Combination Of Prednisone Research Articles

Myeloma Therapy: 25 Years Forward—Immune Modulation Then and Now

Myeloma Therapy: 25 Years Forward—Immune Modulation Then and Now

Direct hospital resource utilization and costs of treating patients with multiple myeloma in Southwest Sweden: A 5-year retrospective analysis

Background: Approximately 570 patients are diagnosed with multiple myeloma (MM) in Sweden each year. Few studies have estimated the cost of treatment for these patients. Objective: The purpose of this study was to retrospectively investigate the direct hospital resource utilization and costs associated with the treatment of patients with MM in southwest Sweden. Methods: Patients aged ≥18 years who initiated first-line chemotherapy in the year 2001 at hospitals in southwestern Sweden were included in this retrospective chart review. Direct hospital-based resources and their corresponding costs (year-2006 euros) for each patient were calculated until the patient's death, or until December 31, 2005. Costs for outpatient and terminal stage care related to MM were not included. Results: Ninety-four patients were included; 20 were still alive at study completion. Mean age at diagnosis was 76 years and patients were followed for a mean of 32.7 months; 55% were males and 74% had at least 1 comorbidity. First-, second-, and third-line treatment lasted a mean of 24.3, 5.8, and 2.6 months, and included 2.8, 2.6, and 3.1 chemotherapy drugs per patient, respectively. Of the 80 patients who received first-line chemotherapy, 72 were prescribed melphalan and 55 patients received a combination of melphalan and prednisone, as recommended by Swedish treatment guidelines. The mean total cost per patient was €88,199, or €2770 per patient-month. Therapy-induced and comorbidity-related events constituted 42% of total costs, as much as autologous stem-cell transplantation and inpatient care together. Chemotherapy, bisphosphonate, and blood cell-enhancement drugs each amounted to only 2% of total costs, but chemotherapy drugs increased from €29/month in first-line therapy to €453/month in third-line therapy. Conclusions: The cost of treating Swedish patients with MM varied greatly between individuals but, overall, chemotherapy drugs constituted only a minor part of the total monthly cost (2%), whereas costs for inpatient stays and therapy-induced adverse events or comorbidity-related events accounted for 35% and42%, respectively. There was no significant differencein monthly cost between treatment lines.

EBV-positive immunodeficiency lymphoma after alemtuzumab-CHOP therapy for peripheral T-cell lymphoma

AbstractChemotherapy with alemtuzumab and the combination of cyclophosphamide, adriamycin, oncovin, and prednisone (CHOP) has become experimental trial therapy for aggressive T-cell lymphoma. Several multicenter phase 3 trials will incorporate this scheme. As part of an ongoing phase 2 trial in which we recently treated 20 patients with 8 cycles of CHOP every 2 weeks with 3 additional doses of 30 mg alemtuzumab per cycle, we observed the development of Epstein-Barr virus (EBV)-positive lymphoproliferative disease, after completion of the immunochemotherapy in 3 patients with peripheral T-cell lymphoma. Because the occurrence of EBV-positive lymphoproliferative disease is rare after alemtuzumab monotherapy, such as is given for chronic lymphocytic leukemia, we think that early reporting of this potential side effect is warranted. It may be caused by intrinsic T-cell defects in patients with T-cell lymphoma, or by the combination of alemtuzumab with CHOP chemotherapy.

Randomized comparison of cladribine alone or in combination with cyclophosphamide, and cyclophosphamide, vincristine and prednisone in previously untreated low‐grade B‐cell non‐Hodgkin lymphoma patients

The objective of this study was to compare the efficacy of 3 regimens, cladribine alone, cladribine and cyclophosphamide combination, or cyclophosphamide, vincristine, and prednisone combination in previously untreated patients with low-grade B-cell non-Hodgkin lymphoma (LGNHL). For this 3-arm, phase 3 study, 197 patients were randomly allocated to receive 6 monthly courses of cladribine alone, cladribine and cyclophosphamide combination, or cyclophosphamide, vincristine, and prednisone combination. Patients for whom all clinical data were available and 162 patients who completed scheduled chemotherapy were analyzed for the endpoints of this study. Compared with cyclophosphamide, vincristine, and prednisone combination regimen, cladribine alone or cladribine and cyclophosphamide combination induced higher probability of overall response (odds ratio [OR] = 4.0; 95% confidence interval [CI], 1.7-9,3; P = .002, and OR = 8.5; 95% CI, 3.2-22.7; P < .0001, respectively), complete remission (OR = 5.8; 95% CI, 1.8-18.5; P = .003; and OR = 14; 95% CI, 4.4-44; P < .0001, respectively), progression-free survival (log-rank test P < .0001), but not overall survival. After incorporating the International Prognostic Index in multivariate analysis, treatment with cladribine-containing regimens remained an independent prognostic factor for progression-free survival (chi(2) = 35.94; hazard ratio = 2.38; P < .0002). Incidences of infections were similar in the randomized groups, whereas cladribine and cyclophosphamide combination, but not cladribine alone, induced more frequent neutropenia, anemia, and thrombocytopenia compared with cyclophosphamide, vincristine, and prednisone combination (P < .05 for each). This resulted in a higher frequency of prolongation of intervals between cladribine and cyclophosphamide combination and cyclophosphamide, vincristine, and prednisone combination cycles (P < .05), but dose reductions due to hematological or other toxicity did not differ significantly in cladribine alone, cladribine and cyclophosphamide combination, and cyclophosphamide, vincristine, and prednisone combination groups. For patients with LGNHL, first-line cladribine alone or cladribine and cyclophosphamide combination regimens both provided similar treatment responses, acceptable toxicity, and better response rates than cyclophosphamide, vincristine, and prednisone combination.

Tacrolimus for Myasthenia Gravis

Tacrolimus is a macrolide T cell immunomodulator that is used in myasthenia gravis (MG) patients to affect muscle contraction (ryanodine receptor by modulating intracellular calcium-release channels and increasing muscular strength), glucocorticoid receptors (increasing intracellular concentration of steroids and blocking the steroid export mechanism), and an increase in T cell apoptosis. In this study, we report the results of low-dose tacrolimus (0.1 mg/kg/day) treatment in 212 MG patients. There were 110 thymectomized, cyclosporine- and prednisone-dependent patients; 68 thymectomized patients who started tacrolimus early postoperatively (24 h after operation); and 34 patients over 60 years old with nonthymomatous generalized MG or in whom thymectomy was contraindicated. The mean follow-up time was 49.3 +/- 18.1 months. Muscular strength showed an increase of 23% after 1 month of treatment and 29% at the end of the study. The acetylcholine receptor antibodies decreased significantly from a mean of 33.5 nmol/L at base line to 7.8 nmol/L at the final visit. In the thymectomy group with combined prednisone and tacrolimus stratified by histology of the thymus, the mean probability to attain complete stable remission at 5 years was 80.8% in patients with hyperplasia, 48.1% in thymic involution, and 9.3% in patients with thymoma. In 4.9% of patients, tacrolimus was withdrawn because of major adverse effects. Our results suggest that a low dose of tacrolimus is effective for MG and could be included to the armamentarium for this autoimmune disease. The present results should be interpreted considering the limitations of a retrospective clinical study. Confirmation of these results in randomized studies is desirable.

Docetaxel (D) plus prednisone (P) in combination with metronomic cyclophosphamide (CTX) and celecoxib (C) as first line chemotherapy in metastatic hormone refractory prostate cancer (HRPC): Phase II clinical trial with pharmacodynamic evaluation

16084 Background: Docetaxel based chemotherapy has became the standard of care for metastatic HRPC, moreover, low-dose metronomic antiangiogenic CTX and C have demonstrated a significant activity in preclinical and clinical studies without relevant toxicities. Combination of such strategies could be of interest in prostate cancer patients. Methods: A total of 19 patients with metastatic HRPC received D 60 mg/sqm iv day 1 every 3 weeks up to 12 cycles and from day 2 in a continuous fashion: P 5 mg po BID, CTX 50 mg po daily and C 200 mg po BID. Primary end point was PFS; secondary were: activity (PSA reduction >50%); objective responses, toxicities (NCI-CTC criteria), OS, evaluation of plasma levels of thrombospondin-1 (TSP-1), VEGF, sVEGFR-2, VE-cadherin mRNA; expression and synthesis of TSP-1 and VEGF in peripheral blood mononuclear cells. Patients (pts) characteristics: median age 69,5 years (59–78), median PS 1 (0–2), median baseline PSA 48,3 ng/ml (10–444); main sites of disease: bone 17 pts (90%), lymphnodes 1 pt (5%), liver 1 pt (5%). Results: 14 pts were evaluable for toxicity and response. Median number of docetaxel cycles administered was 8,5 (1–12) and median duration of metronomic CTX plus P and C was 183 days (18–636 days). Overall PSA decrease ≥ 50% was found in 11 pts (78%), with 6 patients that achieved a PSA complete response (43%). Three pts showed stable disease (21%). Up today, only 4 pts (28%) experienced disease progression. Median time to PSA progression was 7,7 months (3,7–10,3 months). Main grade 3 hematologic or non-hematologic toxicities were: neutropenia (1 pt; 5%) and diarrhoea (1 pt, 5%). No grade 4 toxicities have been observed. Conclusions: combination of docetaxel plus metronomic chemotherapy with CTX and C was feasible and showed only mild toxicity, preliminary activity was also interesting. The evaluation of biologic and pharmacodynamic effects of the combination is ongoing. No significant financial relationships to disclose.

PROGNOSIS OF ACQUIRED HEMOPHILIA IN OLDER PEOPLE

PROGNOSIS OF ACQUIRED HEMOPHILIA IN OLDER PEOPLE

Treatment of myeloma in the elderly

The treatment of elderly patients with multiple myeloma was based for the last forty years on the combination of alkeran plus prednisone. The survival was short. Three new molecules, thalidomide, bortezomib and revlimid are completely changing the way we treat myeloma as well as the prognosis. These new molecules are tested either alone or in combination. The addition of thalidomide to alkeran plus prednisone has increased overall survival of two years. For the first time, major therapeutic improvements are emerging giving rise to better prognosis.

Acquired hemophilia: a case report

Acquired hemophilia is a severe bleeding diathesis that affects both males and females. It is caused by suddenly appearing autoantibodies that interfere with coagulation factor VIII activity. This disorder is characterized by spontaneous and post-traumatic subcutaneous bleeds and massive mucosal hemorrhages. We report in the current article a case of acute renal failure and bleeding from the urinary tract caused by idiopathic acquired hemophilia in a 54-year-old woman. Hemostatic tests indicated prolonged activated partial thromboplastin time (APTT) to 107.8 sec (norm 26-36 sec), normal value of the prothrombin index which was 82% (norm 70-130%), increased fibrinogen concentration to 583 mg/dl (normal value 200-400 mg/dl), the bleeding time was 5 min and 20 s (norm < 10 min) and the platelet count was 366 x 10(9)/l (norm 130-400 x10(9)/l). The autoantibody against factor VIII in a titer of 121 Bethesda Units/ml (BU/ml) and decreased factor VIII activity to 2% (norm 50-150%) with normal plasma concentration of factor IX. Activated (FEIBA, Baxter) and nonactivated prothrombin complex concentrates (factor IX concentrate) have been used in the treatment of bleeding episode. Immunosuppressive treatment with the combination of oral prednisone 60 mg/24h and cyclophosphamide 150 mg/24h was administered in order to remove the factor VIII inhibitor. Reduction of the factor VIII inhibitor titer to 38 BU/ml and increase of factor VIII activity to 4% was initially achieved. This treatment has been continued for two years and led to normalization of hemostatic parameters (APTT 26 sec, factor VIII activity 108%) which means a total removal of factor VIII inhibitor.

Klinik und Therapie des anaplastischen T-Zonen-Lymphoms

Between 1 January 1975 and 30 June 1983 four anaplastic T-cell lymphomas (1.1%) were observed among 368 non-Hodgkin lymphomas. The median age was 61.5 years (range 33 and 76 years). Males and females were equally affected. At the time of diagnosis stage IIIM- was seen in three cases and stage IVM+ in one case. In three of the four patients a marked B-symptomatology was noted. The median Karnofsky index was below 50%. Due to cardiac failure two patients were treated with combined cyclophosphamide, vincristine, procarbazine and prednisone and a lasting complete remission was achieved in both cases. The two other patients were treated with combined bleomycin, adriamycin, cyclophosphamide, vincristine and prednisone due to rapid progression. Lasting complete remissions were seen in the same manner. The median survival time is 42+ months, the Karnofsky index 100%.

Hypertension After Pediatric Heart Transplantation is Primarily Associated With Immunosuppressive Regimen

Hypertension is recognized as prevalent in pediatric cardiac transplant recipients. This study investigated risk factors for this complication and, in particular, the role of immunosuppression. Results of 24-hour ambulatory blood pressure monitoring of children surviving more than 1 year after cardiac transplantation were analyzed retrospectively. Subjects were designated either hypertensive or normotensive by comparison with published normal values. To identify factors associated with hypertension, clinical data contemporaneous with 24-hour ambulatory blood pressure monitoring were collected and compared between the groups. In the 51 children studied, the incidence of hypertension was 49%. Hypertensive and normotensive recipients were similar for sex, age at transplantation, time between transplantation and 24-hour ambulatory blood pressure results, and choice of calcineurin inhibitor. In contrast, hypertensive patients were taking significantly more immunosuppressive agents (2.92 vs 2.12 p < 0.01), had higher tacrolimus levels (10 vs 8.1 microg/liter, p = 0.03), and were more likely to be on maintenance prednisone therapy (64% vs 23%, p < 0.01) or regimens including sirolimus (40% vs 12%, p = 0.03). Multiple regression analysis controlling for tacrolimus level showed a combination of prednisone and sirolimus was more strongly associated with hypertension than either agent alone, with an odds ratio of 7.3 (95% confidence interval, 1.5-36.1) vs 4.1 (95% confidence interval, 0.85-26.3). Hypertension after pediatric cardiac transplantation is a common problem and primarily associated with immunosuppressive regimen.

The addition of rituximab to CHOP chemotherapy improves overall and failure-free survival for follicular grade 3 lymphoma

BackgroundThe benefit of adding rituximab to anthracycline-based therapy for follicular lymphoma grade 3 has not been studied. Patients and methodsWe retrospectively reviewed the records of 45 patients with follicular grade 3 lymphoma who were treated with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) at The University of Texas MD Anderson Cancer Center. Response rate, failure-free survival (FFS), and overall survival (OS) were estimated and a historical comparison to CHOP-only-treated patients was made. ResultsThe International Prognostic Index (IPI) distribution was 47% low, 36% low intermediate, 13% high intermediate, and 4% high risk. The complete response rate was 96%. Forty-four of 45 patients are still alive. Median follow-up for the alive patients is 3.5 years. The 3-year FFS rate according to the IPI was 80% [95% confidence interval (CI) 64% to 100%] in low, 81% in low intermediate (95% CI 64% to 100%), and 50% (95% CI 25% to 100%) in high-intermediate/high-risk patient group. The addition of rituximab to CHOP improved both 5-year FFS, 71% (95% CI 58% to 87%) compared with 44% (95% CI 36% to 55%) with P value of 0.019, and 5-year OS, 98% (95% CI 93% to 100%) compared with 75% (95% CI 67% to 84%) with P value of 0.0034. ConclusionThe addition of rituximab to CHOP provided a high response rate and excellent early survival. Poor-risk patients continue to demonstrate a high rate of failure despite the use of rituximab.

Clinical Features, Differential Diagnosis and Treatment of Autoimmune Hepatitis in the Elderly

Autoimmune hepatitis affects all ages, and it is probably under-diagnosed in the elderly. Patients aged >or= 60 years have a higher frequency of cirrhosis at presentation than adults aged <or= 30 years, and they more commonly have HLA DRB1*04. These findings suggest that host factors affect the clinical phenotype by influencing the antigens that are presented to immunocytes and the nature of the immune response. The elderly may have an indolent progressive disease that is asymptomatic or masked by other concurrent rheumatic conditions. An acute, even fulminant, presentation may reflect de novo disease or a spontaneous exacerbation of a pre-existent chronic process. Centrilobular (zone 3) necrosis may reflect an early histological stage that transforms later to classical interface hepatitis. Diagnostic criteria have been codified, and a scoring system allows systemic assessment of all clinical features and quantifies the strength of the diagnosis. Prednisone in combination with azathioprine is the safest effective initial treatment, and all elderly patients with severe disease should be treated vigorously to full resolution of clinical, laboratory and histological features. Adverse effects of treatment occur mainly with protracted treatment (>18 months) and repeated therapies after relapse. Adjustments in the management strategy are warranted for an incomplete response or a need for re-treatment after relapse. Azathioprine (2 mg/kg/day) should be used as a corticosteroid-sparing, long-term maintenance therapy in these instances. Treatment failure is uncommon in the elderly, and age-related changes in the cellular immune response may attenuate the disease and enhance its response to therapy. Concurrent adjuvant therapies must focus on maintenance of bone density.

Sympathetic Ophthalmia Following Vitrectomy for Endophthalmitis After Intravitreal Bevacizumab

Purpose: To describe a case of sympathetic ophthalmia following vitrectomy for endophthalmitis after an intravitreal injection of bevacizumab. Design: Retrospective case report. Methods: An 84-year-old male developed sympathetic ophthalmia 4 months after vitrectomy for endophthalmitis following an intravitreal injection. The inciting blind eye was enucleated. Results: Histopathology demonstrated sympathetic ophthalmia and phacoanaphylactic endophthalmitis. Visual acuity improved from 20/200 to 20/30 in the sympathizing eye with a combination of oral prednisone and azathioprine. Conclusions: Sympathetic ophthalmia can develop following exogenous endophthalmitis but has a good visual prognosis with appropriate treatment.

The Role of Angiogenesis Inhibitors in Prostate Cancer

Prostate cancer is the leading noncutaneous malignancy in American men. Only the combination of docetaxel and prednisone has been shown to improve survival in patients with metastatic castrate-resistant prostate cancer. However, responses are short and a search for better agents either alone or synergistic with chemotherapy continues to be an urgent medical need. Angiogenesis has been shown to be a prerequisite event for tumor growth and metastasis in prostate cancer. Several strategies have been used to target angiogenesis in prostate cancer. These include blocking of pro-angiogenic factors via monoclonal antibodies or small molecule inhibitors targeting downstream signaling effector pathways, direct inhibition of endothelial cells, or targeting other receptors involved in cell adhesion, proliferation, and survival. Agents such as thalidomide and bevacizumab have shown encouraging results in phase II trials, and this review focuses on the clinical trials that have used these agents and other novel agents. The use of angiogenesis inhibitors is rapidly emerging as a promising treatment strategy in a variety of solid tumors, currently including prostate cancer.

Sustained ventricular tachycardia in a thalidomide-treated patient with primary plasma-cell leukemia

A 68-year-old man diagnosed with primary plasma-cell leukemia was given thalidomide maintenance treatment for his disease. He had previously failed induction therapy with cyclophosphamide, vincristine, adriamycin, and dexamethasone, but achieved complete remission after melphalan therapy. Multiple syncopal episodes started to occur during thalidomide treatment, and a Holter electrocardiogram showed multiple abnormalities, with an episode of sustained ventricular tachycardia. Blood tests, peripheral blood smear, bone-marrow biopsy and aspirate, Holter electrocardiogram. Sustained ventricular tachycardia possibly owing to thalidomide treatment. Thalidomide withdrawal, dexamethasone maintenance therapy, monthly oral courses of combined melphalan and prednisone, salvage therapy with bortezomib.

Phase II Study of Lenalidomide and Prednisone for Patients with Myelofibrosis.

Prompted by the activity of lenalidomide (Revlimid®) in pts with chronic idiopathic myelofibrosis (CIMF), we sought to evaluate the safety and efficacy of the combination of lenalidomide and prednisone in a phase II study for pts with CIMF. The rationale for this combination is that the anti-angiogenic and anti-TNFa effects of lenalidomide may be potentiated by the effects of prednisone to reduce marrow fibrosis and improve hematopoiesis in CIMF. Initial therapy consisted of lenalidomide 10 mg/d (dose level [DL] 0) on days 1–21 of a 28–day cycle for 6 cycles, in combination with prednisone 30 mg/d orally during cycle 1, 15 mg/d orally during cycle 2, and 15 mg/d every other day during cycle 3. The lenalidomide dose could be reduced to 5 mg/d (DL -1) or to 5 mg/d every other day (DL -2), or increased to 15 mg/d (DL +1) or 20 mg/d (DL +2) depending upon toxicity or lack of response, respectively. A total of 40 pts (23 male, 17 female) have been enrolled. The median age was 62 years (range, 41–86), time from CIMF diagnosis to the study treatment 10 months (range, 0–269), WBC count 87x109/L (range, 1.1–89), hemoglobin 9.8 g/dL (range, 7.8–17.3), platelets 137x109/L (range, 8–1183). Pts had received a median of 1 prior therapy (range 0–4): hydroxyurea (HU; n=14), anagrelide (AG; n=4), azacitidine (n=6), steroids (n=5), thalidomide (n=4), and interferon (n=3). Ten (25%) pts had not received any prior therapy. JAK2 V617F mutation was detected in 18 (50%) of 36 tested pts and 20 (50%) of 40 had abnormal cytogenetics. A total of 260 cycles have been administered. All 40 pts are evaluable for response and toxicity. Responses have been observed in 12 (30%) pts, including complete response (CR) in 2 (normal blood counts and <5% bone marrow blasts, off HU, AG, growth factors, and no transfusions); partial response (PR) in 7 (at least 2 of the following: Hb increase by ≥2 g/dL, 50% increase in platelets, decrease of bone marrow blasts or organomegaly by ≥50%, normalization of WBC count without blasts, or reduction in bone marrow fibrosis; off HU, AG, growth factors, and transfusion independence); and hematologic improvement (HI) in 3 (at least 2 of the following: decrease by ≥25% of pretreatment leukocytosis, splenomegaly, or marrow blasts, or increase of Hb by ≥1g/dl without growth factor or transfusion support or platelets by ≥25%; off HU, AG, growth factors). Median time to response was 12 weeks (range, 2–32). Responses have been sustained for a median of 15 wks (range, 5–36) and are ongoing in all 12 responders. Overall, 21 (53%) pts experienced grade 3–4 toxicity, being the most frequent neutropenia, anemia, musculoskeletal pain, and fatigue. Twenty-four (60%) pts have required dose reduction to DL -1, of which 5 (12.5%) further reduced to DL -2. One (2.5%) pt dose-escalated to DL +1, while 15 (25%) remained at DL 0. Twenty-one (53%) pts discontinued lenalidomide due to: lack of response (n=8), pt's decision (n=7), grade 3–4 toxicity (n=5), and poor compliance (n=1). No deaths or transformation to acute myeloid leukemia occurred. In summary, the combination of lenalidomide and prednisone is an active and generally well-tolerated regimen for pts with CIMF. Longer follow-up is warranted to evaluate the durability of ongoing responses. Updated results will be presented at the meeting.

Bortezomib in Combination with Bendamustine and Prednisone in the Treatment of Patients with Refractory/Relapsed Multiple Myeloma.

Introduction: Bortezomib is a novel proteasome inhibitor that has shown important clinical efficacy either as a single agent or in combination with other cytostatic agents in relapsed/refractory multiple myeloma (MM). The combinated treatment of bortezomib with bendamustine and prednisone (BPV) was assessed to determine the efficacy and toxicity of this regiment in patients with advanced MM.Methods: Between January 2005 and July 2007, 46 patients (median age 63; range 31–77 years) with relapsed or refractory MM (29 patients stage III a, 17 patients III b) were treated with bendamustine 60 (−80) mg/qm on day 1 and 2, bortezomib 1,3 mg/qm on day 1, 4, 8 and 11, and prednisone 100 mg on day 1, 2, 4, 8 and 11. Cycles were repeated every 21 days until maximum response or progressive disease. The time from first diagnosis ranged from 1 to 183 (median 36) months. The duration of the last remission before beginning the BPV-therapy was 6 (range 0–36) months. Previous therapy lines (median 2, range 1–6) included 18 × thalidomide, 10 × autologous PBSCT, and 9 × autologous/allogeneic PBSCT. 16 patients were refractory to the last treatment. 22 patients had preexistent severe thrombocytopenia, leukocytopenia or anemia (WHO grade 3 or 4). Response was assessed using EBMT criteria modified to include near complete remission (nCR) and very good partial remission (VGPR).Results: 36 patients (78%) responded after at least one cycle of chemotherapy with 2 CR, 5 nCR, 6 VGPR, 15 PR and 8 MR. 4 patients had stable disease and 6 patients had a progress. With a median follow up of 13 months, EFS, and OS at twelve months for patients without severe haematological toxicities due to previous treatments (n=24) were 46% and 79%, respectively. Outcome for these patients was significantly better compared to patients with severe haematological toxicities (grade 3 or 4, n=22) where EFS, and OS were 10% and 22%, respectively (p<0,01). The median number of the BPV-treatment was 2 (1–7) cycles. 20 of 36 responding patients showed a rapid decrease of the myeloma protein and reached the best response after the first cycle and 12 after the second cycle. The regimen was well-tolerated with few significant side effects reported. New cytopenias occured infrequently (four patients had a thrombocytopenia grade 3, and two patients had a grade 4 thrombocytopenia). 1 patient had a moderate new polyneuropathy (grade 2).Summary: These results indicate that the combination of bortezomib, bendamustine and prednisone is effective and well tolerated in a heavily pretreated population of patients with relapsed or refractory MM.

The Addition of Rituximab to CHOP Chemotherapy Improves Response Rate, Failure-Free Survival and Overall Survival for Follicular Grade 3 Lymphoma Compared to CHOP Alone

Background: FL3 is a subcategory of follicular lymphomas that is challenging in that it behaves aggressively like large cell lymphomas. If treated with CHOP, however it has a clinical course of relapse and treatment failure similar to grade 1–2 follicular lymphoma. We looked at the outcome of FL3 patients treated with RCHOP, combining rituximab with CHOP. There are no large study reports of this regimen's results in FL3 to our knowledge.Patients and Methods: We retrospectively reviewed the records of 45 patients with follicular grade 3 lymphoma who were treated with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) at The University of Texas MD Anderson Cancer Center (UTMDACC). Response rate (RR), failure-free survival (FFS), and overall survival (OS) were estimated and a historical comparison to 111 CHOP only treated patients was made.Results: The International Prognostic Index (IPI) distribution was: 47% Low, 36% Low-Intermediate, 13% High-intermediate, and 4% High-risk. The complete response rate was 96%. Forty-four out of 45 patients are still alive. Median follow-up is 3.5 years. The 3-year FFS rate according to IPI was 80% (95% CI: 64% to 100%) in low risk, 81% in low-intermediate (95% CI 64% to 100%), and was 50% (95% CI: 25% to 100%) in high-intermediate/high-risk patient group. The addition of rituximab to CHOP improved both 5-year FFS, 71% (95% CI: 58% to 87%) compared to 44% of CHOP alone (95% CI: 36% to 55%) with p-value of 0.019 and 5-year OS, 98% (95% CI: 93% to 100%) compared to 75% (95% CI: 67% to 84) with p-valule of 0.0034. The addition of rituximab to CHOP improve the FFS compared to CHOP alone when subgroups of IPI were analyzed and compared (p=.002)Conclusion: The addition of rituximab to CHOP provided a high response rate and excellent early survival. Poor risk patients continue to demonstrate a high rate of failure despite the use of rituximab.

A Phase II Trial of Myeloma Induction Therapy with Cyclophosphamide, Bortezomib, and Dexamethasone (Cybor-D): Improved Response over Historical Lenalidomide-Dexamethasone Controls.

Background: We previously reported an 85% response rate with 54% CR/nCR using a combination of cyclophosphamide (Cy), prednisone, and bortezomib (BZ) in relapsed myeloma (MM). We now report a Phase II clinical trial using a combination of Cy, BZ, and dexamethasone (Dex) [Cybor-D] in newly-diagnosed MM. We then compare the activity of this combination with historical controls treated with our current induction standard of Lenalidomide-Dexamethasone (L-Dex).Methods: 30 patients have been enrolled on Cybor-D. Treatment consists of Cy 300mg/m2 p.o. days 1, 8, 15, and 22; BZ 1.3 mg/m2 days 1, 4, 8, and 11, and Dex 40mg p.o. days 1–4, 9–12, 17–20. Prophylactic use of acyclovir, a quinolone and antifungal prophylaxis was highly recommended for all patients on study. Growth factors were allowed. As a relevant contemporaneous control for speed and depth of response, we used 33 patients treated on a recent Mayo Clinic trial of L-Dex (Rajkumar. Blood: 2005 106;4050–3). Response was defined according to IMWG criteria although in the current trial, bone marrows for confirmation of CR are not yet available on all patients.Results: At time of current analysis, 17 patients on Cybor-D were evaluable through at least one cycle for response and toxicity. Baseline characteristics included mean age of 57, 29% female, 41/24% ISS stage II/III. There were statistically more early stage patients on L-Dex; otherwise, baseline patient characteristics were similar. The mean % decline in monoclonal (M) protein from baseline following cycles 1–4 of Cybor-D were 71%, 90%, 93%, 96%. This compares favorably with L-Dex where equivalent % decline in M proteins were 66%, 77%, 80%, and 79%. Thus, in preliminary results, Cybor-D produces a more rapid initial decline and mean % reduction in M protein than L-Dex. Overall response rate (≥ PR) after one cycle of Cybor-D was 77% with 36% obtaining ≥VGPR (L-Dex 73% and 18% respectively). The % of patients obtaining ≥VGPR after each cycle was 36%, 64%, 77%, and 100% for Cybor-D as compared to 18%, 36%, 42%, and 33% for L-Dex. The overall ≥VGPR at the end of four cycles of Cybor-D is currently100% (≥ 66%nCR using older nomeclature). Major toxicities ≥ grade 3 for Cybor-D included hematologic (37%), hyperglycemia (15%) and neuropathy (11%).Conclusions: In summary, for newly-diagnosed MM patients, four cycles of Cybor-D produces more frequent, rapid and deep responses when contrasted with historical L-Dex controls. Further confirmation of response rates and effect on TTP will be required.