Efficacy of lenalidomide in treatment of multiple myeloma and its effect on levels of regulatory T cells and natural killer cells of patients / 白血病·淋巴瘤

Objective:To investigate the clinical efficacy of lenalidomide combined with bortezomib and dexamethasone (RVd) regimen in treatment of newly diagnosed multiple myeloma (NDMM) patients and its effect on the levels of regulatory T cells (Treg cells) and natural killer (NK) cells.Methods:Thirty-eight NDMM patients who were admitted to the Second Affiliated Hospital of Bengbu Medical College from September 2019 to May 2022 were selected for a prospective study, and were divided into control group (18 cases) and observation group (20 cases) according to random number table method. The control group was treated with bortezomib+epirubicin+dexamethasone (VAd) regimen, and the observation group was treated with RVd regimen. The efficacy and safety were compared between the two groups. The levels of Treg cells (CD4 + CD25 + FOXP3 +) and NK cells (CD3 - CD56 + CD16 +) before and after treatment in the two groups were detected by flow cytometry, and the results were compared. Results:After 4 courses of treatment, the objective response rate (ORR) of the observation group was 95.0% (19/20), which was higher than that of the control group [77.8% (14/18)], and the difference was statistically significant ( P = 0.016). Before treatment, there was no statistical difference in the levels of Treg cells and NK cells between the two groups ( P values were 0.381 and 0.650). After treatment, the level of Treg cells in the control group increased from (1.5±0.5)% before treatment to (4.7±1.3)% ( P = 0.008), while the level of Treg cells in the observation group increased from (1.4±0.5)% before treatment to (6.8±1.5)% ( P = 0.001), and the level in the observation group was higher than that in the control group ( P = 0.027); the level of NK cells in the control group increased from (16±6)% before treatment to (20±5)% ( P = 0.004), while the level of NK cells in the observation group increased from (16±6)% before treatment to (24±6)% ( P = 0.006), and the level in the observation group was higher than that in the control group ( P = 0.032). The incidence rates of thrombocytopenia and neutropenia in the observation group were higher than those in the control group, and the differences were statistically significant ( P values were 0.012 and 0.027), which was reversible after active treatment. There was no statistical difference in the incidence rates of other adverse reactions (all P>0.05). Conclusions:RVd regimen for NDMM is clinically effective, safe and reliable, and the patients' levels of Treg cells and NK cells elevate after treatment.

A single-center retrospective analysis of 100 consecutive cases treated with lenalidomide/bortezomib/dexamethasone in newly diagnosed multiple myeloma / 中华内科杂志

Objective:To investigate the efficacy and safety of lenalidomide combined with bortezomib and dexamethasone (RVD) in patients with newly diagnosed multiple myeloma (NDMM).Methods:A total of 100 consecutive NDMM patients treated with RVD from August 2016 to September 2020 at Peking University People′s Hospital were retrospectively analyzed, including response, drug toxicity, follow-up and survival, and subgroup analysis.Results:The median follow-up time was 19.5 (2.0-57.0) months. For patients undergoing autologous stem cell transplantation (ASCT) after RVD regimen, the objective response rate (ORR)/complete response+stringent complete response (CR+sCR)/≥very good partial response (VGPR) rates were 100%, 73.3% (33/45), 95.6% (43/45) respectively. For 54 patients not receiving transplantation, the ORR/CR+sCR/≥VGPR rates were 79.6% (43/54), 18.5% (10/54), 51.9% (28/54) respectively. As to the survival analysis, 2-year progression free survival (PFS) rates were 84.5% and 70.9% in transplant and non-transplant patients respectively ( P=0.102). Two-year overall survival (OS) rates were 100% and 80.8% in transplant and non-transplant patients respectively ( P=0.003). The common hematologic adverse events (AEs) were thrombocytopenia (33%) and neutropenia (25%). Abnormal liver function (43%) and peripheral neuropathy (24%) were recognized more as non-hematologic AEs. Conclusion:RVD as front-line regimen has high efficient response rate and acceptable safety in Chinese NDMM patients.

Research Progress of Clonal Hematopoiesis of Indeterminate Potential in Multiple Myeloma --Review / 中国实验血液学杂志

With the progress of medical technology, cloning hematopoietic was found to be widely exist in normal people. Because of its clinical significance and prognosis is unclear, it is named clonal hematopoiesis of indeterminate potential(CHIP), which has been detected in blood diseases such as myelodysplastic syndrome and lymphoma, and proven to be related to poor prognosis. Recently, CHIP has been also detected in patients with multiple myeloma (MM). In this article, the definition and influencing factors of CHIP, clinical significance, prognosis and treatment in MM were reviewed.

Cost-utility analysis of dexamethasone combined with bortezomib and lenalidomide in the treatment of newly diagnosed multiple myeloma / 中国药房

OBJECTIVE To eval uate the cost-util ity of regimen containing bortezomib in the treatment of newly diagnosed multiple myeloma in China. METHODS From the perspective of China ’s health system ，Markov model was constructed based on SWOG S 0777 clinical trial. The simulation time limit was 10 years，and the cycle was set with reference to the treatment cycle. Taking quality adjusted life years （QALYs）as the utility index ，the utility and cost were discounted at a discount rate of 5％；the willingness to pay （WTP）threshold was set to be 3 times of China ’s per capita gross domestic product （GDP）in 2021（242 928 yuan/QALY）. The incremental cost-utility ratio （ICER）of dexamethasone combined with bortezomib and lenalidomide （VRD） versus dexamethasone combined with lenalidomide （RD）were compared with cost-utility analysis. The sensitivity analysis was performed for the uncertainty of the model. RESULTS Results of baseline analysis showed that VRD regimen could obtain 0.65 more QALYs than RD scheme ，but its treatment cost was 135 782.77 yuan more than RD regimen ，ICER was 206 623.35 yuan/ QALY，which was lower than the WTP threshold set in this study ，VRD regimen was cost-effective. Single factor sensitivity analysis showed that the health utility value in progressive free survival had the greatest impact on the results ，the decrease of utility value would make the ICER higher than the WTP threshold ，and VRD regimen would no longer have advantages. Under the WTP threshold of 3 times of China ’s per capita GDP in 2021，the probability of VRD regimen being cost-effective was 86.5％； with the increase of WTP threshold ，the possibility of VRD regimen becoming more cost-effective than RD regimen would increase. CONCLUSIONS Under the WTP threshold of 3 times of China ’s per capita GDP in 2021，compared with RD regimen，VRD regimen is cost-effective in the treatment of newly diagnosed multiple myelo ma in China.

Efficacy observation of lenalidomide in treatment of relapsed/refractory diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To explore the clinical efficacy of lenalidomide combined with second-line immunochemotherapy as a salvage regimen in the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 37 relapsed/refractory DLBCL patients receiving lenalidomide combined with second-line immunochemotherapy as a salvage regimen who had recurrence after autologous hematopoietic stem cell transplantation or who were not eligible for transplantation or had no intention to transplant between January 2016 and December 2020 in the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed. Among 37 patients, 6 cases with primary central nervous system (CNS) lymphoma and 3 cases with secondary CNS lymphoma. The short-term efficacy after treatment was evaluated. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS), and log-rank test was used for subgroup comparison.Results:The median follow-up time of 37 patients was 20.4 months (2.7-37.0 months). At the end of treatment, the overall response rate (ORR) of all patients was 64.9% (24/37), the complete response (CR) rate was 45.9% (17/37), and the median duration of response (DOR) of 24 patients who responded to treatment was 17.7 months (3.6-33.6 months). The median PFS time of all patients was 11.2 months, and the 1-year PFS rate was 48.6% (95% CI 32.5%-64.7%). The median OS time of all patients was not reached, and the 1-year OS was 67.6% (95% CI 52.5%-82.7%). Among 24 responding patients, 17 cases who received lenalidomide maintenance therapy after remission tended to have a better response compared with 7 cases who did not receive lenalidomide maintenance therapy after remission, although there was no significant difference in OS and PFS between both groups (both P > 0.05). Additionally, neutropenia was the most common adverse reaction with an incidence of 81.1% (30/37). Conclusions:Lenalidomide combined with the second-line immunochemotherapy may be an effective salvage therapy for patients with relapsed/refractory DLBCL, especially for patients with CNS involvement. The patients achieving remission after salvage therapy continue to receive lenalidomide maintenance therapy and could have a better prognosis.

Cyclophosphamide-glucocorticoids versus lenalidomide-dexamethasone as treatment for multiple myeloma at first relapse after autologous stem cell transplantation - a retrospective analysis

ABSTRACT There have been significant improvements in therapeutic options for relapsed multiple myeloma (MM) over the past two decades, with many novel agents including proteasome inhibitors, immunomodulatory agents, and more recently monoclonal antibodies demonstrating efficacy in this setting. However, there is a paucity of real-world data comparing outcomes seen in patients treated with novel agents as opposed to older agents. We report a historical single center cohort of patients diagnosed with myeloma between the years 1991-2012 in order to explore possible differences in outcomes. A total of 139 patients who underwent stem cell transplantation were included in our study. In our study, 88 patients were treated with cyclophosphamide and steroids alone at relapse whereas 51 patients were treated with Len-Dex. In the multivariate analysis, TTNT was shorter for patients who received Cyclo compared to Len-Dex (HR = 1.74; 95% CI, 1.01-2.99; p = 0.04); however, we could not detect an overall survival benefit (HR = 1.20; 95% CI 0.63-2.29; p = 0.57). Adverse event rates were similar in the two groups. In this retrospective single center analysis, Len-Dex was associated with longer TTNT compared with Cyclo at first relapse following autoSCT in MM; however its effect on overall survival in this setting was less clear.

Progress of enhancing the function of chimeric antigen receptor T-cells in replased/refractory B-cell malignancies / 白血病·淋巴瘤

When chimeric antigen receptor T cells (CAR-T) failed to treat relapsed and refractory B-cell malignancies, some researchers try to improve the efficacy by enhancing the function of CAR-T. It is a new hotspot of drug development and clinical research, and significant achievements have been made in this area recently. Multi-targeted CAR-T, lenalidomide, decitabine, programmed death 1 inhibitor and ibrutinib can all enhance the function of CAR-T. This article reviews the recent progress of enhancing the function of CAR-T in relapsed and refractory B-cell malignancies.

Transitory response of a myelodysplastic syndrome with deletion of chromosome 5q to thalidomide. Report of one case

ABSTRACT Myelodysplastic syndrome with deletion of chromosome 5q (5q-syndrome) has a favorable prognosis and a low risk of transformation to acute myeloid leukemia, when treated with lenalidomide. Azacitidine leads to complete remission even as second-line therapy and in patients with clonal evolution. We report a 70 years old female without previous exposure to myelotoxic drugs, presenting with three weeks with fatigue and dyspnea. She had anemia with normal white blood cell and platelet count. Bone marrow biopsy showed 50% cellularity and the karyotype analysis revealed a (5) (q33q34) deletion in 22% of the metaphases. A diagnosis of 5q-syndrome with low risk calculated using the Revised International Prognostic Scoring System (IPSS-R), was made. Since lenalidomide was not affordable, thalidomide 100 mg/day was initiated, achieving transfusion independence for three years. Afterwards, she developed pancytopenia and a bone marrow biopsy showed erythroid and megakaryocyte dysplasia with a complex karyotype, which worsened prognosis (IPSS-R of five points). Therefore, azacitidine (by donation) was administered. She achieved complete remission with a normal karyotype and completed 12 cycles of treatment. Thereafter, she relapsed and received only supportive care for a year. She suffered an ischemic stroke and died two weeks later.

El síndrome mielodisplásico con deleción del cromosoma 5q (síndrome 5q) tiene un pronóstico favorable y riesgo bajo de transformación a leucemia aguda en pacientes que son tratados con lenalidomida (tratamiento estándar). El uso Azactidina tiene respuestas completas incluso como segunda línea de tratamiento en pacientes con evolución clonal. Presentamos una mujer de 71 años, sin exposición a mielotóxicos que debutó con un síndrome anémico. Se realizó biopsia de medula ósea que mostró celularidad del 50% y en el análisis citogenético se detectó una deleción del cromosoma 5 en 22% de las metafases analizadas, lo que llevó al diagnóstico de Síndrome 5q- de riesgo bajo de acuerdo con el puntaje IPSS-R (Revised International Prognostic Scoring System). Ya que no se pudo costear lenalidomida, se trató con talidomida (100 mg/día). Permaneció tres años sin requerir soporte transfusional. Posteriormente, presentó pancitopenia y en el nuevo aspirado de médula ósea se observó displasia de la serie roja y megacariocitos, con cariotipo complejo y peor pronóstico (IPSS-R 5 puntos). Se trató con 12 ciclos de azacitidina con lo que logró respuesta completa. Recayó 12 meses después y continuó manejo de soporte por un año. Finalmente falleció debido a un accidente vascular cerebral.

Existe beneficio en la adición de Trasplante de Progenitores Hematopoyéticos a pacientes con Mieloma Múltiple que reciben Lenalidomida en la fase de mantenimiento? / Is there benefit in adding Hematopoietic Stem Cell Transplantation to patients with Multiple Myeloma who receive Lenalidomide in the maintenance phase?

Introducción: La controversia en el beneficio de la adición de trasplante de progenitores hematopoyéticos a pacientes que reciben Lenalidomida en la fase de mantenimiento de pacientes con MielomaMúltiple está en pleno debate en la comunidad científicapor lo que el objetivo del presenteestudio fue medir la supervivencia en un grupo de pacientesen estas condiciones. Métodos:El estudio tipo observacional analítico realizado con pacientes oncológicos ingresados en el Hospital SOLCA durante el periodo de enero del 2014-mayo del 2018.Con una muestra no probabilística se seleccionaron pacientescon Mieloma Múltiple,mayores de 18 años en cuyo tratamientose incluyeLenalidomida.Grupo 1(G1): pacientes con trasplante de médula ósea, Grupo 2: pacientes no candidatos a trasplante de médula ósea.Las variablesdemográficas, clínicasdescriptivas (ISS, ECOG), supervivenciacomo variable principaly efectos secundarios.se realizó el análisis de sobrevida de Kaplan-Meyer. Resultados:Se incluyeron 23 casos en G1y 26 casos en G2.La edad en G1 53 años (Rango38-70), en G2:65 años (Rango 46-85)P=0.13. En G1 fueron 12/23(52%) hombres,en G2 fueron 15/26 (57%) P=0.93. ISS grado II 11/23(48%) en G1 y 10/26(38%) en G2 P=0.51. ECOG 2 en G1:12/23(52%) y en G2 16/26 (32%) en G2 P=0.51. La supervivencia Libre de progresión en el Grupo 1-TPH a los 24 meses de seguimientofue del 98%,en el Grupo 2 no Candidato a TPH a los 24 meses de seguimiento fue de 82%, Logrank test P=0.023.X2=5.192.La supervivencia global en el Grupo 1-TPH a los 24 meses de seguimientofue del 100%,en el Grupo 2 no Candidato a TPH a los 24 meses de seguimiento fue de 90%, Logrank test P=0.17.X2=1.846. Conclusión:En el presente estudio se demostró que la sobrevida libre de progresión es mayor en el grupo de pacientes con Mieloma Múltiple sometidos a Trasplante de Progenitores Hematopoyéticos versus el grupo de pacientes con Mieloma Múltiple que no son candidatos a Trasplante. La sobrevida global es igual en ambos grupos.

Introduction: The controversy on the benefit of adding hematopoietic stem cell transplantation to patients receiving Lenalidomide in the maintenance phase of patients with Multiple Myeloma is in full debate in the scientific community, so the objective of this study was to measure survival in a group of patients in these conditions. Methods: This analytical observational study carried out with cancer patients admitted to the SOLCA Hospital during the period of January 2014-May 2018. With a non-probabilistic sample, patients with Multiple Myeloma, older than 18 years, were selected in whose treatment Lenalidomide is included. Group 1 (G1): patients with bone marrow transplantation, Group 2: patients not candidates for bone marrow transplantation. The demographic, descriptive clinical variables (ISS, ECOG), survival as the main variable and secondary effects. Kaplan-Meyer survival analysis was performed. Results:23 cases were included in G1 and 26 cases in G2. Age in G1 53 years (Range 38-70), in G2: 65 years (Range 46-85) P = 0.13. In G1 they were 12/23 (52%) men, in G2 they were 15/26 (57%) P = 0.93. ISS grade II 11/23 (48%) in G1 and 10/26 (38%) in G2 P = 0.51. ECOG 2 in G1: 12/23 (52%) and in G2 16/26 (32%) in G2 P = 0.51. Progression-free survival in Group 1-HSCT at 24 months of follow-up was 98%, in Group 2 not Candidate for HSCT at 24 months of follow-up it was 82%, LogRank test P = 0.023. X2 = 5.192. Overall survival in Group 1-HSCT at 24 months of follow-up was 100%, in Group 2 not Candidate for HSCT at 24 months of follow-up it was 90%, LogRank test P = 0.17. X2 = 1.846. Conclusion:In the present study, it was demonstrated that progression-free survival is higher in the group of patients with Multiple Myeloma who underwent Hematopoietic Stem Cell Transplantation versus the group of patients with Multiple Myeloma who are not candidates for Transplantation. Overall survival is the same in both groups.

T cell/histiocyte rich large B cell lymphoma of ascending colon: a rare entity

Colonic T cell/histiocyte rich large B cell lymphoma (THRLBCL) is a very unusual occurrence never described before. A 41-year anaemic male presented with loss of weight and appetite for 7 months and fever with Malena for 1 month. Abdominal examination revealed a 4×6 cm retroperitoneal lump in the right iliac fossa. Radiological investigations (USG and CECT whole abdomen) reported an asymmetrical ill-defined growth in ascending colon and caecum with loco-regional lymphadenopathy. Surgical exploration revealed an ascending colon mass with retroperitoneal lymphadenopathy. Right hemi-colectomy with end ileostomy was done and specimen was sent for histopathology which diagnosed it to be a case of THRLBCL of colon. Patient was followed up after 2 weeks and was planned for chemotherapy.

Autologous peripheral blood stem cell transplantation for POEMS syndrome / 中华内科杂志

Six patients with POEMS syndrome who received autologous peripheral blood stem cell transplantation (auto-PBSCT) were retrospectively analyzed.Conditioning regimen was high dose melphalan.Peripheral blood stem cells were collected after mobilization with cyclophosphamide (CTX) and growth factors.One patient presenting hydrothorax and ascites was treated with 3 cycles of lenalidomide and dexamethasone before mobilization.Auto-PBSCT was fairly tolerable.Hematopoietic reconstitution was successful in all patients without transplantation-related mortality.A decrease or normalization of serum vascular epithelial growth factor (VEGF) was observed in all patients at 3 months after transplantation.The neurological remission was seen in 5/6 patients.

Analysis of clinical characteristics, treatment response rate and survival of 77 myelodysplastic syndrome patients with del (5q) syndrome / 中华血液学杂志

Objective@#To observe the clinical characteristics, treatment responses and prognosis of patients with myelodysplastic syndrome (MDS) -del (5q) syndrome who met WHO (2016) diagnostic typing criteria.@*Methods@#A total of 77 patients with del (5q) syndrome, according to WHO (2016) classification, were retrospectively analyzed between January 2008 and April 2018 in the Blood Diseases Hospital, Chinese Academy of Medical Sciences. Clinical characteristics, lenalidomide (LEN) efficacy and survivals were compared between the patients with del (5q) alone and those with one additional cytogenetic abnormality (ACA) with the exception of monosomy 7 or del (7q) . Treatment response and overall survival (OS) were compared between patients who were treated with LEN and traditional non-LEN drugs.@*Results@#Of 77 patients, 64 were isolated del (5q) and 13 were del (5q) with ACA. There were significant differences of the median age and percentage of patients who had small megakaryocytes in bone marrow smear by immunohistochemistry (CD41) between the patients with isolated del (5q) and the patients with del (5q) + ACA[58 (29-64) years old vs 63 (31-82) years old, z=2.164, P=0.030; and 91.7%vs 60.0%, P=0.046, respectively]. The overall hematological response rate (78.9%vs 80.0%) , complete hematological remission (CR) rate (57.9% vs 60.0%) , cytogenetic response (CyR) rate[69.2% (9/13) vs 66.7% (4/6) ] and complete cytogenetic response (CCyR) rate [61.5% (8/13) vs 33.3% (2/6) ] of LEN were similar between the patients with isolated del (5q) (n=19) and with del (5q) + ACA (n=10) , as well as the median Overall survival (OS) between these two groups of patients (62 months vs 78 months, P=0.388) . The hematological response rate (79.3% vs 36.0%) , CR rate (58.6% vs 8.0%) , CyR rate [68.4% (13/19) vs 11.1% (1/9) ] and CCyR rate [52.6% (10/19) vs 0 (0/9) ] were higher among patients treated with LEN (n=29) than those treated with non-LEN therapy (n=25) . There was no statistically significant difference in OS between the patients with LEN or non-LEN therapy (78 months vs 62 months, P=0.297) .@*Conclusion@#Comparing del (5q) syndrome patients with isolated del (5q) or with del (5q) + ACA, two groups of patients had similar clinical characteristics, median OS and LEN efficacy. LEN showed better treatment response than traditional drugs in patients with del (5q) syndrome.

Effect of lenalidomide combined with interferon and interleukin-2 for treatment of refractory/relapsed or minimal residual disease-positive acute myelogenous leukemia / 白血病·淋巴瘤

Objective@#To analyze the efficacy and safety of lenalidomide combined with interferon (IFN) and interleukin-2 (IL-2) for treatment of refractory/relapsed or minimal residual disease (MRD)-positive acute myelogenous leukemia (AML).@*Methods@#Twelve patients with AML who were hospitalized in the Affiliated Cancer Hospital of Zhengzhou University from August 2013 to May 2019 were selected. These patients were previously treated with thalidomide combined with IFN and IL-2, and then treated with combined with IFN and IL-2. According to the Frence-American-British (FAB) classification system, there was 1 case of M0, 1 case of M1, 4 cases of M2a, 3 cases of M2b, 1 case of M4EO, and 2 cases of M5b. There were 2 cases with FLT3-ITD mutation-positive, 1 case with c-kit mutation-positive. There were 2 cases in the low-risk group, 7 cases in the intermediate-risk group, and 3 cases in the high-risk group. Three cases were refractory AML, 7 cases were relapsed AML (including 3 cases of recurrence once, 4 cases of recurrence twice; 5 cases of recent recurrence, 2 cases of long-term recurrence), 2 cases were MRD-positive. The efficacy and adverse reactions of 12 cases were evaluated.@*Results@#Twelve patients had received more than one cycle therapy of lenalidomide combined with IFN and IL-2, of which 4 patients achieved morphological complete remission (CR), 2 patients had CR with incomplete recovery of blood cells (CRi), 4 patients had no remission, 1 case had a decrease in MRD, and 1 case had an increase in MRD, and the total effective (CR+ CRi+ partial remission+ MRD decreased) was in 7 cases. There were no adverse reactions such as rash, constipine, bradycardia and peripheral neuritis; six patients had grade Ⅲ or higher experienced myelosuppression. No patients died of complications during the treatment, and the duration of remission of all patients was 2-20 months.@*Conclusion@#Lenalidomide combined with IFN and IL-2 for treatment of refractory/relapsed or MRD-positive AML is effective, and it can reduce the MRD value in MRD-positive patients, it could be a new treatment method for AML.

A combination of lenalidomide, bortezomib, and dexamethasone (RVD) provides deep-er responses in patients with newly diagnosed multiple myeloma / 中国肿瘤临床

Objective: This study investigated the efficacy and safety of a combination of lenalidomide, bortezomib, and dexametha-sone (RVD) in patients with newly diagnosed multiple myeloma (NDMM). Methods: The clinical features and responses of 48 patients with NDMM who were treated with RVD from January 2015 to May 2019 in Beijing Chaoyang Hospital were retrospectively analyzed. Results: The median age of the 48 patients was 59 years (range: 34-79). Among these, 44 patients were Durie-Salmon stageⅢ, 15 were ISS stageⅡ, 19 were ISS stageⅢ, and 12 had plasmacytoma; 32.5% of all patients were cytogenetic high-risk. All patients re-ceived a median of four cycles (range: 1-9) of the RVD regimen as induction treatment. The overall response rate was 97.9%, with 35.4% of patients achieving complete response (CR) or better. The rate of very good partial remission (VGPR) or better was increased from 64.1% (after two cycles) to 84.6% (after four cycles). The mean collection of CD34+cells was 4.2 (± 2.6)×106/kg. Negative minimal residual disease (MRD), as indicated by next-generation flow (NGF), was achieved in 20.6% of patients after induction. Two patients with positive MRD after induction became MRD negative after transplantation. Two patients developed grade 3 or 4 hematologic toxic-ity. No nonhematologic toxicity of grade 3 or 4 was observed. Conclusions: In patients with NDMM, RVD treatment resulted in signifi-cantly improved response rates and exhibited an acceptable risk-benefit profile, with no adverse impact on stem cell collection. RVD combined with transplantation significantly improved the negative rate of MRD, as indicated by NGF.

Efficacy observation of lenalidomide and rituximab in treatment of relapsed/refractory B-cell non-Hodgkin lymphoma / 白血病·淋巴瘤

Objective To evaluate the safety and efficacy of lenalidomide plus rituximab in treatment of the patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL). Methods The clinical data of the patients with relapsed/refractory B-NHL after the varieties of treatment methods in Peking Union Medical College Hospital between January 2015 and December 2017 were retrospectively analyzed. All the patients were treated with R2 regimen: oral lenalidomide (25 mg/d for day 1-day 21) and rituximab (375 mg/m2 of intravenous infusion on day 1, 28-day of each cycle); the efficacy was evaluated after three cycles. After this induction phase, the patients achieving complete response (CR), partial response (PR), or stable disease (SD) were given R2 regimen until the end of 8 cycles. The major end point was overall response rate (ORR) defined as CR + PR. Secondary end point included 1-year progression free survival (PFS), 1-year overall survival (OS) and grade 3-4 adverse events. T cell and B cell subsets of 7 patients at baseline were measured, and T cell and B cell subsets of 13 patients with good efficacy were dynamically observed. Results A total of 49 patients who received 1-4 chemotherapy regimens were included. The ORR after the R2 treatment for 3 courses was 65% (32/49). Thirty-six patients (9 cases of CR, 22 cases of PR, 5 cases of SD) were enrolled in R2 maintenance treatment. The median follow-up time was 13 months, 1-year PFS rate was 61% and 1-year OS rate was 84% . The most common adverse event was bone marrow suppression, including grade 3-4 neutropenia (27% ), grade 3-4 thrombocytopenia (6% ) and grade 4 anemia (4% ), most of which could be controlled by prolonging interval cycles or reduced lenalidomide dosage. The decreased number of CD19+B cell after treatment could be seen in 13 patients who obtained good efficacy under the dynamic observation. Conclusion Lenalidomide plus rituximab is well tolerated and highly active in the treatment of relapsed/refractory B-NHL.

Progress of lenalidomide in treatment of non-Hodgkin lymphoma / 白血病·淋巴瘤

In recent years,several large-scale clinical trials have confirmed that lenalidomide has a certain role in the treatment of non-Hodgkin lymphoma (NHL).Currently,the latest edition of the National Comprehensive Cancer Network (NCCN)guideline (2018.V3) recommend that lenalidomide could be used for multiple subtypes of NHL including diffuse large B-cell lymphoma,mantle cell lymphoma,follicular lymphoma,and marginal zone lymphoma.This article reviews the progress in the application of lenalidomide in NHL.

Clinical observation of lenalidomide in treatment of high-intermediate-risk B-cell non-Hodgkin lymphoma / 白血病·淋巴瘤

Objective To observe the clinical efficacy and safety of the lenalidomide-based therapy regimen in the treatment of high-intermediate-risk B-cell non-Hodgkin lymphoma (B-NHL). Methods A retrospective analysis of 23 high-intermediate-risk B-NHL patients who were admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2015 to February 2018 was conducted, of which 7 relapsed or refractory (R/R) patients received lenalidomide combined with rituximab (R2) and plus different salvage chemotherapy regimens (DHAP, GDP, ICE) of each 28-day cycle; 5 elderly patients were initially treated with R2 of each 28-day cycle; 11 patients were administered by maintenance monotherapy of lenalidomide of each 28-day cycle, or R2 therapy of 3-month cycle. The primary endpoint was overall response, and the secondary endpoints were progression-free survival (PFS) and safety. Results The median follow-up time was 4.5 months (1-20 months) in the R/R and elderly initial-treated patients. The median time to response in the R/R group was 3 months (2-7 months), of which 3 patients were complete remission (CR), overall response was 3 patients, and the median PFS was 7 months. The median time to response in the elderly initial treatment group was 4 months (2-5 months), 1 of 4 eligible patients was CR and 2 were partial remission (PR), overall response was 3 patients, and the median PFS time had not reached. The median follow-up time in the maintenance treatment group was 15 months (2-32 months), the median PFS time had not reached, and the 1-year PFS rate was 64％ (95％ CI 36％-92％). The most common grade 3-4 adverse events were leukopenia and thrombocytopenia, each accounting for 35％, and most patients were tolerable. Conclusion Lenalidomide as an immunomodulator is effective and safety for elderly initial treatment, R/R and maintenance treatment patients with high-intermediate-risk B-NHL, and it can prolong their survival.

The Usage of Acetylsalicylic Acid for Lenalidomide Medication in Patients with Multiple Myeloma / 医薬品情報学

Lenalidomide (LD) was reported to increase the risk of thromboembolism when it was used along with dexamethasone (DEX). Prophylactic administration of antithrombotic drugs against thromboembolism has been recommended for proper use of LD, but none of the recommendation is stated in the package insert. The purpose of this study was to elucidate the usage of acetylsalicylic acid (ASA) for lenalidomide medication in patients withmultiple myeloma. We used the MDV analyzer to investigate clinical data retrospectively. The investigation period was from October 1, 2016 to September 30, 2017. Subjects were outpatients aged 20 years or older who were recorded in clinical data as multiple myeloma. There were 7,590 outpatients with multiple myeloma. They were divided into 4 groups by the combined use situation of LD and DEX: LD/DEX non-use group (n＝5,462), DEX alone group (n＝632),LD alone group (n＝203), and LD/DEX together group (n＝1,293), respectively. The prevalence rate of thromboembolism was 7.3% in the DEX alone group and 16.9% in the LD/DEX together group (p＜0.0001). Among the LD/DEX together group, ASA was prescribed at 63.6% in the group without thromboembolism (n＝1,074). The prevalence rate of thromboembolism was higher in the LD/DEX combined group than in the DEX alone group. Considering these findings, risk management for thromboembolism caused by administration of antithrombotic drugs should be considered. It is necessary to create more evidence concerning the necessity of administration of antithrombotic drug in combination with LD/DEX medication.

Observation of lenalidomide combined with modified MP regimen in the treatment of elderly patients with multiple myeloma / 中国综合临床

Objective To investigate the clinical effect of lenalidomide combined with modified MP regimen in the treatment of multiple myeloma( MM) . Methods Eighty=four elderly multiple myeloma patients treated in Tangshan City Workers'Hospital from January 2013 December 2016 were enrolled in this study. The patients were randomly divided into treatment group ( 42 cases) and control group ( 42 cases) . The patients in the treatment group were given LMP regimen +α2b? interferon. The patients in the control group received the standard MPT regimen. The changes of the level of β2 microglobulin in the two groups before and after treatment were compared,and the total effective rate in the two groups was compared. Results No statistically significant difference was showed between the two groups in β2 microglobulin before treatment ( P>0. 05) . After treatment,β2 microglobulin concentration in the treatment group was (3. 11±0. 28) and was (4. 75±0. 36) in the control group,there was significant difference between two groups ( t=9. 094,P<0. 05); the total effective rate of the treatment group was 83. 33％,59. 52％ in the control group,there was significant difference between two groups ( t=5. 833,P=0. 016) . The incidence of adverse reactions in the treatment group was 9. 52％,the control group was 26. 19％,and the two groups were statistically significant ( t=3. 977,P=0. 046) . Conclusion The clinical effect of Lenalidomide combined with modified MP regimen in the treatment of MM is better than that of conventional treatment,the total effective rate is highwe,with less adverse reactions.

Update of diagnosis and treatment of plasma cell leukemia / 白血病·淋巴瘤

Plasma cell leukemia (PCL) is a rare and aggressive malignant plasma cell tumor that is clinically susceptible to extramedullary lesions. It is classified into two types: primary PCL (pPCL) and secondary PCL (sPCL), of which 60 % are pPCL. The treatment of new drugs such as bortezomib and lenalidomide is important for improving the overall survival and disease-free survival of PCL, especially after induction of bortezomib-based chemotherapy,combined with autologous hematopoietic stem cell transplantation (auto-HSCT) can improve the survival of patients. Whether to adopt the next step of allogeneic hematopoietic stem cell transplantation (allo-HSCT) still needs further investigation. For young and suitable patients, early new drug-based regimen chemotherapy combined with auto-HSCT can be used, and if a suitable donor is available, the further allo-HSCT consolidation therapy is feasible. For elderly patients (≥65 years old), a new drug-based regimen can be used to induce chemotherapy, and further followed consolidation therapy plus maintenance therapy. Whether to take auto-HSCT after early induction chemotherapy depends on the individualized factors of the patient. The next generation anti-plasma cells drugs, monoclonal antibodies and other immunotherapies or new drugs in clinical trials are also worth exploring.