Original Versus Generic Lenalidomide in Patients with Relapsed Multipl Myeloma: Comprasion of Effectivity and Adverse Events

Original versus generic lenalidomide in patients with relapsed multipl myeloma: Comprasion of effectivity and adverse events Ali Zahit Bolaman1, Sehmus Ertop2 Atakan Turgutkaya1, Cem Selim, 1 Ayse Hilal Eroglu Kucukerdiler1, Birsen Sahip2, Irfan Yavasoglu1. 1 Adnan Menderes University, School of Medicine, Department of Hematology AYDIN/TURKEY 2 Bulent Ecevit University School of Medicine, Department of Hematology ZONGULDAK/TURKEY Backround: Lenalidomide is an effective IMID derivative drug in the treatment of patients with multiple myeloma. Lenalidomide is available as original and generic forms in our country. So far, there is no any clinical study comparing generic and original lenalidomine for effectivity and adverse events. We compared generic and original lenalidomide effects and adverse events (AEs) in patients with relapsed multiple myeloma (RMM). Methods: The patients with RMM using original or generic lenalidomide were evaluated as retrospectively. Overall response (OR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease and progressive disease rates and also for adverse events, development rates of neutropenia, anemia, thrombocytopenia, febrile neutropenia, anorexia, constipation diarrhea, nausea, vomiting, creatinine increase, transaminase increase, asthenia, fatigue, pyrexia, peripheral edema, upper respiratory system infection, pneumonia, another infection, muscle cramp, back pain, bone pain, muscle weakness, arthralgia, headache, tremor, paresthesia, deep vein thrombosis, pulmonary embolism, hyperglycemia, hypokalemia, hypocalcemia, hypomagnesaemia, skin dry and skin erythema were investigated in myeloma patients. All data were analyzed using the PASW for Windows version 19.0 (SPSS Inc., Chicago, IL, USA). The results were described as a number, frequency, and percentage. The chi-squared test and Fisher's exact test were used for the analysis of categorical data and independence between variables. The results were assessed at 95% confidence interval and p-value of less than 0.05 was accepted as significant. Results: The number of patients using original lenalidomide was 55 and the number of patients using generic lenalidomide was 43. OR rate was 60 % versus 39.5% in patients using original and generic lenalidomide, respectively. CR rate was 14.5%, VGPR was rate 45.4% in original group while CR rate was 20.9 and VGPR 18.6 in patients using generic lenalidomide. AEs were low in original lenalidomide group than generic group. AEs were usually grade 1 or 2. Response and AEs rates are shown in Table 1. Conclusion: Our study showed original and generic forms of lenalidomide are effective for the treatment of RMM. OR rate was higher in original lenalidomide than generic lenalidomide. The AEs of original lenalidomide were lower than generic lenalidomide without statistically significance. Further studies involving a larger number of patients with RMM would be useful for comparing the efficacy and AEs of original or generic lenalidomide. Disclosures No relevant conflicts of interest to declare.

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First Asia-Pacific Co-Operative Multicenter Multiple Myeloma Clinical Trial: Preliminary Results of the “dtZ”/“DAZZLE” Study.

Blood ◽

10.1182/blood.v114.22.4940.4940 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4940-4940

Author(s):

Gerrard Teoh ◽

Kihyun Kim ◽

Alok Srivastava ◽

Vasant Pai ◽

Sung-Soo Yoon ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Conflicts Of Interest ◽

Complete Response ◽

Osteonecrosis Of The Jaw ◽

High Rate ◽

Asia Pacific ◽

Hematopoietic Stem ◽

Asian Patients ◽

Tract Infections

Abstract Abstract 4940 Introduction Many physicians have anecdotally reported that Asian patients with multiple myeloma (MM) are frequently unable to tolerate full doses of dexamethasone (Dex) and/or thalidomide (Thal). Unfortunately, co-operative clinical studies from the Asia-Pacific countries are presently lacking and the effective dose of the Dex/Thal combination in Asians is unknown. Since higher doses of zoledronic acid (Zol) have been shown to exert an anti-MM effect in pre-clinical models of MM, we investigated whether higher frequency dosing of Zol combined with lower doses of Dex/Thal could be an effective and better tolerated regimen in Asian patients. Moreover, since attainment of very good partial response (VGPR), near complete response (nCR) or complete response (CR) prior to autologous hematopoietic stem cell transplantation (AHSCT) correlates with good outcome in MM, we wanted to determine if this lower-dose Dex/Thal with higher-frequency dosing Zol regimen could be a good preparative regimen in transplant-eligible patients. Patients and Methods In this international co-operative multicenter phase II non-randomized single arm study in previously untreated patients with MM (n=44), all patients received up to 6 cycles of three-weekly Dex/Thal/Zol (or “dtZ”). Doses of Dex ranged from 20 mg weekly to 20 mg four times a week; and doses of Thal ranged from 50 mg weekly to 100 mg every night. Zol 4 mg was given three-weekly. Response was graded using Blade's criteria. Results The study population included 67.3% Oriental (Korean and Chinese), 30.8% Indian and 1.9% Malay patients. 15.4% of patients were ISS stage I, 61.5% stage II and 23.1% stage III prior to treatment. 39 (88.6%) patients demonstrated at least a partial response (PR); and 23 (52.3%) of patients achieved VGPR (18.2%), near nCR (15.9%) or CR (18.2%). The fastest time to VGPR/nCR/CR was 1 cycle. Most patients tolerated treatment very well and were managed in the outpatient clinic. Sepsis was the most frequently reported grade 3 or 4 toxicity – 8 (18.2%) patients developed bronchopneumonia, and 3 (6.8%) gastrointestinal or urinary tract infections. 1 (2.3%) patient was suspected of having pulmonary embolism. There were 4 (9.1%) deaths – 3 from severe sepsis and 1 from an unknown cause. Importantly, there were no reports of peripheral neuropathy, osteonecrosis of the jaw (ONJ) or end stage renal failure. In fact, there was an overall 2.4% improvement in the median creatinine clearance time (CCT). Finally, the percentage of CD34 stem cells was not adversely affected by treatment with dtZ. Conclusions The dtZ regimen appears to be an effective and well-tolerated treatment regimen for Asian patients with newly-diagnosed MM. The high rate of VGPR/nCR/CR will greatly facilitate AHSCT in transplant-eligible patients. Judicious use of low-dose Thal has abrogated the numerous side-effects associated with Thal and greatly improved patient tolerance. Even though Zol is administered at a higher frequency, it is not associated with worsening of renal function or ONJ. Infections are the most frequent and worrisome complications of treatment. These are likely to be related to the dose of Dex. Accordingly, it is probably wise to further lower the dose of Dex in future studies. (This study is registered with NIH PRS # 00263484.) Disclosures No relevant conflicts of interest to declare.

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Prevalence of Oligoclonal Bands in Multiple Myeloma Patients Who Achieved Better Results Than Very Good Partial Response after Treatment with Standard or High Doses Chemotherapy-Final Analysis

Blood ◽

10.1182/blood.v126.23.4210.4210 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4210-4210

Author(s):

Luiza soares Vieira ◽

Edvan de queiroz Crusoe ◽

Manuella de S. Sampaio Almeida ◽

Lais Sousa ◽

ana Lucia Perez ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Conflicts Of Interest ◽

Progression Free Survival ◽

Final Analysis ◽

Complete Response ◽

High Dose Chemotherapy ◽

Oligoclonal Bands ◽

High Dose ◽

Good Partial Response

Abstract Introduction - Oligoclonal bands (OB) are monoclonal proteins distinct from those originally identified in the multiple myeloma (MM) diagnosis. Some authors consider that appearance of these bands confers a better prognosis and may be linked to immune reconstitution. There is no data of the exact prevalence of OB emergence in patients with very good partial response (VGPR) or better after different treatment schedules. Objectives - To determine the prevalence of OB in MM patients treated with or without high-dose chemotherapy that obtained at least VGPR and its prognostic value. Methods- This is a retrospective and prospective cohort study. Data were collected from records of patients that achieved at least VGPR to identify the OB emergence. Subsequently, new sample collections from the positive patients were made in order to monitor the progress and duration of the maintenance of these bands. Results-Median follow-up was 42m and 101 patients were included. Median age was 58y (29-87) and 55% were male. IgG was the most frequent component (60%). Durie-Salmon IIIA/B was identified in 92% of the population; ISS was 33% in stage I, 30% in stage II, and 31% in stage III. The prevalence of OB identified by SPE and IF was 50.5% (51 cases), with a higher prevalence in those who underwent transplantation and those who achieved complete response (p=0.00139 and p=0.0368, respectively). Progression free survival (PFS) was longer in the OB group (45.4m x 34.7m p = 0.0075). Conclusion - The OB prevalence in this population was 50.5% and oligoclonality resulted in a longer PFS. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials

Frontiers in Pharmacology ◽

10.3389/fphar.2021.758992 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yali Tao ◽

Hui Zhou ◽

Ting Niu

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Adverse Events ◽

Response Rate ◽

Complete Response Rate ◽

Meta Analysis ◽

Complete Response ◽

Cochrane Central Register ◽

Safety And Efficacy ◽

Grade 3

Background: Selinexor (SEL) is an orally bioavailable, highly-selective, and slowly-reversible small molecule that inhibits Exportin 1. Preclinical studies showed that SEL had synergistic antimyeloma activity with glucocorticoids, proteasome inhibitors (PIs) and immunomodulators. The combination of selinexor and dexamethasone (DEX) has been approved in the United States for patients with penta-refractory multiple myeloma in July 2019. This meta-analysis aimed to investigate the safety and efficacy of selinexor based treatment in Multiple myeloma.Methods: We systematically searched the Medline (PubMed), Embase, Web of Science, Cochrane Central Register of Controlled Trials Library databases and ClinicalTrials.gov. Outcome measures of efficacy included overall response rate (ORR), clinical benefit rate (CBR), stringent complete response rate (sCR), complete response rate (CR), very good partial response (VGPR), partial response rate (PR), minimal response (MR), rate of stable disease (SDR), rate of progressive disease (PDR) and median progression-free survival (mPFS). Safety was evaluated by the incidences of all grade adverse events and Grade≥3 adverse events. The subgroup analysis was conducted to analyze the difference in different combination treatment regimens (SEL + DEX + PIs vs SEL + DEX).Results: We included six studies with 477 patients. The pooled ORR, CBR, sCR, CR, VGPR, PR, MR, SDR, and PDR were 43% (18–67%), 55% (32–78%), 5% (−2–13%), 7% (4–11%), 14% (5–24%), 23% (15–31%), 11% (8–14%), 26% (14–38%) and 14% (4–23%), respectively. SEL + DEX + PIs treatment had higher ORR (54 vs 24%, p = 0.01), CBR (66 vs 37%, p = 0.01), sCR (10 vs 2%, p = 0.0008), and VGPR (23 vs 5%, p < 0.00001) compared to SEL + DEX treatment, and lower PDR (4 vs 23%, p < 0.00001) and SDR (17 vs 37%, p = 0.0006). The pooled incidences of any grade and grade≥3 were 45 and 30% in hematological AEs, and in non-hematological AEs were 40 and 30%, respectively. The most common all grade (68%) and grade≥3 (54%) hematological AE were both thrombocytopenia. Fatigue was the most common all grade (62%) and grade≥3 (16%) non-hematological AE. Compared to SEL + DEX treatment, SEL + DEX + PIs treatment had lower incidences of hyponatremia (39 vs 12%, p < 0.00001), nausea (72 vs 52%, p < 0.00001), vomiting (41 vs 23%, p < 0.0001), and weight loss (42 vs 17%, p = 0.03) in all grade AEs. Meanwhile, SEL + DEX + PIs treatment had lower incidences of anemia (36 vs 16%, p = 0.02), fatigue (20 vs 13%, p = 0.04), hyponatremia (22 vs 5%, p < 0.0001) than SEL + DEX treatment in grade≥3 AEs.Conclusion: Our meta-analysis revealed that selinexor-based regimens could offer reasonable efficacy and tolerable adverse events in patients with multiple myeloma. SEL + DEX + PIs treatments had higher efficacy and lower toxicities than SEL + DEX.

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Efficacy and Safety of Histone Deacetylase Inhibitors in Multiple Myeloma - a Systematic Review of Early Phase Clinical Trials

Blood ◽

10.1182/blood-2018-99-114019 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5629-5629

Author(s):

Sharoon Samuel ◽

Muhammad Junaid Tariq ◽

Muhammad Usman ◽

Amna Khalid ◽

Muhammad Asad Fraz ◽

...

Keyword(s):

Systematic Review ◽

Multiple Myeloma ◽

Clinical Trials ◽

Adverse Events ◽

Phase I ◽

Hdac Inhibitors ◽

Complete Response ◽

Number Of Patients ◽

Grade 3 ◽

Early Phase Clinical Trials

Abstract Introduction Recent studies in novel therapies have created opportunities for new treatment regimens to be used in the management of multiple myeloma. Histone deacetylase (HDAC) inhibitors lead to epigenetic manipulation of multiple myeloma (MM) cells by reducing resistance to pro-apoptotic signals. Panobinostat is an FDA approved HDAC inhibitor for multiple myeloma. The aim of this article is to study the safety, efficacy and dose limiting toxicities of HDAC inhibitors in the early phase clinical trials in multiple myeloma. Methods We performed a comprehensive literature search for phase I & I/II trials of HDAC inhibitors during last ten years using following databases: PubMed, Embase, AdisInsight, and Clinicaltrials.gov. Studies involving HDAC inhibitors in multiple myeloma other than panobinostat irrespective of the age, sex or specific eligibility criteria were included. Results Out of 2537 studies, we included 25 trials (23 phase I, 2 phase I/II) of HDAC inhibitors in this systematic review having a total of 518 patients. Of these, 471(90.9%) patients were evaluable for response. Vorinostat (Vor) is the most studied drug used in 13 trials (n=281). Two trials had Vor-only regimen and the remaining 11 had combination regimens mostly with lenalidomide and bortezomib. Vor, in combination with lenalidomide (R), bortezomib (V) and dexamethasone (d) has showed 100% overall response rate (ORR) in 30 newly diagnosed multiple myeloma (NDMM) patients, (Kaufmann et al., 2016), fifty two percent patients achieved very good partial response (VGPR) and 28% patients showed complete response (CR). Another study using Vor + R regimen after autologous stem cell transplant in 16 NDMM patients showed VGPR in 7, stringent complete response (sCR) in 4, partial response (PR) in 2 and CR in 3 patients (Sborov et al.). Grade 3 neutropenia was seen in 1 patient in this study. Richter et al, 2011 showed an ORR of 24% in 29 relapsed refractory multiple myeloma (RRMM) patients with Vor only regimen. Another study (Kaufmann et al., 2012) with Vor only regimen used in 10 RRMM patients showed stable disease (SD) in 9 and minimal response (MR) in 1 patient. ORR of 65% was achieved in 31 RRMM patients receiving Vor in combination with doxorubicin & bortezomib (Vorhees et al, 2017). Thrombocytopenia & neutropenia were reported in 94% and 59% patients respectively. Ricolinostat in combination with Rd and Vd achieved an ORR of 55% and 29% respectively in two studies with 38 and 57 evaluable patients (NCT01583283, NCT01323751). Another ricolinostat regimen with pomalidomide & dexamethasone achieved ≥PR in 6/11 RRMM patients (Madan et al., 2016). Table 1 illustrates the efficacy, number of patients and regimens used in all the studies in this systematic review. Quisinostat in a 2017 study by Moreau P et al. (NCT01464112) showed an ORR of 88% in a combination regimen with Vd in RRMM patients (N=18). Drug related adverse events were seen in 13 patients, thrombocytopenia being most common in 11 patients, 2 patients had grade 3 cardiac disorders and 1 patient had a cardiac arrest. Romidepsin in a phase I/II study (Harrison et al., 2011) combined with Vd was used in 25 RRMM patients. ORR was 60% with VGPR n=7, CR n=2, PR n=6, SD n=5 and PD n=1. Grade ≥3 thrombocytopenia in 16, neutropenia in 9 and peripheral neuropathy in 2 patients was seen. Popat et al used combination of two HDAC inhibitors CHR 3996 and tosedostat in 20 RRMM patients. ORR was 10% and SD was seen in 30% patients. Grade 3/4 toxicities seen were thrombocytopenia (n=12), leukopenia (n=6) and diarrhea (n=5). A phase I study on AR-42 drug in 17 RRMM patients (Sborov et al., 2017) showed SD in 10, PD in 4, MR in 3 patients with progression free survival (PFS) of 8.2 months. Thrombocytopenia, neutropenia and lymphopenia were seen in 11, 10 and 6 patients respectively. A detail of all grade 3 and higher adverse events along with dose limiting toxicity is given in table 2. Three trials (NCT02576496, NCT01947140, NCT03051841) of Edo-S101, romidepsin and CKD-581 are currently recruiting with 84, 93 and 18 planned number of patients. Conclusion Regimens containing vorinostat have shown an ORR up to 100% in NDMM patients. HDAC inhibitors have also shown promising efficacy up to 88% ORR in RRMM population. Majority of the patients developed cytopenias as hematological adverse events. Disclosures No relevant conflicts of interest to declare.

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Bortezomib, Doxorubicin and Dexamethasone (PAD) Combination Therapy for Chinese Relapsed or Refractory Multiple Myeloma.

Blood ◽

10.1182/blood.v114.22.4948.4948 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4948-4948

Author(s):

Yongqing Zhang ◽

Guangxun Gao ◽

Jishi Wang ◽

Xiequn Chen

Keyword(s):

Multiple Myeloma ◽

Peripheral Neuropathy ◽

Partial Response ◽

Combination Therapy ◽

Response Rate ◽

Conflicts Of Interest ◽

Complete Response ◽

Extramedullary Plasmacytoma ◽

Refractory Multiple Myeloma ◽

Progression Of Disease

Abstract Abstract 4948 Objective To investigate the efficacy and safety of PAD (bortezomib, doxorubicin and dexamethasone) combination therapy for Chinese relapsed or refractory multiple myeloma (MM). Methods 31 patients with relapsed or refractory MM received two to eight 21-days cycles of PAD: comprising an intravenous bolus of bortezomib 1.3 mg/m2 (P1,N=13) or 1.0 mg/m2 (P2,N=18) on days 1, 4, 8, and 11, doxorubicin 10mg per day on days 1 to 4, along with dexamethasone 40mg on days 1-4. Response to PAD was evaluated according to International Myeloma Working Group Criteria (IMWG 2006), toxicity was graded according to NCI CTCAE v3.0. Results 25 patients (80.6%) achieved at least a partial response (PR), including complete response (CR) in 9 patients (29%), very good partial response (VGPR) in 7 patients (22.6%), PR in 9 patients (29%) and stable disease (SD) in 4 patients(12.9%), progression of disease (PD) in 2 patients (6.5%); median time to progression was 9.2 months, the median courses to achieve at least PR was 1.6(1-3) cycles, all of 7 patients with extramedullary plasmacytoma achieved at least PR after the first cycle of PAD, extramedullary plasmacytoma disappeared with 1-2 cycles of PAD. The efficacy was independent of traditional prognostic factors such asβ2-MG, Albumin,LDH and Hemoglobin which have previously influenced response to traditional chemotherapy. 1.5 year OS (Overall survival)of CR+VGPR group and PR group were 87.5% vs 46.7% (P=0.09). ≥PR response rate (CR +VGPR +PR) of P1AD and P2AD were 84.6% VS 77.8% (P= 0.501), CR+VGPR rate of P1AD and P2AD were 53.8% vs 50.0% (P=0.561 ). 1 year PFS(Progession-free survival) of P1AD and P2AD were 61.2% vs 55.6%(P=0.638), there were not difference between P1AD and P2AD in response rate(P= 0.501) and 1 year OS (P=0.872). Adverse events included thrombocytopenia in 15 patients ( 48.4% ), leukopenia in 8 patients(25.8%), peripheral neuropathy in 6 patients (19.4% ), varicella herpes zoster in 7 patients (22.6%), fatigue in 11 patients (35.5%) and diarrhea in 5 patients (16.1%), Thrombocytopenia and peripheral neuropathy of P1AD and P2AD were 46.2% vs 11.1%( P=0.037)and 53.8% vs 11.1%(P= 0.014).Common adverse reactions could be controlled with routine supportive treatmemt, one patient (3.2% ) died from respiratory failure during his fifth P1>AD. Conclusions PAD should be considered an appropriate treatment for Chinese relapsed or refractory MM, especially for MM with extramedullary plasmacytoma, its efficacy were independent of traditional prognosis factors, bortezomib dose reduction may reduce toxicities of PAD while retaining the efficacy. Disclosures No relevant conflicts of interest to declare.

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Association Of Stringed Response and Immunoparesis Normalization After Bortezomib-Based Therapy Is Related To Better Outcomes In Multiple Myeloma

Blood ◽

10.1182/blood.v122.21.5354.5354 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5354-5354

Author(s):

Marcio M Andrade Sr. ◽

Ilda Murillo-Florez ◽

Anel Montes-Limon ◽

Beatriz de Rueda ◽

Jose-Maria Grasa ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Conflicts Of Interest ◽

Retrospective Chart Review ◽

Standard Of Care ◽

Complete Response ◽

Response To Therapy ◽

First Line ◽

Female Ratio

Abstract Background Proteasoma inhibitors have proven to be one of the major advances on multiple myeloma (MM) therapy. Their principal effect in growth inhibition of MM cells is achieved not only through the inhibition of proteasomes but also by preventing the adhesion of myeloma cells to stromal cells, induction of cytokines by the microenvironment, decrease angiogenic activity and a direct apoptotic effect on MM cells. Actually it is part of the first-line standard of care therapy for patients with MM. On the other hand, multiple strategies have been developed for trying to predict response or improve the assessment of response and follow-up of MM patients. Currently, the International Myeloma Working Group (IMWG) criteria of response include immunophenotype and immunoparesis analysis. The HevyLiteTM and FreeLiteTM assays (The Binding Site Ltd. Birminghan. UK) permit a separate quantification of the amount of kappa- and lambda-bound to a given immunoglobulin (HLC) and the free light chains kappa or lambda amount quantification (FLC), both being excellent tools for immunoparesis assessment. Aims To analyze the usefulness of immunoparesis analysis by HevyLiteTM and FreeliteTM in patients who receive bortezomib-based therapy in our institution. Patients and Methods A retrospective chart review was performed including the patients diagnosed with secretor IgA or IgG MM who received therapy with bortezomib either at relapse or as first-line therapy. General clinical characteristics, therapy schedules, number of cycles, response to therapy according IMWG criteria and relapse were recorded. For the analysis, only patients with at least 4 cycles of bortezomib based regimen and HLC and/or FLC analysis performed between 4-12 weeks after complete therapy were included. Period of study: June 2004 to April 2013. Results At the end of study a total of 67 MM patients had received bortezomib-based therapy, 63 of them completed 4 or more cycles and were included in the analysis. Male/Female ratio: 31/32, mean age: 66.9 years old (46-81), therapeutic schedules were: bortezomib-prednisone: 3 (4.7%), bortezomib-dexametasone: 33 (51.6%), bortezomib-melfalan-prednisone: 18 (28.1%), bortezomib-dexametasone-lenalidomide: 8 (12.5%) and bortezomib-talidomide-dexametasone: 1 (1.6%). 55% of patients received at least 6 cycles of therapy. Immunoglobulin Myeloma subtype: IgAL: 13 (20.4%) patients, IgAK: 10 (15.6%) patients, IgGK: 32 (50.8%) patients and IgGL: 8 (14.1%) patients. A total of 46 (73%) patients showed an abnormal HLC ratio at diagnosis and 48 (76,2%) had immunoparesis before therapy; a total of 47 (74.6%) registered an abnormal FLC ratio at diagnosis. The response to therapy was: 15 (23.8%) of cases achieved a stringent complete response (SR), 3 (4.8%) a very good partial response (VGPR), 36 (57.1%) obtained a partial response (PR) and 9 (14.3%) patients had not-response/progressive-disease. At the time of post-therapy evaluation, 26 (37%) of patients had normalized FLC-ratio, 15 (23.8%) maintain the SR, 1 (1,6%) patient in VGPR and 5 (11.1%) in PR and 1 (1.6%) of non-responder patients. Normalization of HLC-ratio was only observed in patients with SR and VGPR: 13 (20.6%). Regarding the immunoparesis analysis, only 15 (23.8%) of patients with immunoparesis recovered the immune restitution (IR) at the end of therapy, of which 8 (11.7%) were SR patients, 2 VGPR and 5 PR patients. At the end of the study 47(71.4%) patients relapsed, 5 (11.11%) are on maintenance therapy and 11(17.4%) after a median follow-up of 29 months (9-94) without therapy not-relapsed; the association of SR with IR was related to a less tendency to relapse and need of therapy, 7/8 patients who achieved this status are not-relapsed. Conclusion In our cohort, patients who achieved a SR with a normalization of immunoparesis shows a clear tendency to less incidence of relapse; probably reflecting a better response with not only an undetectable monoclonal protein but also the recovery of the immune function. Even in small cohorts, the immunoparesis recovery analysis through HLC quantifications seems to be an useful tool to determine a new level of response. More investigations on this field are warranted. This work has been partially supported by a grant from Fundación para el Estudio de la Hematología y hemoterapia en Aragón (FEHHA) Disclosures: No relevant conflicts of interest to declare.

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Autologous Hematopoietic Progenitor Cell Transplant in Patients with Multiple Myeloma in Hospital Central Sur De Alta Especialidad in Petróleos Mexicanos

Blood ◽

10.1182/blood.v124.21.5912.5912 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5912-5912

Author(s):

Patricio Azaola

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Progenitor Cell ◽

Conflicts Of Interest ◽

Autologous Transplantation ◽

Complete Response ◽

Hematopoietic Progenitor Cell ◽

Cell Transplant ◽

Hematopoietic Progenitor ◽

Petroleos Mexicanos

INTRODUCTION Multiple Myeloma (MM) is a clonal B cells disorder producing an accumulation of plasmatic abnormal cells and abnormal light or heavy immunoglobulines. The onset of multiple myeloma is usually insidious, and the subclinical phase may vary in duration from 1 to 3 years. Bone pain is the most frequent initial feature and 60% of patients present with this symptom. Other clinical features may result from anaemia, uraemia, hypercalcaemia, infections, paraplegia, hyperviscosity syndrome and sensorimotor peripheral neuropathies. It accounts for approximately 1% of all neoplastic diseases and 10% of haematological malignancies. The sex incidence of myeloma is approximately equal until the age of 65 years, after which it is somewhat more common in men than in women. The incidence is approximately 3.8 per 100,000 population, it is lower in the white than the black population. In the last decades different treatments have been described with 60 to 80% of complete response, nevertheless disease free survival rate goes from 22 to 50% in the best treatment international centers. That is why autologous transplantation has been used in patients below 65 years old with very good response. OBJECTIVE Describe the experience of patients treated with autologous hematopoietic progenitor cell transplant with diagnosis of Multiple Myeloma in Hospital Central Sur de Alta Especialidad de Petróleos Mexicanos (PEMEX). MATERIAL AND METHODS We analyzed clinical data of patients with diagnosis of Multiple Myeloma that were transplanted from april 2008 to may 2014. RESULTS Ten patients were studied, three of them were over 65 years. Only 7 patients were considered for autologous hematopoietic progenitor cell transplantation, there ages were from 40 to 55 years with a median of 46 years. Transplants were performed from april 2008 to may 2014, 66% were men and 34% women. 66% were IgG and 18% IgA. Presence of Bence-Jones protein without monoclonal peak was found in 16% of the patients. In regard to prognosis index 66% were ISS-I and 34% were ISS-I. Cytogenetic studies were not performed because we did not have molecular cytogenetics so we could not perform the usual FISH translocations described in this disease. One hundred percent of the patients received the first line treatment with dexamethasone, cyclophosphamide, thalidomide and bortezomib. Only one patient received radiotherapy because he had a tumor in the leg, before the transplant was done 68% had complete response and 16 % partial response. Six autologous transplants were doned with conditioning by giving melphalan 200 mg/m2 orally because we did not have IV presentation. The 7 transplanted patients are alive and 71% had complete response and 29% had partial response. Patients that were transplanted responded 11 or 12 days after the transplant. CONCLUSIONS Patients with multiple myeloma that were transplanted were below 46 years, there were below the age reported in the literature, the predominant gender was masculine (2:1). The majority was IgG. The overall survival after the transplant was 40 months (72-6), the most common complication associated to transplant was fever and neutropenia and only in 16% of the patients we could isolate the germ. The patients are currently alive and in complete remission until june 2014. We think that this is the most adequate actual treatment for patients with Multiple Myeloma. We found in the literature that lenalidomide, carfilzomib and dexamethasone may achieve the same response that autologous hematopoietic cell transplant but the results are still in intense investigation. Disclosures No relevant conflicts of interest to declare.

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Thalidomide in Multiple Myeloma - A Community Hospital Experience.

Blood ◽

10.1182/blood.v106.11.5140.5140 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5140-5140 ◽

Cited By ~ 1

Author(s):

Homayoun Leon Daneschvar ◽

Hamed Daw ◽

Asif Chaudhry ◽

Harris Taylor ◽

Manmeet Ahluwalia ◽

...

Keyword(s):

Multiple Myeloma ◽

Side Effects ◽

Partial Response ◽

Community Hospital ◽

Response Rate ◽

Complete Response ◽

M Protein ◽

Newly Diagnosed ◽

Number Of Patients

Abstract Multiple Myeloma accounts for 10% of malignant hematologic neoplasms. For the past 30 years, a combination of melphalan and prednisone has been the standard treatment for this disease. Nonetheless, it remains an incurable malignancy with a median survival that does not exceed three years. Recent evidence suggests that angiogenesis is increased in multiple myeloma and has prognostic value. Because of its anti-angiogenic properties, thalidomide has been employed as therapy and several trials show that thalidomide alone is active in 25% to 35% of patients with relapsed and refractory myeloma. Among previously untreated patients with more advanced and symptomatic disease, the combination of thalidomide-dexamethasone doubled the response rate to 72 % (in comparison to thalidomide alone) and induced remissions more rapidly. Objectives: To evaluate the efficacy and side effects of thalidomide in combination with glucocorticoid in previously untreated (newly diagnosed) and treated (refractory to other chemotherapies) multiple myeloma patients in a community hospital setting. Patients and Methods: We retrospectively identified eighty-four consecutive patients with multiple myeloma treated between September 1999 and October 2004 at the Cleveland Clinic Center at Fairview Hospital. The sixteen of eighty-four patients (Table 1) who had received thalidomide were selected for further study. The median starting dose was 150 mg/d. The maintenance dosage was 50–100 mg/d in accordance with tolerability. In addition to thalidomide all sixteen patients were receiving dexamethasone. All provided written informed consent prior to receiving treatment. The primary end point of the study was response rate, defined as complete (undetectable monoclonal M protein in the serum) or partial (greater than 50% reduction in serum monoclonal M protein level) Results: Three patients achieved a partial response in the refractory group and 2 in the newly diagnosed group. One patient achieved a complete response in the refractory group and four in newly diagnosed patients. Sixty percent of the patients in the refractory group and 100% of the newly diagnosed patients survived the follow up time (Table 2). Major side effects included sedation in four (25%), deep venous thrombosis in three (18.7%), neuropathy in three (18.7%) and constipation in two (12.5 %) of the patients. Conclusion: The combination of thalidomide and dexamethasone appears to show promising activity in patients with newly diagnosed and possibly with refractory MM. The combination induced a high frequency of response, rapid onset of remission, and low incidence of serious irreversible toxicity. However, ongoing randomized trials are still needed to define further the role of thalidomide with dexamethasone in the treatment of multiple myeloma. Table 1 Patients Characteristics Refractory patients Newly diagnosed patients Number of patients 10 6 Age (years) 66.3 60.5 Sex 7 male, 3 female 1 male, 5 female IgA type 3 3 IgG type 6 2 Biclonal 1 1 Table 2 Refractory patients Newly diagnosed patients Partial response 3 2 Complete response 1 4 No response 6 0 Median follow up (months) 25.2 11.3 Median progression free survival (months) 7.5 10 Diagnosis to start of thalidomide (months) 18.7 2.5 Time on thalidomide (months) 14.2 11.2 Number of deaths (during follow up time) 4 0

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Clinical Efficacy of a Bortezomib, Cyclophosphamide and Dexamethasone Compared with Bortezomib, Cyclophosphamide, Thalidomide and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma

Blood ◽

10.1182/blood.v118.21.1868.1868 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1868-1868

Author(s):

Jae-Sook Ahn ◽

Deok-Hwan Yang ◽

Joon Ho Moon ◽

Sang Kyun Sohn ◽

Sung-Hoon Jung ◽

...

Keyword(s):

Multiple Myeloma ◽

Herpes Zoster ◽

Partial Response ◽

Adverse Events ◽

Conflicts Of Interest ◽

Sensory Neuropathy ◽

Salvage Regimen ◽

Refractory Multiple Myeloma ◽

Grade 3 ◽

Acyclovir Prophylaxis

Abstract Abstract 1868 Backgrounds & Aims: Salvage therapy such as bortezomib, cyclophosphamide, thalidomide and dexamethasone (Vel-CTD) showed an effective regimen in patients with relapsed or refractory multiple myeloma (MM). However, toxicities of this regimen due to combination bortezomib and thalidomide interrupt the consecutive treatments in a few patients. Therefore, we compared the clinical responses and toxicities between bortezomib, cyclophosphamide and dexamethasone (Vel-CD) and Vel-CTD in patients with relapsed or refractory MM patients, retrospectively. Methods: Eighty-six patients received at least 2 cycles of treatment with Vel-CTD (bortezomib 1.3 mg/m2 i.v. on D1, 4, 8 and 11; cyclophosphamide 150 mg/m2 orally on D1-4; thalidomide 50 mg/day orally every day; and dexamethasone 20 mg/m2 i.v. on D1, 4, 8 and 11 for every 3 weeks) and 67 patients with Vel-CD, which is the same regimen except thalidomide. Vel-CD group was only received low-dose acyclovir for prevention of herpes zoster. Results: 17/67 (25%) and 10/86 (12%) of light chain disease was enrolled in Vel-CD and Vel-CTD group respectively (p=0.027) and there was no statistical difference at baseline demographic and disease characteristics between two groups in the others. The median time from diagnosis to treatment in Vel-CD and Vel-CTD was 15.6 months (range, 2–250 months) and 15.7 months (range, 1–230 months), respectively (p=0.54). The median number of treatment cycles was 6 cycles (range, 2–18) in Vel-CD and 8 cycles (range, 2–24) in Vel CTD group, and the number of cycles delivered was 430 and 678, respectively. The overall response rates (≥PR) of Vel-CD and Vel-CTD group were 88% and 90% ( 49% and 48% of complete response, 9% and 14% of very good partial response, 30% and 28% of partial response), respectively (each, p>0.05). There was no difference in progression free survival (p=0.69) and overall survival (p=0.49). Grade 3 or more hematologic adverse events occurred in the same proportion of patients in the both group. In non hematologic toxicities profiles, Vel-CTD group (14%) showed the higher proportion of grade 3 or more sensory neuropathy compared with Vel-CD group (3%) (p=0.02). Dose adjustment of bortezomib in Vel-CD and Vel-CTD were 40% (27/67) and 41%(35/86), respectively (p=0.96). Two patients (3%) in Vel-CD group received acyclovir prophylaxis developed herpes zoster compared with 17 patients (20%) in Vel-CTD group they were not received acyclovir prophylaxis (p=0.002). Three patients showed thrombotic events (2: pulmonary thromboembolism, 1: acute myocardial infarction) in only Vel-CTD group despite aspirin prophylaxis (p=0.16). Conclusion: Vel-CD combination therapy in patients with relapsed or refractory MM is an effective and more tolerable salvage regimen compared with Vel-CTD in the aspect of comparable response rate, less non-hematologic toxicities especially thalidomide associated adverse events. Disclosures: No relevant conflicts of interest to declare.

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The Chronic Kidney Disease-Epidemiology Collaboration-Cystatin C (CKD-EPI-CysC) Equation Has an Independent Prognostic Value for Overall Survival in Newly-Diagnosed Patients with Symptomatic Multiple Myeloma: Comparison with 3 Other Equations for GFR Estimation

Blood ◽

10.1182/blood.v120.21.1849.1849 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1849-1849

Author(s):

Meletios A Dimopoulos ◽

Efstathios Kastritis ◽

Eirini Katodritou ◽

Anastasia Pouli ◽

Eurydiki Michalis ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Cystatin C ◽

Prognostic Value ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

P Value ◽

Newly Diagnosed ◽

Number Of Patients ◽

Ckd Stage

Abstract Abstract 1849 Renal impairment (RI) is a frequent complication in multiple myeloma (MM). The estimation of glomerular filtration rate (GFR) is based on equations that use serum creatinine (sCr) as a marker of RI (i.e. MDRD or CKD-EPI). The IMWG has recommended the use of the MDRD formula for the estimation of GFR in MM patients with stabilized sCr, while the classification of RI is based on the 5 stages of the KDIGO classification (Dimopoulos et al, JCO 2010;28:4976–84). However, the equations based on sCr are imprecise and thus novel markers of renal injury have been used in patients with renal damage, including cystatin-C (CysC). CysC is considered as a more sensitive marker of GFR than sCr. Recently, the CKD-EPI investigators have reported that a combined sCr-CysC (CKD-EPI-sCr-CysC) equation correlated better with GFR than equations based on either of these markers alone (CKD-EPI or CKD-EPI-CysC; Inker et al, NEJM 2012;367:20–9). Although cysC has been reported by our group to be elevated in MM patients, the CKD-EPI equations and their value on MM patients' survival have never been evaluated. Therefore, we studied 220 newly-diagnosed, previously untreated, symptomatic MM patients. The median age was 69 years (range: 36–94 years) and 16% had sCr ≥2 mg/dl. Serum CysC was measured on the BN ProSpec analyser using a latex particle-enhanced nephelometric immunoassay (Dade Behring-Siemens Healthcare Diagnostics, Liederbach, Germany). Serum CysC was increased in MM patients compared to 52 age- and gender-matched controls [median: 1.07 mg/l vs. 0.72 mg/l, p<0.0001]. The median values for eGFR calculated by the MDRD, CKD-EPI, CKD-EPI-CysC and CKD-EPI-sCr-CysC equations were 63.45 ml/min/1.73m2, 68.13 ml/min/1.73m2, 68.11 ml/min/1.73 m2, and 64.87 ml/min/1.73 m2, respectively (p<0.01). Patients were divided in the 5 CKD stages of KDIGO classification, according to eGFR (stage 1: eGFR >90 ml/min/1.73 m2; stage 2: 60–89 ml/min/1.73m2; stage 3: 30–59 ml/min/1.73 m2; stage 4: 15–29 ml/min/1.73 m2; stage 5: <15 ml/min/1.73 m2 or on dialysis). For each studied equation, the number of patients with RI stage 3–5 (i.e. eGFR <60 ml/min/1.732) was 39.5% for MDRD vs. 42.2% for CKD-EPI vs. 43.1% for CKD-EPI-CysC vs. 45% for CKD-EPI-sCr-CysC (p<0.01; see also the table). Concordance for CKD stage allocation for the 4 equations of estimating eGFR was 97% for MDRD vs. CKD-EPI, 60% for MDRD vs. CKD-EPI-CysC and 84% for MDRD vs. CKD-EPI-sCr-CysC. A significant correlation was found between ISS stage and all studied equations (p<0.01 for all). The median overall survival (OS) for all patients was 52 months. In the univariate analysis per CKD stage, the 4 equations could predict for OS (the higher CKD stage had poorer survival) with the following significance: MDRD (p=0.057), CKD-EPI (p=0.01), CKD-EPI-CysC (p<0.0001), and CKD-EPI-sCr-CysC (p=0.006). When we tested the 4 equations as continuous variables, all had prognostic value for OS but the CKD-EPI-CysC had the strongest prognostic value (p<0.0001 and Wald=24.0 vs. p<0.0001 and Wald=19.7 for CKD-EPI-sCr-CysC, p=0.003 and Wald=8.9 for CKD-EPI and p=0.005 and Wald=7.7 for MDRD). In the multivariate analysis, that included ISS stage, LDH ≥300 U/l and eGFR for each different equation (as a continuous variable) only eGFR that included CysC but not sCr (CKD-EPI-CysC and not CKD-EPI-sCr-CysC) had independent significance (p=0.013) along with high LDH (p=0.029). Our data suggest that the CKD-EPI-sCr-CysC equation for the estimation of GFR detects more MM patients with stage 3–5 RI than the MDRD, CKD-EPI or CKD-EPI-CysC equations. However, CKD-EPI-CysC was the only equation that could predict for OS, possibly due to the very strong correlation of CysC with ISS (as myeloma cells produce CysC also). The confirmation of these data will lead to the broader use of equations based on CysC (CKD-EPI-CysC with or without sCr) for the evaluation of RI in patients with MM, as it has been suggested for patients with several other renal disorders. Table. Evaluation of Renal Function Stage by Different Equations CKD stage MDRD equation CKD-EPI equation CKD-EPI-CysC equation CKD-EPI-sCr-CysC equation p-value 1 60 (27%) 57 (26%) 67 (30%) 44 (20%) 2 73 (33%) 70 (32%) 58 (26%) 77 (35% Friedman-test 3 53 (24%) 55 (25%) 57 (26%) 62 (28%) p<0.01 4 21 (9.5%) 25 (11%) 27 (12%) 24 (11%) 5 13 (6%) 13 (6%) 11 (5%) 13 (6%) Disclosures: No relevant conflicts of interest to declare.

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