Treatment Efficacy and Safety of Bortezomib Combined with Dexamethasone and Lenalidomide Chemotherapy Regimen for Multiple Myeloma

Objective:To analyze the effect of bortezomib combined with dexamethasone and lenalidomide in the treatment of multiple myeloma.Methods:60 cases of multiple myeloma patients admitted to our hospital from January 2022 to December 2023 were selected randomly,with 30 cases in each group.Bortezomib combined with dexamethasone was administered in the control group,and bortezomib combined with dexamethasone and lenalidomide was given to the observation group,and the treatment effect was analyzed.Results:After treatment,CD^(3+)and CD^(4+)of the observation group were higher than that of the control group,CD^(8+)was lower than that of the control group,and the total treatment efficiency was higher,which was statistically significant(P<0.05),and there was no difference in the total incidence of adverse reactions between the two groups(P>0.05).Conclusion:Bortezomib combined with dexamethasone and lenalidomide is effective in the treatment of multiple myeloma as it regulates the immune function and is safe,thus it can be promoted in clinical practice.

Long-term durable response to lenalidomide in a patient with hepatic epithelioid hemangioendothelioma

Epithelioid hemangioendothelioma(EH)is a rare tumor arising from the vascular endothelial cells of soft tissue or visceral organs.The most common visceral site is the liver,where it is often involved in a multifocal man-ner known as hepatic EH(HEH).Surgical resection with curative intent represents the gold standard therapy.When surgery is not feasible,or in cases of metastatic disease,no standard medical treatment is currently indicated.In small series,drugs with anti-angiogenic activity(such as bevacizumab,sorafenib,thalidomide,and lenalidomide)have been proposed with promising results.We describe a 73-year-old man with multifocal non-resectable HEH treated with lenalidomide.Disease status was evaluated by abdominal ultrasound and magnetic resonance every four months.The patient was treated for a total of 39 mo with prolonged disease stabilization and,at the time of writing,is still under treatment with a good tolerance profile.During a short period of treatment discontinuation,the disease showed slight progression that immediately resolved after the reintroduction of lenalidomide.Lenalidomide may represent a valid treatment option for HEH due to its anti-angiogenic and antineoplastic activities.This preliminary result merits further study in a large series.

Subcutaneous panniculitis-like T-cell lymphoma invading central nervous system in long-term clinical remission with lenalidomide:A case report

BACKGROUND Subcutaneous panniculitis-like T-cell lymphoma(SPTCL)involvement in the central nervous system(CNS)is particularly rare.SPTCL with CNS involvement has an exceedingly poor prognosis,and no optimum therapeutic method has been discovered.To the best of our knowledge,this is the first reported case of SPTCL invading the CNS achieving long-term remission with lenalidomide maintenance therapy.CASE SUMMARY A 63-year-old man diagnosed with SPTCL was admitted to the hospital with severe headache for 15 d after four cycles of chemotherapy.Subsequent to the treatment,the patient developed CNS involvement.Craniotomy biopsy was pathologically diagnosed as CNS T-cell lymphoma,and two courses of chemotherapy were performed postoperatively.Due to the intolerance of the side effects of chemotherapeutic drugs,the patient received lenalidomide instead.The magnetic resonance imaging of the head at the 8 mo follow-up indicated no signs of recurrence,and the vital signs were stable.CONCLUSION Lenalidomide deserves further investigation as a targeted drug for SPTCL cases involving the CNS.

Role of lenalidomide in the treatment of peripheral T-cell non-Hodgkin lymphomas

T-cell lymphomas(TCLs)represent a group of lymphoid neoplasms characterized by an aggressive clinical course,even after an anthracycline-containing regimen.Novel agents for patients with relapsed/refractory TCL are urgently needed.Lenalidomide is an oral drug with immunomodulatory,antiangiogenic and direct antineoplastic effects.These peculiar mechanisms of action make TCL an attractive target for lenalidomide.We have identified five clinical trials in which lenalidomide monotherapy was investigated to treat TCL,including cutaneous TCL(CTCL)and adult T-cell lymphoma/leukemia(ATLL).In the ATLL-002 study,the overall response rate(ORR)was 42%and median progression-free survival(PFS)and overall survival were 3.8 mo and 20.3 mo,respectively.In a phase II trial for CTCL,ORR was 28%and median PFS and overall survival were 8 mo and 43 mo,respectively.For nodal peripheral TCL,ORR was between 10%and 43%in three clinical trials,with a median PFS of about 4 mo,even if some patients had a durable response.Overall toxicity is manageable and grade 3-4 events are mainly hematological and reversible.Combination strategies did not improve PFS.In conclusion,lenalidomide could represent a suitable treatment option for relapsed/refractory TCL,especially for neoplasms with a T-follicular helper origin,such as angioimmunoblastic TCL.

Dexamethasone plus lenalidomide in treatment of multiple myeloma

Combination of lenalidomide with dexamethasone （LD） is of high effectiveness for treatment of multiple myeloma （MM）, resulting in an improved overall survival, response rate, and time to progression in relapsed or refractory MM. Adverse events, especially venous thromboembolism, were generally well tolerated. In addition, lenalidomide plus dexamethasone is a potential therapy in maintenance of myeloma.

Successful Treatment of Low-Dose Lenalidomide Maintenance Therapy Followed by Second Autologous Peripheral Blood Stem Cell Transplantation in Heavily Treated Multiple Myeloma

Recently, the prognosis of multiple myeloma has been improved by using high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT), bortezomib, and immunomodulatory drugs including thalidomide and lenalidomide. On the other hand, treatment strategy remains difficult for refractory and relapse cases. Here, we report the successful treatment of low-dose lenalidomide maintenance therapy followed by salvage ASCT in a heavily treated patient with multiple myeloma. This 58-year-old woman with IgG-λ multiple myeloma had a 5th recurrence in June, 2011. It was 7 years post-diagnosis, and she had received conventional therapies such as VAD, MP therapy. Furthermore, the patient had already been treated with ASCT, bortezomib, and thalidomide therapy. At the 5th recurrence, she had extramedullary plasmacytoma in the left orbit. She initially received bortezomib and dexamethasone therapy as induction therapy. After peripheral blood stem cell collection, radiation therapy was performed. The patient then received a second ASCT. Three months later, the response was very good partial response. Finally, the patient was treated with 5 mg/day lenalidomide orally as a maintenance therapy, and she achieved stringent complete response after 2 months according to International Myeloma Working Group response criteria. Low-dose lenalidomide maintenance therapy might be also useful for ASCT as salvage therapy, although further studies are warranted.

Lenalidomide and Arsenic Trioxide Have Independent Non-Interfering Effects When Used in Combination on Myeloma Cell Lines in <i>Vitro</i>

Multiple myeloma (MM) is a plasma cell neoplasm characterized for its fast evolution and for being practically incurable, presenting a strong need for the development of therapies to target it. Among those under study are lenalidomide and arsenic trioxide (ATO) which show individual clinical promise, although never tested together. However, the combination of ATO with thalidomide, another immunomodulatory drug and lenalidomide’s structural albeit less potent analog, have been tried clinically with some success. Therefore, we investigated the effect the combination of lenalidomide and ATO have on the MM-derived U266 and RPMI 8226 cell lines. We observed that both compounds have separate, non-interfering, anti-myeloma mechanisms with ATO demonstrating strong cytotoxic effects while lenalidomide’s role remains cytostatic and immunomodulatory. However, ATO decreases cdc25c, which helps sensitize cells to lenalidomide effects enhancing the efficacy of their interaction. Mechanistically the combination of these two agents decreased the expression of MDM2, without affecting p53 activation or its expression. Therefore, this short study provides the foundation to continue mechanistic studies of the combination of lenalidomide and ATO as a foundation for future clinical application.

New antimyeloma drugs in spinal cord infiltration for multiple myeloma. Determination of lenalidomide in cerebrospinal fluid with ultrasensitive high-performance liquid chromatography

A 64-year-old woman with IgA kappa multiple myeloma was treated with thalidomide-dexa- methasone. Due to progression of the disease, bortezomib, doxorubicin and dexamethasone were administered, followed by autologous stem cell transplantation. Although near-complete remission was achieved, 5 months later, neuro- logical symptoms appeared and the patient was diagnosed with multiple myeloma with cells in- filtrating the spinal cord. Bis-chloronitrosourea, bortezomib and lenalidomide were then admin- istered and although the patient remained neu- rologically asymptomatic, she died 3 months later becausee of disease progression. Lena- lidomide entered into the cerebrospinal fluid (confirmed by ultrasensitive high-performance liquid chromatography), although did not im- prove the poor prognosis of multiple myeloma involving the central nervous system.

Follow-Up Study of a Multiple Myeloma Patient Successfully Treated with Clarithromycin (CAM), Low-Dose Lenalidomide and Low-Dose Dexamethasone: Significance and Possible Mechanism of Action of CAM as an Add-On Therapy

Background: Recently, high efficacy of the chemotherapeutic regimen combining clarithromycin (CAM) with lenalidomide (Len) and dexamethasone (Dex) (BiRD) in treating multiple myeloma (MM) patients has been reported. However, the exact mechanism of added CAM has not been fully elucidated. This case report will provide helpful information for understanding the significance and the mechanism of action of CAM as an add-on therapy. Patient: A 78-year-old female patient with IgA-λ type MM was treated with low-dose Len coupled with low-dose Dex (low Rd), and excellent response was achieved for long term, but she later became refractory to this treatment. Then, CAM was added to low Rd (low Rd-CAM, i.e., modified BiRD therapy). This add-on-therapy was found to be effective, but later suspended because of pneumonitis. Then, low-dose Len coupled with CAM (low R-CAM) treatment was applied;but effect of this Dex-free treatment was insufficient. Thus, low Rd-CAM was reapplied and satisfactory reduction of IgA was achieved. This fact suggests that low Rd-CAM is the favorable combination, Dex is requisite and CAM might have enhanced the effect of Dex. In this case, various serum cytokines were examined during the course of illness. Only interleukin-6 showed apparent increase, and tumor necrosis factor-α, transforming growth factor-β, soluble IL-2 receptors and C-reactive protein showed the slight increase during low Rd-CAM treatment. The results seem somewhat conflicting, but it seems that intricate cytokine response due to immune activation might have occurred during low Rd-CAM treatment.

Rapid Disappearance of Testicular Plasmacytoma after Treatment with Lenalidomide plus Dexamethasone

We describe a rare case of testicular plasmacytoma first manifesting as a relapse. The patient was initially diagnosed with IgG-λ-type multiple myeloma and treated with melphalan and prednisolone plus bortezomib, achieving a complete remission. Four months later, his left scrotum began to swell and pathological investigation of a needle biopsy specimen revealed proliferation of plasma cells expressing IgG-λ, confirming myeloma recurrence. However, bone marrow aspiration samples showed no significant increase in myeloma cells and there was no skewed deviation of the K/λ ratio on flow-cytometric analysis. The extramedullary tumors disappeared completely soon after treatment with lenalidomide plus dexamethasone, and the patient was judged to be in very good partial remission based on negative M-protein results by serum immunoelectrophoresis. This is the first report, to our knowledge, describing complete disappearance of a testicular plasmacytoma after treatment with lenalidomide as the key-drug.

Study on Efficacy and Safety of Bortezomib in Combination with Lenalidomide and Dexamethasone in the Treatment of Newly Diagnosed Multiple Myeloma

Objective:To investigate the clinical effects of combining bortezomib with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma.Methods:This study was conducted in Shaanxi Provincial People’s Hospital from January 2020 to January 2022.25 patients were selected for the study and divided into two groups:12 patients in one group,the control group,were treated with bortezomib and thalidomide in combination with dexamethasone,and 13 patients in the other group were treated with bortezomib and dexamethasone.The other group of 13 patients,given bortezomib combined with lenalidomide and dexamethasone,was named as the experimental group,and the treatment effects of the two groups were compared and analyzed.Results:Comparing the treatment efficiency of the two groups,the incidence of patients in the experimental group was 92.31%,which was significantly higher than that of the control group(33.33%),with a significant difference,indicated as P<0.05.At the same time,the incidence of adverse reactions in the experimental group was lower,the clinical index scores were closer to normal values,and the level of inflammatory response was lower,with significant differences in all data in the control group(P<0.05),and the experimental group had better treatment results.Conclusion:Bortezomib combined with lenalidomide and dexamethasone is clinically effective in the treatment of newly diagnosed patients with multiple myeloma,and is of positive significance in promoting recovery.

Clinical Efficacy of Lenalidomide Combined with Cyclophosphamide and Dexamethasone in the Treatment of Multiple Myeloma

Objective:Multiple myeloma has a great impact on patients;the use of implant denture restorative treatment is ideal,and it is vital to carry out scientific treatment methods.Methods:The research subjects were inclusive of 60 patients with mxiltiple myeloma,who were randomly selected from January 2019 to December 2019.The patients were divided into a study group and a control group,with 30 patients in each group.The patients in the control group were treated with conventional treatment,while the patients in the study group were treated with lenalidomide combined with cyclophosphamide and dexamethasone.The effectiveness of treatment,adverse effects,and clinical indices of the two groups were compared.Results:Comparing different treatment methods,the differences in the indices between the two groups were statistically significant(p<0.05).Conclusion:The use of lenalidomide combined with cyclophosphamide and dexamethasone in the treatment of patients with multiple myeloma increases the effectiveness of treatment and improves patientsJ clinical indices;thus,it is worthy of promotion.

Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome with dilated cardiomyopathy: A case report

BACKGROUND Polyneuropathy,organomegaly,endocrinopathy,M-protein,skin changes(POEMS)syndrome is a rare paraneoplastic syndrome that encompass multiple systems.The most common clinical symptoms of POEMS syndrome are pro-gressive sensorimotor polyneuropathy,organ enlargement,endocrine disorders,darkening skin,a monoclonal plasma cell proliferative disorder,and lymph node hyperplasia.The organomegaly consists of hepatosplenomegaly and/or lym-phadenopathy;cases of cardiomyopathy are rare.Diagnoses are often delayed because of the atypical nature of the syndrome,exposing patients to possibly severe disability.Therefore,identifying atypical symptoms can improve the prognosis and quality of life among POEMS syndrome patients.lenalidomide and dexamethasone.CONCLUSION When patients with cardiomyopathy have systemic manifestations such as numb limbs and darkening skin,the POEMS syndrome is the most possible diagnosis.

Efficacy and Safety of Lenalidomide in the Treatment of Multiple Myeloma： A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background：Lenalidomide has emerged as an important treatment for patients with multiple myeloma （MM）.However,its role in the management of MM is still controversial and requires further clarification.The aim of this study was to evaluate efficacy and safety of lenalidomide for MM using a meta-analysis.Methods：We searched the electronic databases including：PubMed,EMBASE and the Cochrane Center Register of Controlled Trials.Seven randomized clinical trials were identified,which included a total of 2357 patients with MM who received lenalidomide-containing,noncontaining lenalidomide regimens or placebo as induction therapy or maintenance therapy.The outcomes included overall response （OR） rate,complete response （CR） rate,3-year progression-free survival （PFS） rate,3-year overall survival （OS） rate,and different types of treatment-related adverse events.We calculated the risk ratios （RRs） as well as their 95％ confidence intervals of these outcomes and pooled the results using RevMan 5.2 software.Results：For patients with previously untreated MM,OR rate and CR rate was significantly higher in lenalidomide-containing group than the control group.For relapsed or refractory MM patients,lenalidomide-containing regimens significantly improved the OR rate,CR rate,3-year PFS rate and 3-year OS rate.With regard to MM patients after autologous stem cell transplantation,lenalidomide maintenance therapy significantly improved 3-year PFS rate but did not result in improved 3-year OS rate.In terms oftoxicities,lenalidomide therapy has a higher rate of Grade 3-4 grade cytopenias,infection,deep-vein thrombosis,and diarrhea.Furthermore,the incidence of second primary malignancies was significantly higher in the lenalidomide group.Conclusions：The lenalidomide-containing regimens as induction therapy clearly increased response rates and improved intervals of survival with acceptable toxicity rates for patients with MM.However,when physicians choose to use the lenalidomide as maintenance therapy,whether the benefits outweigh the risks should be taken into account.

Salvage therapy with lenalidomide containing regimen for relapsed/refractory Castleman disease： a report of three cases

Castleman disease （CD） is an uncommon non-clonal lymphoproliferative disorder with unknown etiology. No standard therapy is recommended for relapsed/refractory CD patients, thus requiring development of novel experimental approaches. Our cohort of three adult patients with multicentric CD （MCD） were treated with refractory to traditional chemotherapy lenalidomide-containing regimens （10-25 mg lenalidomide perorally administered on days 1-21 in 28-day cycle） as second- to fourth-line treatment. Partial remission was achieved in first plasma-cell CD patient, who relapsed seven months after autologous hematopoietic stem cell transplantation and then failed to respond to four cycles of chemotherapy. Partial remission was obtained in second patient with CD and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Third case showed complete remission with complete disappearance of pleural effusion and ascites and normalization of platelet count. To conclude, encouraging clinical responses were achieved in cohort of three patients with lenalidomide-based regimen, though long-term efficacy remains to be observed. We propose further investigation of therapeutic potential of this drug in treating MCD.

Helical tomotherapy and systemic targeted therapies in solitary plasmacytoma: Pilot study

AIM: To assess the feasibility of the combination of helical tomotherapy(HT) and a concurrent systemic targeted therapy in patients with solitary plasmacytoma (SP) with the aim to decrease toxicity while improving therapeutic efficacy. METHODS: Six patients with biologically, histologically, and radiologically confirmed SP were treated using HT and a systemic targeted treatment concomitantly. Total dose was 40 Gy/20 fractions. Four patients received 4 cycles of concurrent lenalidomide-dexamethasone combination and two patients were treated with concomitant bortezomib-dexamethasone. All toxicities were described using the Common Terminology Criteria for Adverse Effects v3.0.RESULTS: Five patients had a bone tumor and one patient had an isolated pancreatic mass. Five patients presented with pain, one had neurologic symptoms related to medullary compression, which was treated by an emergency surgery. Median age was 59.5 years (range, 50-74 years). All patients had initial positron emission tomography-computed tomographys, three patients had total body bone magnetic resonance imaging examination, and three patients had computed tomodensitometry scans. The toxicity profile was excellent with no higher than grade 1 toxicity. Four of the six patients experienced a partial radiological response, four had complete response on positions emission tomography and 5/6 patients experienced a complete relief of their symptoms 4 mo after treatment. At a median follow-up of 18 mo, 5/6 patients were controlled clinically, radiologically, and biologically. CONCLUSION: Using HT, we could deliver a highly conformal irradiation concurrently with a molecularly targeted therapy. This association yielded in a high response rate and a low toxicity. A prospective study with longer follow-up will help determining the true benefit of such strategy.

Del(5q) and inv(3) in myelodysplastic syndrome: A rare case report

BACKGROUND Del(5q)is the most common molecular event in myelodysplastic syndrome(MDS),accounting for 10%-15%of cases.Inv(3)is an adverse cytogenetic abnormality observed in less than 1%of MDS patients.Few studies have reported the coexistence of del(5q)and inv(3)in MDS.Therefore,the pathological mechanism,treatment strategy and prognosis of this subtype need to be elucidated.CASE SUMMARY A 66-year-old woman was admitted to the hospital due to chest tightness and shortness of breath.Combining clinical assessments with laboratory examinations,the patient was diagnosed with MDS containing both del(5q)and inv(3).Considering the deletion of chromosome 5q,we first treated the patient with lenalidomide.When drug resistance arose,we tried azacitidine,and the patient had a short remission.Finally,the patient refused treatment with haematopoietic stem cell transplantation and died of severe infection four months later.CONCLUSION MDS patients with del(5)and inv(3)have a poor prognosis.Azacitidine may achieve short-term remission for such patients.

Adult Langerhans cell histiocytosis and immunomodulatory drugs:Review and analysis of thirty-four case reports

Langerhans cell histiocytosis(LCH)is a rare neoplastic disease in dendritic cells.LCH is classified as either a single-system(SS)or multisystem(MS)disease.There is not a standard first-line treatment for LCH in adults.We analyzed the efficacy and safety of immunomodulatory drugs(IMiDs)by searching PubMed/MEDLINE for case reports previously published.The clinical response(nonactive disease or active disease that regressed)was 94%in SS and 53%in MS.IMiDs should only be considered for adults with cutaneous SS involvement;in MS,they should be used only for patients not eligible for more aggressive treatments.