Research progress in lymphoma

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On June 17-20, 2015, the 13th International Lymphoma Conference was successfully held in Switzerland. 3700 representatives from 90 countries participated in the event. At the meeting, the research on lymphoma was brilliant, not only the summary of multi-center randomized controlled trials, but also the initial effect analysis of new drug treatment, and the report of the research results of pathogenesis, etc., which is undoubtedly the diagnosis and diagnosis of lymphoma. The treatment further pointed out the direction and presented a gluttonous feast to the clinician.

1. Follicular lymphoma: the new treatment endpoint
progression-free survival (PFS) is the primary endpoint of first-line treatment of follicular lymphoma, but because of the longer follow-up period (expected ≥ 7 years), there are certain limitations . The FLASH team conducted a prospective meta-analysis (abstract number: 122), and the results showed that a complete response at 30 months (CR30) may be the primary endpoint of the first-line treatment study of follicular lymphoma. The study included 13 clinical trials and a total of 3837 patients were available for evaluation. The results showed that the linear correlation coefficient of CR30 and PFS at the trial level was 0.88, and the Copula model correlation coefficient was 0.86; the risk ratio at the patient level was 0.703. In the subgroup with invasive disease (stage IV or high FLIPI score), the correlation between the two is more obvious.

2. Hodgkin’s lymphoma: medium-term PET-CT guided treatment
The international multi-center prospective RATHL study (abstract number: 008) included 1214 patients with newly-treated adult Hodgkin lymphoma, all of which were stage ⅡB-Ⅳ, or ⅡA combined with large masses, or ≥3 affected sites. All patients were given 2 cycles of ABVD chemotherapy followed by PET-CT (PET2). PET2 negative patients were randomly given 4 cycles of ABVD regimen or AVD regimen chemotherapy, and then entered the follow-up period. PET2-positive patients were given 4-cycle BEACOPP-14 regimen or 3-cycle enhanced BEACOPP regimen chemotherapy, and then performed PET-CT examination again (PET3); PET3-negative patients continued to receive 2-cycle BEACOPP-14 regimen or 1-cycle enhanced BEACOPP regimen chemotherapy; Patients with PET3 positive were given radiotherapy or salvage chemotherapy. Regardless of whether there is a large mass at baseline or whether there are residual lesions after treatment, if the mid-term PET-CT test is negative, no radiotherapy will be given. Results PET2 was negative in 84% of patients, with a median follow-up of 32 months, 3-year PFS was 83%, and overall survival rate (OS) was 95%. The 3-year PFS of the ABVD regimen group and the AVD regimen group were similar (85.45% and 84.48%, respectively), and the 3-year OS was not statistically different (97.0% and 97.5%, respectively), but the lung toxicity of the ABVD regimen was significantly higher than that of AVD The protocol suggests that it is safe and effective to remove bleomycin in the ABVD protocol.

3. Primary lymphoma of central nervous system: Titipe and rituximab increase the efficacy
IELSG32 is an international multi-center prospective phase II trial (abstract number: 009), including 227 patients with newly-treated primary central nervous system lymphoma, with a median age of 58 years (18-70 years). Randomly divided into three groups: Group A was given 4 cycles of MTX 3.5g / m2 (d1), Ara-C 2g / m2 (d2-3); Group B was given rituximab 375mg / m2 (d -5, d0); Group C was given Titipipe 30 mg / m2 (d4) on the basis of Group B; those who were effective were randomly divided into whole brain radiotherapy group and carmustine combined with Titipi pretreatment combined with autologous Stem cell transplantation group. Results The total effective rates of the three groups were 53%, 74%, and 87%, CR rates were 23%, 31%, and 49%, and the 5-year failure-free survival rates were 34%, 43%, and 54%, respectively. The OS was 27%, 50%, and 66%, respectively, suggesting that adding rituximab and titipe to the treatment plan can significantly improve the efficacy and improve the long-term prognosis.

4. Antigen chimeric receptor T cell (CAR-T) treatment: initial results
CTL019 cells are CAR-T cells targeting CD19 and show good anti-tumor effects in patients with relapsed and refractory leukemia. A phase II clinical trial (abstract number: 139) verified the efficacy of CTL019 cells in the treatment of CD19-positive non-Hodgkin’s lymphoma. The study included 29 patients with relapsed refractory lymphoma, including 19 cases of diffuse large B-cell lymphoma, 8 cases of follicular lymphoma, and 2 cases of mantle cell lymphoma. The median age is 56 years old. 1-4 days after chemotherapy, 5 × 108 CTL019 cells were given intravenously. Results The total effective rate was 68%. Among them, the CR rate of diffuse large B-cell lymphoma was 42%, and the partial remission (PR) rate was 8%; the CR rate of follicular lymphoma was 57% and the PR rate was 43%. 15 patients developed cytokine release syndrome. With a median follow-up of 6 months, PFS was 59%. Tip CTL019 cell therapy is safe and effective.

5. Double-strike against diffuse large B-cell lymphoma: Selinexor is effective in vitro and in vivo
Selinexor is an oral selective inhibitor of nuclear export, inhibits XPO1, promotes nuclear retention and activation of more than 10 tumor suppressor proteins, and reduces c-myc and BCL2 / 6 protein levels through nuclear retention of Eif4e. In an in vitro test (abstract number: 146), Selinexor has a good inhibitory effect on double-strike diffuse large B-cell lymphoma cell line DoHH2, and it also has a good inhibitory effect on MYC or BCL2 mutant cell lines. In the Phase I clinical trial, 6 patients received Selinexor treatment, and 3 patients achieved remission, of which 1 patient was confirmed by CR on PET-CT and 2 patients received PR.

In addition, the prognostic index of chronic lymphocytic leukemia and mantle cell lymphoma was also discussed and analyzed at this conference, and more clinical pathological indicators were introduced to judge the long-term prognosis; and the World Health Organization Lymphoma Classification 2016 The updated content of the edition was also presented in advance at the conference. In short, the convening of this grand event has pointed out a new direction for the diagnosis and treatment of lymphoma, and will certainly further optimize the individualized treatment based on evidence-based medicine.

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