Addition Of Bortezemib To High Dose Melphalan Does Not Improve Response Rate Or Progression-Free Survival

Abstract The optimal induction regimen for patients with symptomatic myeloma who are eligible for transplantation is currently unknown. While thalidomide and dexamethasone is an effective regimen, it only has a 60 to 65% response rate and few complete responses (CR). Bortezomib based inductions have demonstrated a high response rate and an improved CR as well. Recently the IFM reported the initial results of the randomized bortezomib plus dexamethasone versus VAD induction followed by transplant, which demonstrated that fewer patients treated with bortezomib required tandem transplants. Wang et al reported a high induction response rate with the combination of BTD for only 2 cycles given over a 28 day cycle. Here we report our experience with the combination of BTD as induction therapy. 38 patients with symptomatic myeloma were treated with BTD as induction therapy. Patients received standard dose and schedule bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 with thalidomide at 100 mg/day, and 8 days of 40 mg dexamethasone every 21 days. The median age was 58 years (38–70) with 19 males. This was first line therapy for 29 patients, second line for 7 patients and 3rd line for 2. 12 patients had ISS stage 2 and 8 had ISS stage 3. The median β2M was 3.4 (1.66–41.89). Median creatinine was 1.1 (0.6–21.0). Nineteen patients had an IgG paraprotein, 6 an IgA, and 16 patients had light chain disease. The median number of cycles administered was 4 (2–8). Fifteen patients developed neuropathy of any grade. One patient developed grade 3 neuropathy. The overall response rate (CR, VGPR, plus PR) was 92%, with 58% of patients achieving a VGPR or better, and 21% of patients achieving an immunofixation negative CR. 1 patient had a minimal response and 2 patients had progressive disease (both patients presented with plasma cell leukemia). These two patients were treated with the combination of BTD with PACE chemotherapy. One of the two died from progressive disease and the other patient remains in complete remission after high dose therapy and autologous transplantation. 29 patients had consolidation therapy with high dose melphalan and autologous peripheral blood stem cell transplantation. Eight patients have collected stem cells without proceeding with immediate consolidation therapy. After a median follow up of 373 days, median progression free survival and overall survival have not been reached. One year overall survival is 97%. One year progression free survival is 87%. In conclusion, we report a very high response rate with a short course of bortezomib, thalidomide and dexamethasone with an acceptable toxicity profile. Follow up of patients in CR treated without high dose therapy and autologous transplant is in progress. Further studies of this active regimen are warranted.

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Abnormal Serum IgA Kappa / IgA Lambda Ratios at Maximum Response Predict Poor Progression Free Survival in Myeloma Patients.

Blood ◽

10.1182/blood.v114.22.4879.4879 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4879-4879 ◽

Cited By ~ 1

Author(s):

Heinz Ludwig ◽

Stephen Harding ◽

Caroline Bradley ◽

Dejan Milosavljevich ◽

Mark T Drayson ◽

...

Keyword(s):

Serum Proteins ◽

Progression Free Survival ◽

Maximum Response ◽

High Dose ◽

Free Survival ◽

Monoclonal Protein ◽

Clinical Assessments ◽

Stem Cell Rescue ◽

Site Group ◽

High Dose Melphalan

Abstract Abstract 4879 For some myeloma patients, co-migration of IgA monoclonal proteins with other proteins can make serum protein electrophoresis (SPE) densitometry inaccurate. Immunofixation (IFE) will identify the monoclonal immunoglobulins, however, it is not quantitative and requires skilful interpretation. Measurement of total IgA can also be used but has limited value when the monoclonal protein level is low. Antibodies which target the heavy and light chains of the immunoglobulin have now been developed, making it possible to quantify IgAk and IgA» in serum and to calculate the IgAk/IgA» ratio. Here we describe 2 patient groups where archived sera have been analysed to evaluate the utility of IgAk/IgA» ratios for monitoring response to treatment in myeloma patients. We also compared progression free survival (PFS) or overall survival (OS) for patients who did / did not achieve a normal IgAk/IgA» ratio at maximum response. Sequential, archived sera were analysed from 31 patients treated in the UK Myeloma VII trial (21 IgAk /10 IgA») and 27 patients treated at The Centre for Oncology and Haematology, Vienna (14 IgAκ /13 IgA»). Treatments utilised varied from combinations of cyclophosphamide, vincristine, doxorubicin and methylprednisolone with/without high-dose melphalan/stem cell rescue (UK) to VAD, Thalidomide-Dexamethasone, VMCP, DCEP with/without high dose melphalan/stem cell rescue (Vienna). Between 3 and 51 (median=6) sera were available for each patient. Serum IgAk and IgA» measurements were performed on a Siemens Dade-Behring BN™II nephelometer in UK and on a Roche Cobas Integra 800™ immunturbimeter in Vienna. IgAk/IgA» ratios were compared with a normal range derived from measurement of >100 blood donor sera. SPE and IFE were performed on a SEBIA Hydrasys™ electrophoresis system (UK) and on a SEBIA Kapillarys™ capillary electropheresis system and a Helena SPE 2000™(Vienna). IgAk/IgA» results were compared retrospectively to clinical assessment and outcome. Kaplan Meier curves and Cox regression analysis were performed using SPSS v14.0. For all 31 UK patients, changes in the IgAk/IgA» ratio were in accordance with the clinical assessments. With regard to the detection of residual disease, the IgAk/IgA» ratios remained abnormal beyond the time when SPE results had normalised and appeared approximately equal to IFE in sensitivity. The IgAk/IgA» ratio remained abnormal in all sera from the 13/31 patients who achieved a partial response (PR) or less. In 10/31 patients, SPE densitometry could not accurately quantify the monoclonal protein, either because there was no obvious monoclonal protein (5/10) or the monoclonal protein was obscured by other serum proteins (5/10). 18/31 patients achieved a complete response (CR) but 9/18 still had abnormal IgAk/IgA» ratios at this time and had a shorter progression free survival (PFS; 277 days v 912 days: p=0.01). Similarly, for the 27 Viennese patients, changes in the IgAκ/IgA» ratios were in accordance with overall clinical assessments. In 18/27 patients, where clinically determined maximum response was reached, an abnormal IgAk /IgA» was associated with a shorter overall survival (344 days v 2241 days: p=0.028). Monoclonal IgA proteins can be difficult to identify and measure using electrophoresis techniques because of their co-migration with other serum proteins. The results from this preliminary study indicate that the use of IgAk/IgA» ratios may offer an alternative technique for monitoring these myeloma patients. Furthermore, the IgAk/IgA» ratio may provide prognostic information at the point of maximum response. Disclosures Ludwig: Celgene: Honoraria; Mundipharma: Honoraria; AMGEN: Honoraria; Ortho-Biotech : Honoraria; Janssen-Cilag: Research Funding; Roche: Honoraria. Harding:The Binding Site Group Ltd: Employment. Bradwell:The Binding Site Group Ltd: Shareholder.

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Bortezomib-High Dose Melphalan Conditioning for the Treatment of MM Patients Undergoing ASCT

Blood ◽

10.1182/blood.v128.22.2273.2273 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2273-2273

Author(s):

Victor Jimenez-Zepeda ◽

Peter Duggan ◽

Paola Neri ◽

Ahsan Chaudhry ◽

Jason Tay ◽

...

Keyword(s):

Flow Cytometry ◽

Overall Survival ◽

Proteasome Inhibitor ◽

Research Funding ◽

Clinical Characteristics ◽

Conditioning Regimen ◽

Progression Free Survival ◽

High Dose ◽

Free Survival ◽

High Dose Melphalan

Abstract Introduction Recent data suggests that bortezomib, a proteasome inhibitor, in combination with high-dose melphalan (Bor-HDM) provides with a synergistic effect able to improve the level of response for MM patients undergoing auto-SCT. In the present study, patients receiving induction followed by ASCT with Bor-HDM and HDM alone were evaluated. Methods All consecutive patients undergoing ASCT from 01/2004 to 03/2016 were evaluated. All patients received induction chemotherapy before undergoing auto-SCT. Patients received conditioning with either HDM at 200 mg/m2 (or adjusted as per renal failure) or HDM with Bortezomib (Bor-HDM). Most of patients received Bortezomib conditioning at 1.3 mg/m2. As per physician discretion, the dose of 1 mg/m2 was also employed in 30% of cases. Definitions of response and progression were used according to the EBMT modified criteria. MRD negativity was assessed by flow cytometry at day-100 post-ASCT. Results Clinical characteristics are shown in Table 1. Among 301 cases, 129 were treated with Bor-HDM while 172 patients went onto receive HDM alone as part of the conditioning regimen. Induction regimens are shown in Table 1. At the time of analysis, 83% and 58% of patients in the Bor-HDM and HDM group are still alive and 34% and 69.1% of patients have already progressed, respectively. At day-100 post ASCT, ORR of 97%, with CR/VGPR rate of 84.2% was seen in the Bor-HDM group compared to 94.2% and 68.6% in the HDM group (p=0.001). MRD negativity was higher in the Bor-HDM group (33.3%) compared to HDM (12.2%) (p=0.001). Median OS was similar for Bor-HDM and HDM (p=0.864) (Fig 1a). In addition, median PFS did not differ among patients receiving HDM or Bor-HDM (37.7months vs 29.3 months, p=0.2) (Fig1b) In conclusion,Bor-HDMis a conditioning regimen able to provide higher rates ofnCR/CR, as well as MRD negativity compared to HDM alone. Further studies are warranted to explore this regimen, especially when other upfront therapies are employed. Overall Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Overall Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Figure 1 Progression-Free Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Figure 1. Progression-Free Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Disclosures Jimenez-Zepeda: Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene, Janssen, Amgen, Onyx: Honoraria. Neri:Celgene and Jannsen: Consultancy, Honoraria. Bahlis:Onyx: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria; BMS: Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau.

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Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232)

Blood ◽

10.1182/blood-2010-08-303487 ◽

2010 ◽

Vol 116 (26) ◽

pp. 5838-5841 ◽

Cited By ~ 134

Author(s):

Jeffrey A. Zonder ◽

John Crowley ◽

Mohamad A. Hussein ◽

Vanessa Bolejack ◽

Dennis F. Moore ◽

...

Keyword(s):

Response Rate ◽

Progression Free Survival ◽

Initial Therapy ◽

High Dose ◽

Oncology Group ◽

Free Survival ◽

Southwest Oncology Group ◽

High Dose Dexamethasone ◽

Grade 3 ◽

One Year

AbstractThe Southwest Oncology Group conducted a randomized trial comparing lenalidomide (LEN) plus dexamethasone (DEX; n = 97) to placebo (PLC) plus DEX (n = 95) in newly diagnosed myeloma. Three 35-day induction cycles applied DEX 40 mg/day on days 1 to 4, 9 to 12, and 17 to 20 together with LEN 25 mg/day for 28 days or PLC. Monthly maintenance used DEX 40 mg/day on days 1 to 4 and 15 to 18 along with LEN 25 mg/day for 21 days or PLC. Crossover from PLC-DEX to LEN-DEX was encouraged on progression. One-year progression-free survival, overall response rate, and very good partial response rate were superior with LEN-DEX (78% vs 52%, P = .002; 78% vs 48%, P < .001; 63% vs 16%, P < .001), whereas 1-year overall survival was similar (94% vs 88%; P = .25). Toxicities were more pronounced with LEN-DEX (neutropenia grade 3 or 4: 21% vs 5%, P < .001; thromboembolic events despite aspirin prophylaxis: 23.5% [initial LEN-DEX or crossover] vs 5%; P < .001). This trial was registered at www.clinicaltrials.gov as #NCT00064038.

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Interferon alfa-2a and interleukin-2 with or without cisplatin in metastatic melanoma: a randomized trial of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.7.2579 ◽

1997 ◽

Vol 15 (7) ◽

pp. 2579-2588 ◽

Cited By ~ 150

Author(s):

U Keilholz ◽

S H Goey ◽

C J Punt ◽

T M Proebstle ◽

R Salzmann ◽

...

Keyword(s):

Metastatic Melanoma ◽

Response Rate ◽

Interleukin 2 ◽

Progression Free Survival ◽

Interferon Alfa ◽

Survival Duration ◽

High Dose ◽

Free Survival ◽

Ifn Alpha ◽

Cytokine Treatment

PURPOSE The combination of interferon alfa-2a (IFN alpha) and high-dose interleukin-2 (IL-2) is active in metastatic melanoma. The addition of cisplatin (CDDP) has resulted in response rates greater than 50%. This study was performed to determine whether the addition of CDDP to a cytokine treatment regimen with IFN alpha and high-dose IL-2 influences survival of patients with metastatic melanoma. PATIENTS AND METHODS Patients with advanced metastatic melanoma were randomly assigned to receive treatment with IFN alpha 10 x 10(6) U/m2 subcutaneously on days 1 through 5 and a high-dose intravenous decrescendo regimen of IL-2 on days 3 through 8 (18 mIU/ m2/6 hours, 18 mIU/m2/12 hours, 18 mIU/m2/24 hours, and 4.5 mIU/m2/24 hours x 3) without (arm A) or with (arm B) CDDP 100 mg/m2 on day 1. Treatment cycles were repeated every 28 days to a maximum of four cycles. RESULTS One hundred thirty-eight patients with advanced metastatic melanoma, of whom 87% had visceral metastases, were accrued for the trial. Both regimens were feasible in a multicenter setting. The objective response rate was 18% without and 33% with CDDP (P = .04). The progression-free survival was 53 days without and 92 days with CDDP (P = .02, Wilcoxon; P = .09, log-rank). There was no statistically significant difference in survival between treatment arms, with a median overall survival duration for all patients of 9 months. CONCLUSION The addition of CDDP to cytokine treatment with IFN alpha and IL-2 does not influence survival of patients with advanced metastatic melanoma, despite a significant increase in response rate and progression-free survival.

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Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.9.3000 ◽

1998 ◽

Vol 16 (9) ◽

pp. 3000-3006 ◽

Cited By ~ 161

Author(s):

V Sandor ◽

V Stark-Vancs ◽

D Pearson ◽

R Nussenblat ◽

S M Whitcup ◽

...

Keyword(s):

Radiation Therapy ◽

Response Rate ◽

Survival Rates ◽

Primary Cns Lymphoma ◽

Progression Free Survival ◽

Complete Response ◽

Intraocular Lymphoma ◽

Cns Lymphoma ◽

High Dose ◽

Free Survival

PURPOSE Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone. PATIENTS AND METHODS Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity. RESULTS The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting. CONCLUSION The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival.

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Sorafenib may improve response rate and progression-free survival (PFS) duration in patients with iodine refractory thyroid cancer,

Inpharma Weekly ◽

10.2165/00128413-200816470-00024 ◽

2008 ◽

Vol &NA; (1647) ◽

pp. 6

Author(s):

&NA;

Keyword(s):

Thyroid Cancer ◽

Response Rate ◽

Progression Free Survival ◽

Improve Response Rate ◽

Free Survival

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Bortezomib and High Dose Melphalan (Bor-HDM) Compared to HDM Conditioning for the Treatment of Transplant Eligible Multiple Myeloma: Report from a Single Center

Blood ◽

10.1182/blood.v126.23.3189.3189 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3189-3189

Author(s):

Victor H Jimenez-Zepeda ◽

Peter Duggan ◽

Paola Neri ◽

Ahsan Chaudhry ◽

Marcia Culham ◽

...

Keyword(s):

Flow Cytometry ◽

Overall Survival ◽

Research Funding ◽

Clinical Characteristics ◽

Conditioning Regimen ◽

Progression Free Survival ◽

High Dose ◽

Free Survival ◽

High Dose Melphalan ◽

The Impact

Abstract Introduction Preclinical and clinical data suggest that bortezomib in combination with high-dose melphalan (Bor-HDM) provides with a synergistic effect able to improve the quality of response for MM patients undergoing auto-SCT. In the present study, we aimed to assess the impact of Bor-HDM conditioning on ORR, and MRD negativity for MM patients undergoing single auto-SCT at our Institution. Methods All consecutive patients who underwent single auto-SCT at Tom Baker Cancer Center (TBCC) from 01/2004 to 06/2015 using Bor-HDM or HDM as conditioning regimen were evaluated. Definitions of response and progression were used according to the EBMT modified criteria and a category of very good partial response (VGPR) was added. MRD negativity was assessed by multiparameter flow cytometry. All patients received induction chemotherapy before undergoing auto-SCT. Bortezomib was administered intravenously at 1-1.3 mg/m2 on days −5, −2, 1, and 4, while melphalan was given at 200 mg/m2 on day −1. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results Two-hundred and fifty-eight consecutive patients receiving Bor-HDM or HDM alone were evaluated. A total of 85 patients received Bor-HDM conditioning and 173 received HDM. Clinical characteristics and chemotherapy induction regimens are listed in Table 1. At day-100 post auto-SCT a ³VGPR was seen in 83.3% in the Bor-HDM group compared to 67.6% for HDM patients. The CR/nCR rate was higher in the Bor-HDM group (47.6% vs 23.6%) as well as MRD negativity assessed by flow cytometry (30.9% vs 9.7%, p=0.0001). Median OS in the Bor-HDM group was NR compared to 95 months for HDM alone (p=0.572), while median PFS was 39.3 months for Bor-HDM compared to 27 months for HDM (p=0.1). Median OS was shorter in the HR cytogenetic group regardless of the type of conditioning regimen employed (39 months vs NR for SR cytogenetics). In addition, patients who achieved MRD negativity, exhibited a longer OS (NR vs 78 months, p=0.007). Transplant-related mortality (TRM) was similar between both groups (p0.5). In conclusion, Bor-HDM is a safe and efficacious conditioning regimen able to increase the nCR/CR and MRD negativity rates compared to HDM. Further studies are warranted to explore this regimen, especially when other upfront therapies are employed, with special view on the high-risk MM patients where response rates are good but sustainability remains an issue. Table 1. Clinical Characteristics Characteristic Bor/HDM, N=85 HDM alone, N=173 Age (median) 58 59 GenderMaleFemale 51 (60%)34 (40%) 113 (65.3%)60 (34.7%) Hb (g/L) 112 117 Calcium (µmol/L) 2.25 2.29 Creatinine (µmol/L) 85 80 B2microglobulin (µmol/L) 3.3 2.79 Albumin (g/L) 31 35 Stage IStage IIStage III 154723 617333 M-spike (g/L) 34 30 LDH (IU/L) 194 180 BMPC (%) 40 33 Heavy chain:IgGIgAIgDFLC onlyBiclonalIgM 491811511 1142403210 Light chain:KappaLambdaBiclonal 50351 124471 High riskStandard risk 2263 36135 InductionCyBorDVDDexamethasoneRVD 4524016 16544315 Figure 1. Overall Survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 1. Overall Survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 2. Progression-Free survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 2. Progression-Free survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 3. Overall Survival for patients with MM undergoing single auto-SCT according to MRD negativity assessed by flow cytometry Figure 3. Overall Survival for patients with MM undergoing single auto-SCT according to MRD negativity assessed by flow cytometry Disclosures Jimenez-Zepeda: Celgene: Honoraria; J&J: Honoraria; Amgen: Honoraria. Duggan:Jansen: Honoraria; Celgene: Honoraria. Neri:Celgene: Research Funding. Bahlis:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Consultancy; Amgen: Consultancy; Johnson & Johnson: Research Funding.

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Thalidomide and Dexamethasone Induction Therapy Is Associated with Superior Progression-Free Survival after Autotransplant for Myeloma.

Blood ◽

10.1182/blood.v106.11.1171.1171 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1171-1171

Author(s):

Dan T. Vogl ◽

Selina Luger ◽

David L. Porter ◽

Elise A. Chong ◽

Stephen J. Schuster ◽

...

Keyword(s):

Stem Cell ◽

Induction Therapy ◽

Initial Treatment ◽

Progression Free Survival ◽

Initial Therapy ◽

High Dose ◽

Free Survival ◽

Autologous Transplant ◽

High Dose Melphalan

Abstract BACKGROUND: High-dose melphalan with autologous stem cell support improves survival when incorporated in the initial treatment of multiple myeloma. Published data show that induction thalidomide and dexamethasone (Thal/Dex) has a higher response rate than dexamethasone alone (Dex) or anthracycline induction (VAD or DVD), but the effect of initial induction therapy on outcomes after autologous transplant remains unclear. PATIENTS: We reviewed the records of 164 patients who received high-dose melphalan with autologous stem cell support as part of initial therapy for multiple myeloma at the University of Pennsylvania. Median age was 55 years (range 25 – 72). Durie-Salmon stage at diagnosis was II in 27% and III in 70% of patients. Induction regimens included VAD (62%), DVD (12%), Thal/Dex (11%), Dex (5%), and more than one regimen (10%). Post-transplant therapies for consolidation or maintenance included thalidomide (7%), interferon (23%), tandem autologous transplant (4%), non-myeloablative allogeneic transplant (7%), autologous co-stimulated T-cell infusion (14%), or observation until progression (45%). Patients who received Thal/Dex initial therapy were not significantly different than those receiving anthracycline-containing induction regimens (VAD/DVD), except for lower serum creatinine (median 0.9 vs 1.1 mg/dl; p=0.01), with a trend toward lower beta-2 microglobulin (B2M) and correspondingly lower ISS stage. RESULTS: Median overall follow-up is 29 months (range 7–120). Thal/Dex induction trended towards a higher Very Good Partial Response (VGPR) rate than anthracycline induction (29% vs 14%, p=NS) and a higher overall response rate (76% vs 68%, p=NS). All of the patients who received Thal/Dex as induction therapy are alive, with a median follow-up of 23 months (range 13 – 34), while overall survival in the anthracycline induction group is 85% at 2 years. Progression-free survival at 2 years is 93% for Thal/Dex induction and 58% for VAD/DVD (HR 0.12, p=0.039). The improvement in progression-free survival persists in Cox regression models that include creatinine and either B2M or ISS stage. CONCLUSION: In myeloma patients who undergo autologous stem cell transplant, thalidomide and dexamethasone induction may result in improved progression-free survival compared with VAD or DVD. Further studies of initial therapies for myeloma should assess long-term outcomes after autologous transplant. Progression Free Survival, By Initial Treatment Progression Free Survival, By Initial Treatment

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Interleukin-2 in the treatment of unresectable or metastatic renal cell cancer: a systematic review and practice guideline

Canadian Urological Association Journal ◽

10.5489/cuaj.34 ◽

2012 ◽

Vol 1 (1) ◽

Author(s):

Sebastien Hotte ◽

Tricia Waldron ◽

Christina Canil ◽

Eric Winquist

Keyword(s):

Systematic Review ◽

Renal Cell ◽

Response Rate ◽

Cell Cancer ◽

Interleukin 2 ◽

Progression Free Survival ◽

Mortality Data ◽

High Dose ◽

Eligibility Criteria ◽

Free Survival

Objective: We performed a systematic review of randomized controlled trials (RCTs) to assess the efficacy of interleukin-2 (IL-2) for the treatment of patientswith unresectable or metastatic renal cell carcinoma (RCC).Methods: We searched the literature to identify RCTs or meta-analyses of RCTscomparing treatment regimens with IL-2 to those without. Outcomes of interestincluded overall or progression-free survival, response rate, toxicity andquality of life.Results: We identified 36 RCTs, and 6 met the eligibility criteria (1098 patients).We studied IL-2 alone and in combination with other agents, including interferon-alpha (IFN-a), 5-fluorouracil (5-FU), and 13-cis-retinoic acid or tamoxifen.No trials comparing high-dose IL-2 to non-IL-2 regimens were identified.A meta-analysis of 1-year mortality data from the 6 trials did not show a differencebetween IL-2-based regimens and non-IL-2 controls. Two of the 6trials detected statistically significant longer survival with IL-2 combinedwith IFN-a and 5-FU. Of the 4 trials that assessed progression-free survival, 3 reported significantly longer progression-free intervals with IL-2-based regimens.Five trials reported response rates; pooling the rates from these trialsgave an overall weighted response rate of 13.3% (range 9%–39%) and 5.3%(range 0%–20%) for IL-2-containing regimens and non-IL-2 regimens, respectively.IL-2-based regimens were more toxic than were non-IL-2 controls;the most frequently reported grade 3–4 toxicities were hypotension (range6%–68%), fever (2%–56%), nausea or vomiting or both (6%–34%), diarrhea(1%–28%) and cardiac toxicity (11%–25%). None of the trials reported healthrelatedquality-of-life data.Conclusion: Non-high-dose IL-2 containing regimens do not provide superiortreatment efficacy over non-IL-2-based regimens, with added toxicity, and thereforeshould not be used as standard treatment for patients with unresectableor metastatic RCC. High-dose IL-2 should only be used by experienced physiciansin the context of a clinical trial or investigative setting.

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