4. The ECOG score is 0-2.

 5. There is at least one evaluable lesion (maximum diameter>15mm or shortest
 diameter>10mm). Preferably, PET-CT shows high metabolism of FDG.

 6. Have received appropriate first-line and more-line treatment of the corresponding NHL.

 7. Liver and kidney function: blood bilirubin≤35μmol/L, AST or ALT is less than 2 times
 the upper limit of normal value, serum creatinine≤150μmol/L.

 8. The thyroid function is normal.

 9. Women of childbearing age are required to undergo a pregnancy test before receiving
 treatment and must agree to take effective contraception during treatment.

 10. Subjects must sign an informed consent form.

 Exclusion Criteria:

 1. Age<18 years old；

 2. Received ASCT within 90 days prior to the first use of the study drug;

 3. Severe allergies, or patients known to be allergic or intolerant of the drug
 components of the chemotherapy regimen;

 4. Active, unrecognized or suspected autoimmune disease, or a history of autoimmune
 disease within 2 years;

 5. Previously exposed to any antibody against PD-1, PD-L1 or cytotoxic T
 lymphocyte-associated antigen 4

 6. Exposure to any study drug within 4 weeks prior to the first use of the study drug

 7. Expose to the last radiotherapy or anti-tumor therapy (chemotherapy, targeted therapy,
 immunotherapy or arterial embolization) within 3 weeks prior to the first use of the
 study drug.

 8. Have a history of oncology and have received any treatment for this tumor in the past
 3 years;

 9. Patients during pregnancy and lactation;

 10. Accompanied by severe heart disease, including acute myocardial infarction within 6
 months, or in accordance with New York Heart Association cardiac function III or IV;

 11. A serological test for HIV or active hepatitis C virus is known to be positive;

 12. Hepatitis B virus carriers or hepatitis B virus DNA positive untreated patients are
 known;

 13. TB patients active period

 14. Other circumstances that the investigator believes are not suitable for inclusion.