Current treatment paradigm and survival outcomes among patients with newly diagnosed multiple myeloma in China:a retrospective multicenter study

Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).

Preliminary outcome of rituximab-containing salvage regimens on relapsed or refractory B-cell non-Hodgkin’s lymphoma: single institution experience

Objective： The prognosis of relapsed or refractory B-cell lymphoma is poor, with a short-term survival after conventional second-line chemotherapy, Rituximab, a chimeric anti-CD20 antigen, in combination with CHOP or CHOP-like chemotherapy may improve both disease free survival （DFS） and overall survival （OS） of naive patients, but its role in the second-line therapy for relapsed non-Hodgkin＇s Lymphoma （NHL） remains to be defined, This study aimed to evaluate the efficacy of rituximab-containing salvage regimens for relapsed or refractory NHL, and observe the toxicities. Methods： The clinical data of 54 patients, who were with relapsed or refractory NHL and treated in the Cancer Center of Sun Yat-sen University, were analyzed retrospectively, Of the 54 patients, 29 were man, 25 were women, with a median age of 52.5 years old （range 18 to 75）; 50 patients （92.6%） scored 0-1 for the ECOG performance status; for second-line international prognostic index （slPI）, 21 （38.9%） scored 0-1,30 （55.6%） scored 2 to 3, and 3 （5.6%） scored 4-5; 40 cases were diffuse large B-cell lymphoma （DLBCL）, accounting for 74.1% of all subtypes, Rituximab was administered intravenously at a dose of 375 mg/m^2 at the day before each chemotherapy cycle, The second or third-line salvage regimens included EPOCH, CHOP, DHAP, DICE, IVAC, IMVP-16 and FND, Results： Of the 54 patients, 49 received retuximab-containing salvage regimens, The objective response rate of the 45 evaluable cases was 68,8%, with a complete remission （CR） rate of 37.7%; 3 patients achieved CR after radiotherapy following rituximab-based regimens and 3 achieved CR after autologous hematopoietic stem cell transplantation, The most frequent adverse events were leucopenia, nausea and alopecia. The addition of rituximab to chemotherapy only elevated the occurrence of mild infusion-related reactions, such as chills, fever and pruritus. The median follow-up time was 18 months （range 2-86 months）; 5 patients were lost, 24 were dead （23 died of lymphoma, and 1 died of severe hepatitis）, the other patients remained alive. The median survival time was 32 months （range 2-86 months, 95% confidential interval 16-48 months）. The 1-, 2- and 3-year OS rates were 70.6%, 53,6% and 41,5%, respectively, The median TTP was 6 months （range 0-52 months）, The median PFS was 10 months （range 0-47 months, 95% CI 0-26 months）, The 1- and 2-year PFS were 49,3% and 41,3%. Conclusion： Rituximab-containing salvage regimens are effective and well tolerated therapy for patients with relapsed or refractory B-cell NHL, even those were extensively treated.

Targeting P21-activated kinase suppresses proliferation and enhances chemosensitivity in T-cell lymphoblastic lymphoma

T-cell lymphoblastic lymphoma(T-LBL)is a highly aggressive non-Hodgkin lymphoma with a poor prognosis.P21-activated kinase(PAK)is a component of the gene expression-based classifier that can predict the prognosis of T-LBL.However,the role of PAK in T-LBL progression and survival remains poorly understood.Herein,we found that the expression of PAK1 was significantly higher in T-LBL cell lines(Jurkat,SUP-T1,and CCRF-CEM)compared to the human T-lymphoid cell line.Moreover,PAK2 mRNA level of 32 relapsed T-LBL patients was significantly higher than that of 37 cases without relapse(P=.012).T-LBL patients with high PAK1 and PAK2 expression had significantly shorter median RFS than those with low PAK1 and PAK2 expression(PAK1,P=.028;PAK2,P=.027;PAK1/2,P=.032).PAK inhibitors,PF3758309(PF)and FRAX597,could suppress the proliferation of T-LBL cells by blocking the G1/S cell cycle phase transition.Besides,PF could enhance the chemosensitivity to doxorubicin in vitro and in vivo.Mechanistically,through western blotting and RNA sequencing,we identified that PF could inhibit the phosphorylation of PAK1/2 and downregulate the expression of cyclin D1,NF-κB and cell adhesion signaling pathways in T-LBL cell lines.These findings suggest that PAK might be associated with T-LBL recurrence and further found that PAK inhibitors could suppress proliferation and enhance chemosensitivity of T-LBL cells treated with doxorubicin.Collectively,our present study underscores the potential therapeutic effect of inhibiting PAK in T-LBL therapy.