Efficacy and safety of daratumumab-based combined regimens for relapsed/refractory multiple myeloma / 白血病·淋巴瘤

Objective:To explore the clinical efficacy and safety of daratumumab-based combined regimens for relapsed/refractory multiple myeloma (RRMM).Methods:A retrospective case series study was conducted. The clinical data of 38 patients with RRMM in Jining NO.1 People's Hospital from Janunary 2020 to December 2022 were retrospectively analyzed. All patients were treated with daratumumab-based combined regimens. The Dd regimen (12 cases) was treated with daratumumab and dexamethasone, the DPD regimen (20 cases) was treated with pomalodomide based on the Dd regimen, the DVD regimen (6 cases) was treated with bortezomib based on the Dd regimen. The therapeutic efficacy and adverse reactions of all groups were analyzed. Kaplan-Meier method was used for survival analysis.Results:The median follow-up time was 9.5 months (1.0 months, 32.5 months) and the median treatmemt time was 6.2 months (3.2 months, 25.6 months). Among 38 patients, 7 cases (18.7%) achieved complete remission, 9 cases (23.6%) achieved very good partial remission, 10 cases (26.3%) achieved partial remission, 4 cases (10.5%) achieved minimal remission, 5 cases (13.1%) achieved stable disease, 3 cases (7.9%) had the progression of the disease. The overall response rate (ORR) was 78.9% (30/38). The ORR was 66.7%(8/12), 83.3%(5/6), 85.0%(17/20), respectively in the Dd group, DVD group and DPD group. There was no statistically significant difference in the ORR between the DVD group and DPD group ( χ2 = 0.01, P>0.05); there was no statistically significant difference in the ORR between the DVD group and Dd group ( χ2 = 0.55, P>0.05); there was no statistically significant difference in the ORR between the DPD group and Dd group ( χ2 = 1.47, P>0.05). The median progression-free survival (PFS) time was 12.5 months (95% CI: 8.5-24.2 months),the median overall survival (OS) time was not reached, and the 1-year OS rate was 89.4%. Among 38 patients, the main adverse reactions during treatment were infusion-related adverse reactions in 5 cases, grade 3 neutropenia in 7 cases, grade 3 thrombocytopenia in 9 cases, severe anemia in 12 cases; no one had drug discontinuation or drug reduction due to the intolerance of adverse reactions. Conclusions:Daratumumab-based combined regimens in the treatment of RRMM show a favorable efficacy and safety.

Pomalidomide improves airway inflammation and mucus hypersecretion in COPD rats by inhibiting TNF-α/NF-κB signaling pathway / 解放军医学杂志

Objective To investigate the effect and mechanism of pomalidomide(POM)on airway inflammation and mucus hypersecretion in rats with chronic obstructive pulmonary disease(COPD).Methods Thirty-six SD rats were randomly divided into control group,model group and POM group,with 12 in each group,half male and half female.The COPD model was established by smoke exposure combined with Klebsiella pneumoniae infection in model group and POM group.The rats in POM group were treated with POM(0.5 mg/kg,once a day for 1 week).The lung function,lung tissue pathology,the proportion of inflammatory cells in bronchoalveolar lavage fluid(BALF)and the levels of serum inflammatory factors tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6 and IL-13 were observed and detected in each group.AB-PAS staining and immunohistochemistry were used to analyze the proliferation of goblet cells and the secretion of mucin(MUC)5AC and MUC5B in airway epithelium of rats.The expression levels of TNF-α receptor 1(TNFR1),IκB kinase(IKK),phosphorylated IKK(p-IKK)and P65 protein in lung tissue were detected by Western blotting.Results Compared with control group,model group showed significant decreased of tidal volume(TV),minute ventilation(MV),forced expiratory vital capacity(FVC),0.1s forced expiratory volume(FEV0.1)and 0.3 s forced expiratory volume(FEV0.3)(P<0.05),increased of the mean linear intercept(MLI)of the alveoli(P<0.01),decreased of the mean alveolar number(MAN)(P<0.01),increased of the proportion of neutrophils and lymphocytes in BALF sediment(P<0.05),and decreased of the proportion of macrophages in BALF sediment(P<0.01);increased of the levels of serum inflammatory factors TNF-α,IL-1β,IL-13 and IL-6(P<0.05),the proportion of goblet cells in airway epithelium(P<0.01),the secretion of MUC5AC and MUC5B in lung tissue(P<0.01),the content of TNFR1 and the ratio of p-IKK/IKK(P<0.01),the content of P65 in nucleus(P<0.01);and decreased of the content of P65 in cytoplasm(P<0.05).Compared with model group,after one week of POM treatment,POM group showed significant improved of the TV,MV,FVC,FEV0.1,FEV0.3,MLI and MAN of rats(P<0.05);decreased of the proportion of neutrophils and lymphocytes in BALF(P<0.05);increased of the proportion of macrophages(P<0.01);decreased of the levels of serum TNF-α,IL-1β,IL-6 and IL-13(P<0.05),the proportion of goblet cells in airway(P<0.01),the secretion of MUC5AC and MUC5B(P<0.01),and the expression of TNFR1,P-IKK and P65(nucleus)(P<0.05);and increased of the level of P65(cytoplasm)(P<0.01).Conclusions POM can improve airway inflammation and mucus hypersecretion in COPD rats,which may be achieved by inhibiting TNF-α/NF-κB signaling pathway.

Progress of pomalidomide for relapsed/refractory multiple myeloma / 白血病·淋巴瘤

Multiple myeloma (MM) is a plasma cell malignant proliferative hematological tumor. At present, a variety of drugs including immunomodulators (IMiD) and proteasome inhibitors (PI) have been used to treat MM, and the progression-free survival time of patients has been significantly prolonged. Because the immune dysfunction of MM patients has not been fundamentally corrected, most of them will eventually relapse and develop drug resistance. Pomalidomide, a third-generation IMiD, has achieved a high response rate in clinical trials of patients with relapsed/refractory multiple myeloma (RRMM) who did not respond to lenalidomide or bortezomib. This article reviews the mechanism of pomalidomide and the efficacy and safety of relevant clinical trials, so as to investigate the treatment measures for RRMM.

Efficacy and safety of pomalidomide combined with cyclophosphamide and dexamethasone in treatment of relapsed/refractory multiple myeloma / 肿瘤研究与临床

Objective:To investigate the therapeutic effect and safety of pomadomide combined with cyclophosphamide and dexamethasone (PCD) in the treatment of relapsed/refractory multiple myeloma (MM).Methods:The clinical data of 20 relapsed/refractory MM patients receiving PCD regimen in the Second People's Hospital of Lianyungang Affiliated to Bengbu Medical College from March 2021 to June 2022 were retrospectively analyzed; and 29 relapsed/refractory MM patients receiving other regimens including DECP (dexamethasone+etoposide+cyclophosphamide+cisplatin, 13 cases) and VCD (bortezomib+ cyclophosphamide+ dexamethasone, 16 cases) during the same period were treated as the control group. The efficacy and adverse effects of both groups were compared after 4 cycles of treatment.Results:After 4 cycles of treatment, the overall response rate (ORR) and the clinical benefit rate (CBR) of 20 cases in PCD group was 70.0% (14/20) and 85.0% (17/20), respectively; among 20 cases, there were 5 cases of complete response (CR), 4 cases of very good partial remission (VGPR), 5 cases of partial remission (PR), 3 cases of minimal remission (MR), 2 cases of stable disease (SD), 1 case of the progression of the disease (PD). ORR and CBR of 29 cases in the control group was 41.4% (12/29) and 65.5% (19/29), respectively; among 29 cases, there were 2 cases of CR, 3 cases of VGPR, 7 cases of PR, 7 cases of MR, 5 cases of SD, 5 cases of PD. There was a statistically significant difference in ORR of both group ( χ2 = 3.89, P = 0.048), while the difference in CBR of both group was not statistically significant ( χ2 = 2.30, P = 0.129). There were 2 patients with renal impairment achieving CR in PCD group and 1 patient with renal impairment achieving CR in the control group ( P = 0.152); 1 genetically high-risk patient achieved CR in PCD group and none of patients in the control group achieved CR, and the difference was statistically significant ( P>0.05). The common hematological adverse effects of two groups were anemia, neutropenia, thrombocytopenia; the common non-hematological adverse effects were malaise, infection and fatigue, and the differences were statistically significant (all P>0.05). The incidence of grade 3-4 infection was 25.0% (5/20) in PCD group and the disease was under the control after anti-infective therapy, and the incidence of grade 3-4 infection was 24.1% (7/29) in the control group; and the difference was not statistically significant ( P > 0.05). Conclusions:PCD regimen has good clinical efficacy and safety in treatment of relapsed/refractory MM.

Bendamustine combined with pomalidomide and dexamethasone in relapsed multiple myeloma with extramedullary disease: a multicenter study / 中华血液学杂志

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.

Clinical Anslysis of TAFRO Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics, diagnosis, and treatment of one patient with TAFRO syndrome, and to strengthen the understanding of this rare type.@*METHODS@#The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in Gansu Provincial People's Hospital were retrospectively analyzed.@*RESULTS@#Combined with laboratory tests, bone marrow examination, imaging, pathology, etc, the patient was diagnosed with TAFRO syndrome. After three cycles of treatment with pomalidomide (2-3 mg/d, d1-21), cyclophosphamide (300 mg/m2, 0.54 g once a week) and dexamethasone (20 mg/d, two days a week), platelet count, serum creatinine and procalcitonin returned to normal, the systemic edema disappeared, and the patient's condition was alleviated. The therapeutic effect was good.@*CONCLUSION@#TAFRO syndrome is rare, involves multiple systems, progresses rapidly, and has a worse prognosis. The choice of the "Pomalidomide+cyclophosphamide+dexamethasone" regimen is help to improve the survival prognosis of patient with TAFRO syndrome.

Efficacy observation of pomalidomide-based regimen in treatment of relapsed/refractory multiple myeloma / 白血病·淋巴瘤

Objective:To investigate the early efficacy and safety of pomalidomide-based regimen in relapsed/refractory multiple myeloma (MM) in the real world.Methods:The clinical data of 15 patients with relapsed/refractory MM treated with pomalidomide-based regimen who were admitted to Gansu Provincial Hospital from January 2021 to July 2021 were retrospectively analyzed, and the early efficacy and safety were also evaluated.Results:There were 8 males and 7 females, and the median age of onset of 15 patients was 60 years (43-83 years); the median time for the diagnosis of relapse and refractory was 15 months (4-84 months). All 15 patients previously received bortezomib-based treatment regimens, 9 patients previously received lenalidomide treatment, and 7 cases received autologous hematopoietic stem cell transplantation. All patients received pomalidomide-based regimen combined with two-drug or three-drug regimen (pomalidomide combined with bortezomib,daratumumab,bendamustine, dexamethasone, cyclophosphamide or lenalidomide). The median treatment cycle was 2 cycles (2-4 cycles). After 2 cycles of treatment, the therapeutic efficacy was evaluated; the overall response rate was 73% (11/15), including 3 cases of complete remission, 3 cases of very good partial remission, and 5 cases of partial remission. Hematological toxicity occurred in 9 patients, of which 5 cases had grade 3-4 hematological toxicity, 4 cases had grade 1-2 hematological toxicity, and other adverse reactions were mild and tolerable.Conclusion:Pomalidomide-based regimen is effective and safe for relapsed/refractory MM patients.

Progress of pomalidomide for treatment of relapsed/refractory multiple myeloma / 肿瘤研究与临床

Multiple myeloma (MM), ranking the second most common malignancy in the blood system, is a heterogeneous disease characterized by clonal proliferation of plasma cells producing immunoglobulin. Due to the wide use of new drugs, including proteinase inhibitor (PI), immune modulators (IMiD) and monoclonal antibodies, great progress has been made in the treatment of MM, but almost all patients eventually develop drug resistance. Pomalidomide is the third generation of IMiD and a very well tolerated regimen for relapsed/refractory MM. This paper summarizes the combined therapy based on pomalidomide to provide the theoretical basis for a better clinical application of pomalidomide.

<b>2．Points for Evaluation of the Revised Risk Minimization Plans on Thalidomide and its </b><b>Derivatives </b> / 薬剤疫学

<p>Thalidomide and the derivatives, lenalidomide and pomalidomide, are the most potent teratogenic medicines. Thalidomide Education and Risk Management System （TERMS^®）and RevMate^® for lenalidomide and pomalidomide have been operated with a goal of no exposed embryo to the drugs. The TERMS^®and the RevMate^®, a centralized management system, were revised in 2016 according to a request by a patient group. After the revision, the patient self-check sheet on adherence to conception prevention is primarily confirmed by his/her doctor, and the content of the completed sheet is sent to the management center in the pharmaceutical company after dispensing of the drug. The points for evaluation of the revised system will be as follows. (1) Has an appropriate procedure in accordance with the revised system been established in respective hospitals? (2) The rate of non-compliance with the procedure by the doctors or pharmacists, (3) Effect on awareness and behavior of the patients. Questionnaire studies of the patients, doctors, and pharmacists have been performed by the third-party committees.</p><p></p>

2．Points for Evaluation of the Revised Risk Minimization Plans on Thalidomide and its Derivatives / 薬剤疫学

Thalidomide and the derivatives, lenalidomide and pomalidomide, are the most potent teratogenic medicines. Thalidomide Education and Risk Management System （TERMS®）and RevMate® for lenalidomide and pomalidomide have been operated with a goal of no exposed embryo to the drugs. The TERMS®and the RevMate®, a centralized management system, were revised in 2016 according to a request by a patient group. After the revision, the patient self-check sheet on adherence to conception prevention is primarily confirmed by his/her doctor, and the content of the completed sheet is sent to the management center in the pharmaceutical company after dispensing of the drug. The points for evaluation of the revised system will be as follows. (1) Has an appropriate procedure in accordance with the revised system been established in respective hospitals? (2) The rate of non-compliance with the procedure by the doctors or pharmacists, (3) Effect on awareness and behavior of the patients. Questionnaire studies of the patients, doctors, and pharmacists have been performed by the third-party committees.

Research progress of pomalidomide in the treatment of relapsed refractory multiple myeloma / 白血病·淋巴瘤

Pomalidomide,which represents a new generation of immunomodulatory drugs (IMiD),has brought a major shift in therapeutic paradigm in treating relapsed and refractory multiple myeloma (RRMM).Considering its encouraging effectiveness,the U.S.Food and Drug Administration (FDA) approved its usage to treat patients who fail to respond to at least two prior therapies,including lenalidomide and bortezomib,and whose disease progressed within 60 days of the last treatment.This review summarizes the mechanisms of action and clinical activity of pomalidomide in treating RRMM.