Combination Of Thalidomide Research Articles

Cyclosporin A and thalidomide in patients with myelodysplastic syndromes: Results of a pilot study

We reported 37 patients with myelodysplastic syndromes (MDS) of refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts who were treated with cyclosporin A (CyA)/thalidomide combination therapy. Of them, 19 patients (19/37, 51.4%) achieved a hematologic improvement and erythroid response (HI-E); 9 patients (9/29, 31.0%) achieved hematologic improvement and platelet response (HI-P) and 7 patients (7/33, 21.2%) achieved hematologic improvement and neutrophil response (HI-N). 15 of 32 (46.9%) transfusion-dependent patients achieved independence from transfusion. The median response duration of HI-E, HI-P and HI-N were 88 (4–108) weeks, 78 (8–84+) weeks and 78 (10–84+) weeks, respectively. Some patients presented with I or II grade hepatic or nephritic impairment, constipation, lethargy, dizziness, edema, rash or sense of numbness. Therefore, CyA combined with thalidomide appears to be useful and is relatively well-tolerated for patients with MDS.

Early alpha‐fetoprotein response predicts treatment efficacy of antiangiogenic systemic therapy in patients with advanced hepatocellular carcinoma

Antiangiogenic therapy has become the most important treatment modality for patients with advanced hepatocellular carcinoma (HCC). In this study, the authors investigated levels of alpha-fetoprotein (AFP) as a potential biomarker for treatment efficacy of antiangiogenic therapy. Patients with advanced HCC who had been enrolled in 3 prospective phase 2 clinical trials that evaluated either sorafenib, bevacizumab, or thalidomide in combination with a potentially antiangiogenic, metronomic, oral 5-fluoropyrimidine as first-line systemic therapy were included. An early AFP response was defined as a decline >20% from baseline after 2 to 4 weeks of treatment. AFP response was analyzed for its association with treatment efficacy and survival outcome. Seventy-two patients were included for early AFP response evaluation, and 12 of those patients (17%) were classified as early AFP responders. Early AFP responders, compared with nonresponders, had a significantly improved overall response rate (33% vs 8%; P=.037) and a significantly improved disease control rate (83% vs 35%; P=.002), which was defined as the percentage of patients who had an objective response plus stable disease for a minimum of 8 weeks. AFP responders, compared with nonresponders, also had longer median progression-free survival (PFS) (7.5 months vs 1.9 months; P=.001) and longer median overall survival (OS) (15.3 months vs 4.1 months; P=.019). In a multivariate analysis, AFP response remained a significant independent predictor of better PFS and OS. The current results indicated that an early AFP response is a useful surrogate marker to predict treatment response and prognosis in patients with advanced HCC who receive antiangiogenic therapy.

High rate of stem cell mobilization failure after thalidomide and oral cyclophosphamide induction therapy for multiple myeloma

Novel agents are increasingly used during induction therapy for multiple myeloma (MM), but there is concern about their potential impact on stem cell mobilization. Regimens containing either thalidomide or cyclophosphamide have little or no impact on stem cell collection. In this retrospective review of 136 patients with newly diagnosed MM, we show that the combination of thalidomide and oral CY with dexamethasone (CTD) during induction therapy impaired stem cell mobilization substantially. Compared with VAD (vincristine, doxorubicin, dexamethasone) and a VAD-like induction regimen, the stem cell collection yield after CTD was decreased by 49% (median 5.0 vs 9.8 × 10(6) CD34+cells/kg, P<0.001). Following CTD, more patients failed to mobilize enough stem cells for one (25.4 vs 5.8%, P=0.002) or two (39.4 vs 15.9%, P=0.002) transplants. These results demonstrate that the combination of thalidomide and oral CY impairs stem cell mobilization and indicate that drugs with no previously reported relevant effect on stem cell mobilization can have a substantial impact when given in combination.

The efficacy and safety of the low-thalidomide dose CTD (cyclophosphamide, thalidomide, dexamethasone) regimen in patients with multiple myeloma—A report by the Polish Myeloma Study Group

Multiple myeloma (MM) remains an incurable disease, but response rates to new drugs are promising, offering the majority of patients a significant prolongation of overall survival. The objective of this study was to evaluate time to progression (TTP), event-free survival (EFS), and overall survival (OS) in MM patients treated with a combination of cyclophosphamide (CY), thalidomide (THAL) and dexamethasone (DEX). This study included 132 untreated and relapsing/resistant patients treated with the low-thalidomide dose CTD regimen. The patients received CY 500 mg/m 2 i.v. or 625 mg/m 2 orally at day 1, THAL 100 mg/day á la longue and DEX 20 mg/day at days 1–4 and 8–11, every 28 days. Patients received 6–9 cycles; ORR by 3 months was 59.1%, by 6 months 65.6% and by 9 months 75.6%. In patients responding to CTD therapy (CR, nCR, PR), the probability of survival for 20 months was 89.3%. The outpatient low-thalidomide dose CTD regimen is well tolerated and produces a significant response rate both in untreated and relapsing/resistant MM patients.

Management of disease- and treatment-related complications in patients with multiple myeloma

Treatment of myeloma has dramatically changed after introduction of novel agents, such as thalidomide, lenalidomide and bortezomib, with a significant improvement in response rate and survival of patients with myeloma. For newly diagnosed patients not eligible for transplant, the standards of care are now considered melphalan and prednisone (MP) plus thalidomide and MP plus bortezomib. Ongoing randomized trials are evaluating lenalidomide plus MP and lenalidomide plus dexamethasone. For newly diagnosed patients eligible for transplant, new induction regimens included the combination of high-dose dexamethasone plus thalidomide, high-dose dexamethasone plus lenalidomide (RD) and high-dose dexamethasone plus bortezomib (VD). The combinations RD, VD and bortezomib plus pegylated-liposomal-doxorubicin have received the US Food and Drug Administration approval for the treatment of relapsed myeloma. Different efficacious regimens are therefore now available for patients with myeloma. Disease control leads to improvement of all myeloma-related complications (anemia, bone disease, immune dysfunction and renal impairment), but physicians should take into account the choice of the therapeutic strategy, the expected toxicity profile of each of these regimens, together with the patient's biologic age and comorbidities. Supportive care is an essential part of myeloma therapy, both for the treatment of myeloma-related complications, together with anti-myeloma treatment, and for the management of treatment-emergent adverse events. This chapter will provide an overview of frequency and management of main complications related to the disease itself and to the use of new drugs in newly diagnosed and relapsed patients with myeloma.

Arsenic trioxide enhances the cytotoxic effect of thalidomide in a KG-1a human acute myelogenous leukemia cell line

Studies have shown that thalidomide exerts modest activity as a single agent in the therapy of acute myeloid leukemia (AML). The present investigation was conducted to test the hypothesis that the cytotoxic effect of thalidomide is enhanced when properly combined with other chemotherapeutic agents. The human AML cell line KG-1a was used in this study. Cells were cultured for 48 h in the presence or absence of thalidomide, arsenic trioxide and a combination of the two substances. Results obtained indicate that thalidomide at concentrations of 1, 2 and 5 mg/l produced a dose-dependent cytotoxic effect and at 5 mg/ml resulted in late apoptosis in 49.39% of the total cell population (as compared to 5.35% in the control cells). When the cells were incubated with arsenic trioxide alone (4 µM), late apoptosis was detected in 16.97% of the total cell population. However, when cells were incubated with a combination of thalidomide (5 mg/l) and arsenic trioxide (4 µM), late apoptosis was noted to be 80.6% in the total cell population. This percentage of late apoptosis was statistically significant from that observed when cells were incubated with thalidomide alone. These findings clearly indicate that arsenic trioxide enhances the cytotoxic effects of thalidomide.

Erythropoiesis-stimulating agents in the treatment of anaemia in cancer patients: ESMO Clinical Practice Guidelines for use

Erythropoiesis-stimulating agents in the treatment of anaemia in cancer patients: ESMO Clinical Practice Guidelines for use

Abstract 1661: Effect of thalidomide and liposomal doxorubicin on human osteoclastogenesis

Abstract Background: Thalidomide has been reported capable of inhibiting angiogenesis and growth of multiple myeloma. Liposomal doxorubicin is known to be mainly absorbed and degraded in reticuloendothelial system, especially the monocyte-macrophage lineage. Since osteoclasts (OCs) are derived from precursors of monocyte-macrophage lineage, we aimed to examine the effect of thalidomide, liposomal doxorubicin and their combination on human osteoclastogenesis. Materials and Methods: We isolated CD14+ cells from peripheral blood mononuclear cells of healthy subjects and generated OCs under stimulation with macrophage-colony forming factor and receptor activator of NK-κB ligand. Cell viability, surface CD51/61 expression, and tartrate-resistant acid phosphatase (TRAP) activity were assessed by using MTT, flow cytometry and immunohistochemical staining, respectively. Results: In comparison with control differentiated OCs, combination of thalidomide (purchased from TTY Biopharm, Taiwan) and liposomal doxorubicin (purchased from TTY Biopharm, Taiwan) profoundly inhibited the amount of harvested viable OCs. By treatment with each drug alone, thalidomide increased and liposomal doxorubicin decreased the amount of viable OCs. The expression of osteoclast-specific surface antigen CD51/61 was greatly inhibited by each drug and their combination. Furthermore, the amount of multinucleated TRAP-positive cells characteristics of OCs, was suppressed by each drug and, the mostly, their combination. Elucidation of cellular and molecular mechanisms of action has been undergoing. Conclusion: Thalidomide, liposomal doxorubicin and their combination may effectively inhibit human osteoclastogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1661.

A randomized clinical study on combination of concurrent chemo-radiotherapy and thalidomide for middle-late esophageal cancer

Objective To evaluate the response rate and tolerance of patients with middle-late esophageal carcinoma, who were treated with concurrent chemoradiotherapy (CCRT) plus thalidomide.

Consensus guidelines for the optimal management of adverse events in newly diagnosed, transplant-ineligible patients receiving melphalan and prednisone in combination with thalidomide (MPT) for the treatment of multiple myeloma

Thalidomide has received approval from the European Agency for the Evaluation of Medicinal Products for the treatment of newly diagnosed multiple myeloma (MM) patients older than 65 years or ineligible for transplant. The results of five phase III trials assessing thalidomide in combination with melphalan and prednisone (MPT) have demonstrated significantly improved response rates compared with melphalan and prednisone (MP) alone. Additionally, two of these studies showed that survival was extended by approximately 18 months in patients treated with MPT compared with MP alone. Thalidomide, in combination with MP, is associated with adverse events (AEs) including peripheral neuropathy and venous thromboembolism. In order to optimize the efficacy of MPT, a good awareness of these AEs is imperative. This manuscript outlines both evidence- and consensus-based recommendations discussed by a panel of experts, to provide a practical guide for physicians addressing the effective management of newly diagnosed, transplant-ineligible MM patients receiving thalidomide therapy.

Advances in treatment for relapses and refractory multiple myeloma

Recent advances in the treatment of multiple myeloma have resulted in improved response rates and overall survival in patients with multiple myeloma. These advances are largely due to thalidomide-, lenalidomide-, and bortezomib-based combinations that have improved response rates, not only in patients with untreated disease, but also in those with relapsed and/or refractory myeloma, in some cases producing response rates up to 85%. Eventually, however, nearly all patients relapse, emphasizing a continuing role for the introduction of investigational agents that overcome drug resistance. This article will review the current role for thalidomide, lenalidomide, and bortezomib-based combinations, as well as some preliminary findings for promising investigational agents currently in clinical trials for patients with relapsed and/or refractory disease.

The combination of thalidomide, cyclophosphamide and dexamethasone is potentially useful in highly resistant Hodgkin’s lymphoma

Few diseases have a prognosis worse than Hodgkin's lymphoma (HL), patients relapsing after autologous or allogeneic stem cell transplantation. Here, we report two highly refractory patients with HL who successfully responded to a combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex). Despite the use of a very large number of different drugs (>5 different schemes) including high-dose therapy and autologous and allogeneic stem cell transplantation, both patients proved to be suffering from a highly resistant disease. Fortunately, they finally responded to the ThaCyDex combination, achieving sustained complete remission that would support the running of a trial within this setting.

Safety, Tolerability and Biological Effects of Long-Term Metronomic Administration of Non-Cytotoxic Anti-Angiogenic Agents

Background: α-Interferon, thalidomide and celecoxib inhibit tumour angiogenesis by differing mechanisms. Patients and Methods: In a randomized phase II trial to assess tolerability and safety, we assigned patients with advanced slow-growing solid tumours to 1 of 6 two- or three-drug combinations: α-interferon 0.5 million IU b.i.d., thalidomide (100 mg b.i.d. reduced to 100 mg daily), or celecoxib (400 mg daily reduced to 200 mg). Circulating endothelial cells and progenitors (CECs, CEPs) and vascular endothelial growth factor were also studied. Results: From January 2002 to September 2005, 62 patients were enrolled. Four months after initiating treatment, 3 (4%) had partial response, 40 (64%) had stable disease and 19 (30%) had disease progression. Median duration of clinical benefit (partial response/stable disease) was 11.3 months. Patients receiving a third drug had significantly less stable disease plus partial response (χ² test, p = 0.002) than those receiving two drugs. The treatments were generally well tolerated, but neurotoxicity (G3 lethargy) occurred in 6 patients. Baseline CEPs were lower (p = 0.004) in patients with clinical benefit at 6 months than those without benefit. After 2 months of treatment CECs were lower than at baseline (p = 0.018) in patients without clinical benefit, and CEPs were higher than at baseline (p = 0.003) in patients with benefit. Conclusions: In pretreated patients with advanced slow-growing solid tumours, long-term metronomic administration of two-drug combinations of α-interferon, thalidomide or celecoxib was well tolerated and had antitumour activity. Low baseline CEPs in patients with subsequent clinical benefit suggest that CEC count may identify patients likely to benefit from long-term metronomic anti-angiogenic treatment.

A modular Phase I study of lenalidomide and paclitaxel in metastatic castration-resistant prostate cancer following prior taxane therapy

Lenalidomide, a highly potent immunomodulatory derivative of thalidomide, potentiates the action of paclitaxel in vitro against prostate cancer cell lines in co-culture with mononuclear cells. A modular Phase I study of lenalidomide and paclitaxel in men with metastatic castration-resistant prostate cancer (CRPC) was conducted to assess PSA kinetics with lead-in lenalidomide and the feasibility of the combination. Men with metastatic CRPC with prior taxane chemotherapy were planned for single-agent "lead-in" lenalidomide for 21/28 days at dose-levels: -1 (5 mg), 0 (10 mg), +1 (15 mg), +2 (20 mg), +3 (25 mg); followed by lenalidomide at the same dose and schedule in combination with weekly intravenous paclitaxel 100 mg/m(2) over 3 h on days 1, 8, 15 every 28 days utilizing a 3 + 3 dose-escalation design. Dose-limiting toxicity was observed in 4/6 patients with first-cycle combination therapy at the 10 mg dose-level and 3/6 patients at the 5 mg dose-level of lenalidomide, respectively. These included Grade 3 neutropenia precluding planned paclitaxel therapy (n = 3), grade 3 gastrointestinal toxicity (n = 2), chest pain (n = 1) and pulmonary embolism (n = 1). With lead-in lenalidomide, two patients with lymph-node dominant CRPC had a PSA-decline and regression in lymph node disease, respectively. Two of seven evaluable patients had PSA declines by 50% with combination therapy. Progression-free survival was 13 weeks (range 4-35 weeks). The high dose-limiting toxicity rates observed with lenalidomide and weekly paclitaxel require exploration of alternate dose-schedules of the combination in the second-line setting of CRPC. These early observations suggest distinctive toxicity and efficacy outcomes from thalidomide in combination with paclitaxel.

Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial

Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1-4, prednisone at a dose of 1.5 mg/kg also on days 1-4 and thalidomide at a dose of 50-100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1-4 and 1.6, 3.2, or 4.8 g on days 5-35. Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3-4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1-4 followed by 4.8 g p.o. on days 5-35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs.

Treatment outcome of thalidomide based regimens in newly diagnosed and relapsed/refractory non-transplant multiple myeloma patients: a single center experience from Thailand

BackgroundThalidomide based regimen is an effective and well tolerated therapy in multiple myeloma (MM) patients, however, there were a small number of studies written about the results of thalidomide therapy in non-transplant MM patients. We therefore conducted a retrospective study of 42 consecutive patients with newly diagnosed and relapsed/refractory MM treated with thalidomide- based induction regimens followed by thalidomide maintenance therapy.ResultsInduction regimens with thalidomide and dexamethasone, and the oral combination of melphalan, prednisolone and thalidomide were administrated in 22 and 16 patients, respectively. The remaining 4 patients received other thalidomide- containing regimens. Twenty-nine patients received thalidomide as a salvage regimen. Twenty-three out of 26 patients achieving complete remission (CR) and very good partial remission (VGPR) received thalidomide maintenance. Of the 41 evaluable patients, median time of treatment was 21 months (3- 45 months), ORR was 92.7% with a 63.4% CR/VGPR. With a median follow up of 23 months, 3-year- PFS and 3-year-OS were 58.6 and 72.6%, respectively. Median time to progression was 42 months. While 3-year-PFS and 3-year-OS in non-transplant patients receiving thalidomide maintenance therapy were 67 and 80%, respectively.ConclusionsProlonged thalidomide therapy enhanced survival rate and less frequently developed serious toxicity in non-transplant multiple myeloma patients.

Nonspecific Interstitial Pneumonitis after Bortezomib and Thalidomide Treatment in a Multiple Myeloma Patient

Bortezomib, an inhibitor of 26S proteosome, is recently approved treatment option for multiple myeloma. Thalidomide, a drug with immunomodulating and antiangiogenic effects, has also shown promise as an effective treatment in multiple myeloma. Pulmonary complications are believed to be rare, especially interstitial lung disease. Here, we describe a patient with dyspnea and diffuse pulmonary infiltrates while receiving bortezomib and thalidomide in combination with dexamethasone for treatment-naïve multiple myeloma. Bronchoalveolar lavage demonstrated a significant decrease in the ratio of CD4 : CD8 T lymphocytes (CD4/8 ratio, 0.54). Extensive workup for other causes, including infections, was negative. A lung biopsy under video-assisted thorascopic surgery revealed a diagnosis of nonspecific interstitial pneumonitis. The symptoms and imaging study findings improved after initiating steroid treatment. Physicians should be aware of this potential complication in patients receiving the novel molecular-targeted antineoplastic agents, bortezomib and thalidomide, who present with dyspnea and new pulmonary infiltrates and fail to improve despite treatment with broad-spectrum antibiotics.

Bortezomib Successfully Reverses Early Recurrence of Light-Chain Deposition Disease in a Renal Allograft: A Case Report

Light-Chain Deposition Disease (LCDD) frequently recurs after renal transplantation, displaying a pernicious course. Herein we have described a 39-year-old Caucasian man with a history of immunoglobulin G-kappa multiple myeloma who failed two chemotherapy regimens, but ultimately responded to the combination of thalidomide, bortezomib, and dexamethasone followed by high-dose melphalan and autologous stem cell transplantation 3 years prior to transplantation, during which time he showed no evidence of persistent or recurrent disease. At 3 days following spousal living related renal transplantation, he displayed a rapid deterioration of renal function requiring dialysis therapy. This episode failed to respond to empiric antirejection therapy including anti-thymocyte globulin, plasmapheresis, and anti-CD20 monoclonal antibody. Increasing evidence suggested recurrence of LCDD, including positive immunofluorescence staining of basement membranes and vessels for kappa light chains as well as free kappa light chains in his urine and serum. Following suspension of sirolimus, he was initiated on and responded to bortezomib (1.3 mg/m 2) with discontinuation of dialysis within 3 weeks and progressively improving renal function. His maintenance therapy, in addition to six 2-week-long cycles of bortezomib separated by 1-week rest periods, includes cyclosporine (50 mg twice daily), prednisone (10 mg daily), and curcumin (9 g daily). In sum, bortezomib rescue therapy salvaged a spousal renal transplant afflicted with recurrent LCDD.

A National Registry of Patients Diagnosed with Multiple Myeloma in Taiwan.

Abstract 4955 BackgroundThe diagnosis and treatment pattern in actual practice for patients with multiple myeloma has not been described in Taiwan. This is the first national registry survey with the introduction of conventional and novel anti-myeloma therapies in Taiwan. MethodsThe “Multiple Myeloma Observational Study” is a national-based observational registry survey conducted by the Hematology Society of Taiwan. All patients newly diagnosed with multiple myeloma within one year are eligible for inclusion. Information on treatment, treatment response and survival was obtained by medical record review. We report 115 patients with multiple myeloma in Taiwan who were enrolled from January 2006 to December 2008. ResultsThe characteristics of 115 patients were examined according to age, gender and disease stage. The average age was 65 years. The number of male patient was 72 (62.6%); female patient, 43 (37.4%). The proportions of disease stage were: stage I, 14 (12.2%); stage II, 26 (22.6%); stage III, 75 (65.2%). All patients had received anti-myeloma agents as their first line treatment since diagnosis. The most commonly used regimen was combination of melphalan, prednisolone and thalidomide in 27 patients (23.5%) and combination of thalidomide and dexamethasone in 27 patients (23.5%); followed by combination of melphalan and prednisolone, 24 (20.9%); combination of vincristine, anthracycline and dexamethasone (VAD), 15 (13%), thalidomide alone, 9 (7.8%); dexamethasone alone, 5 (4.3%); combination of VAD and thalidomide, 2 (1.7%); others, 3 (2.6%). The adjunct therapies along with first line treatment include zoledronic acid, 59 (51.3%); clodronate, 16 (13.9%); pamidronat, 8 (7.0%); and epoietin, 5 (4.3%). The outcomes of treatment were also recorded. The overall response rate for first line treatment was 59.1%. The best response of combination of VAD and thalidomide was 100%, followed by combination of thalidomide and dexamethasone, 66.7%; combination of melphalan and prednisolone, 66.7%; the combination of melphalan, prednisolone and thalidomide, 63%, combination of vincristine, anthracycline and dexamethasone, 60%; thalidomide alone, 22.2%; dexamethasone alone, 20%.A total of 31 patients had received anti-myeloma agents as the second line treatment. The most commonly used treatment was thalidomide alone, received by 7 patients (22.6%); followed by combination of thalidomide and dexamethasone, 5 (16.1%); combination of melphalan, prednisolone and thalidomide, 5 (16.1%); VAD, 5 (16.1%); combination of melphalan and prednilolone, 3 (9.7%); dexamethasone alone, 3 (9.7%) and other regimen, 3 (9.7%). The overall response rate for second line treatment was 41.9%. The best response of the combination of melphalan, prednisolone and thalidomide, 66.7%, followed by combination of vincristine, anthracycline and dexamethasone, 60%; thalidomide alone 57.1%; the combination of thalidomide and dexamethasone, 40%. The median survival duration was still not achieved yet. ConclusionsThe results of this national registry show that the choice of treatments in multiple myeloma covers a wide range of therapeutic modality. The overall response of first line treatment and second line treatment was comparable to the result of other registry studies. DisclosuresChiou:Janssen-Cilag Taiwan: Honoraria, Research Funding. Lin:Janssen-Cilag Taiwan: Honoraria. Chang:Janssen-Cilag Taiwan: Honoraria. Hsiao:Janssen-Cilag Taiwan: Honoraria.

The Combination of Cyclophosphamide and Thalidomide During Induction Therapy for Multiple Myeloma Results in a High Rate of Stem Cell Mobilization Failure.

Abstract 2147Poster Board II-124In the era of novel therapeutic agents, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remains an integral component of treatment for multiple myeloma (MM), with a proportion of patients undergoing more than one ASCT during the course of their disease. Therefore, the choice of new drug combinations for induction therapies must take into consideration the requirement to collect a sufficient number of stem cells, which is also reflected in a recently published consensus perspective of the International Myeloma Working Group. The immunomodulatory drug Lenalidomide and the alkylating agent Melphalan have a substantial impact on stem cell mobilization, but the effect of induction therapies containing either Thalidomide or Cyclophosphamide on the stem cell collection yield is negligible. We considered the possibility that the combination of Cyclophosphamide and Thalidomide, which is widely used as an induction regime particularly in the UK as part of the CTD regime (with Dexamethasone), could have an additive impact on the stem cell pool and cause mobilization failures. We carried out a retrospective analysis of the outcome of peripheral blood stem cell mobilizations in MM patients performed at our institution over a four-year period in patients who had received CTD (n=55), and compared them with a control group of patients (n=56) who had received VAD (Vincristine, Doxorubicin, Dexamethasone; n=30) or Z-Dex (Idarubicin, Dexamethasone; n=26) during the same period. There were no differences between the CTD and control group in terms of age, MM subtype, disease stage, or remission status at the time of stem cell mobilization. All mobilizations were performed with Cyclophosphamide (4g/m2) and G-CSF (5-10μg/kg). Apheresis was attempted when the peripheral blood CD34 count was >10 × 103/ml, and the standard harvest target was 4 × 106 CD34+ cells/kg, with a minimal target of 2 × 106 CD34+ cells/kg. The total number of CD34+ cells harvested was substantially lower in the CTD group (5.2 vs. 9.7 × 106/kg, p=0.002), and a higher number of patients in the CTD group underwent more than one apheresis procedure (52.8% vs. 32.1%, p=0.012). The number of CD34+ cells harvested on the first day of apheresis and per apheresis procedure were also lower in the CTD group (2.8 vs. 7.3 × 106/kg, p=0.002; 2.6 vs. 6.7 × 106/kg, p=0.002). More patients in the CTD group failed to achieve both the standard (36.4% vs. 16.1%, p=0.021) and minimal (19.2% vs. 5.4%, p=0.036) stem cell harvest target. The failure rate on the first day of apheresis was also higher in the CTD group both for the standard (56.3% vs. 28.6%, p=0.003) and the minimal target (36.7% vs. 16.1%, p=0.041). There was no difference in stem cell yield between the VAD and Z-Dex groups. Age and number of induction chemotherapy cycles did not have an impact on mobilization failure in the entire cohort or the CTD group alone. In the CTD group, 18% of patients underwent re-mobilization with Etoposide (1.6g/ m2) and G-CSF (n=8), or with Plerixafor (240μg/kg) and G-CSF (n=2), which was successful in all patients. These results demonstrate that the CTD induction regime results in a high rate of stem cell mobilization failures, which is associated with the requirement for an increased number of apheresis and re-mobilization procedures. The observations provide novel evidence that drugs with no previously demonstrated significant effect on stem cell mobilization can have a considerable negative impact on the stem cell yield when used in combination. The possible benefit of new drug combinations has to be balanced against the increase in cost, the potentially higher rate of complications, and delays or failures to progress to ASCT resulting from impaired stem cell mobilization. Disclosures:No relevant conflicts of interest to declare.