High response rate to low-dose rituximab plus high-dose dexamethasone as frontline therapy in adult patients with primary immune thrombocytopenia

Abstract Abstract 3332 Introduction Corticosteroids are the initial standard therapy for primary immune thrombocytopenia (ITP). A short course of high-dose dexamethasone as initial therapy is an alternative to prednisone with high initial responses, but about half of the patients relapse. Low dose rituximab has been used in the treatment of relapsed ITP, showing a similar activity to the standard dose. The aim of this prospective study was to evaluate the efficacy, safety and response duration of low-dose rituximab plus short pulses of high-dose dexamethasone as front-line therapy in newly diagnosed ITP adults. Methods Patients ≥18 years old with newly diagnosed received dexamethasone, 40 mg/day/i.v. for 4 consecutive days (+1, +2, +3, +4), rituximab was administered at a fixed dose of 100 mg as an i.v. infusion weekly for 4 consecutive doses (days +1, +8+, +15 and +22). The use of rescue therapy was allowed, using the same schedule of dexamethasone, before day 30, but only if the platelet count was < 20×109/L. A complete blood cell count was performed at enrollment, weekly for the first 28 days, monthly until month 6 and then every 3 months. The degree of response was defined as follows: a complete response (CR) was a platelet count ≥ 100 × 109/L; a complete sustained response (CSR) was considered if it was maintained for six months. Partial response (PR) was defined as a platelet level between 50 and 100 × 109/L; an overall response (OR) was defined as partial or complete response. Patients with a platelet count <30 × 109/L were considered non-responders (NR). Time-to-response (TTR) and time-to-complete response (TCR) were also assessed, as well as the safety profile and side effects incidence according to the National Cancer Institute Common Toxicity Criteria version 3.0. Results Twenty-one consecutive patients were enrolled from December 2009 to December 2011 (17 women and 4 men); median age was 51 years (range, 18–82). The median platelet count at baseline was 5.19 × 109/L (range, 0.3–24.2 × 109/L). Patients were followed for a median of 12 months (range, 1–25). At day +28, sixteen patients (76.2%) had CR, three patients had PR (14.3%), with the OR being 90.5%. At month six, 16 of 21 patients (76.2%) had achieved CSR. Seven patients received a second course of dexamethasone (one at day +8 and six at day+15) (Table 1). The median duration of response was 12 months (range, 7–25 months). The median time to reach TTR and TCR was 8 days (range, 4–28). Partial response was achieved in two patients who were further treated with danazol and prednisone, being subsequently splenectomized. The relapse rate was 15.8%. The 6- and 12- month cumulative RFS were both 84%; the 6- and 12-month cumulative TFS probabilities were 94% and 87%, respectively (Fig. 1). Overall, combination therapy in our group was well tolerated with a lower incidence of adverse effects during infusion in this trial according to the data reported in previous studies. Conclusions The combination of low-dose rituximab and high-dose dexamethasone as front-line therapy for adults with ITP was effective and safe with a high OR rate and a low incidence of relapse. These data need to be confirmed in a prospective randomized clinical trial including a sample size with enough power to reach statistically significant conclusions. Disclosures: No relevant conflicts of interest to declare.

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High Dose Dexamethasone Vs. Conventional Dose Prednisolone for Adults with Immune Thrombocytopenia: a Prospective Multicenter Phase III Trial.

Blood ◽

10.1182/blood.v116.21.3687.3687 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3687-3687 ◽

Cited By ~ 12

Author(s):

Sung Hwa Bae ◽

Hun-Mo Ryoo ◽

Won Sik Lee ◽

Young Don Joo ◽

Kyoo Hyung Lee ◽

...

Keyword(s):

Platelet Count ◽

Initial Treatment ◽

Immune Thrombocytopenia ◽

Response Rate ◽

Sustained Response ◽

Adult Patients ◽

Phase Iii ◽

High Dose ◽

Sustained Response Rate ◽

High Dose Dexamethasone

Abstract Abstract 3687 Background: Prednisolone at a dose of 1 mg/kg/day (PRD) for 2 to 4 weeks is administered as front-line therapy to most adult patients with immune thrombocytopenia (ITP) who need to be treated. Recent results from 2 large single arm studies suggest high dose dexamethasone (DEX) as first-line treatment may produce a high sustained response rate. Therefore, we conducted prospective randomized trial comparing DEX with PRD as initial treatment of adult patients with newly diagnosed ITP. Methods: We did a randomized multicentre trial based on a 1:1 design. We enrolled treatment-naïve patients, 16 years or older, with a diagnosis of ITP according to the practice guidelines of the American Society of Hematology and a platelet count of 30×109/L or less. Patients with ITP were randomly assigned to receive either DEX 40 mg/day on day 1–4 (If the platelet count dropped below 3×109/L within the first six months, another four-day course of DEX was given) or PRD 1mg/kg/day for 4 weeks. The primary object of this study was the sustained response (platelet count>30×109/L after 6 months) rate. Second objectives are response rate at 4 weeks, predictors of steroid response, and toxicity. This study is registered at http://clinicaltrials.gov as NCT00451594. Results: From September 2005 to December 2009, 151 adults with ITP were randomly assigned (76 patients in the DEX arm, 75 patients in the PRD arm). Overall demographics were balanced between arms; Median age 44 years old (DEX:PRD 44 years old:44 years old); 69.5% female (DEX:PRD 73.7%:65.3%); median initial platelet count 17×109/L (DEX:PRD 16×109/L:17×109/L). Of 151 enrolled patients, 117 patients (57 patients in the DEX arm, 60 patients in the PRD arm) were evaluable in terms of sustained response. Sustained response rate by intention-to-treat (ITT) and per protocol were 25.0% and 33.3% in the DEX arm, 36.0% and 45.0% in the PRD arm, respectively (p=0.33 by ITT). Eight patients in the DEX arm and 17 patients in the PRD arm had a sustained platelet counts more than100×109/L. Fifteen patients had a sustained response after a single course of DEX and 6 patients among them required no further treatment during two to four year follow up. Median time to relapse in patients who had a sustained response was 1320 days and 1140 days, respectively. The response rate at day 28 was 68.2% in the DEX arm and 81.2% in the PRD arm. Pre-treatment platelet count was higher in patients who achieved sustained response (responder vs. non-responder: 17.1±7.8×109/L vs. 15.9±8.9×109/L). Eleven patients in the DEX arm and 8 patients in the PRD arm received splenectomy. Both treatments were well tolerated. Three patients represented side effects that were severe enough to discontinue the treatment in the PRD arm, including pneumonia (1), hyperglycemia (1), and myalgia (1). Six patients receiving DEX and 5 patients receiving PRD had G3 or more hyperglycemia. Conclusion: One or two courses of DEX were not more effective than PRD in adults with ITP. However, 19.7% of adult ITP had a sustained response with a single course of DEX. Initial treatment with DEX could be useful for identifying patients who may not require prolonged steroid treatment. Disclosures: No relevant conflicts of interest to declare.

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Reduced-Dosage of Three Drugs Combination of Cyclophosphamide, Bortezomib and Dexamethasone (reduced-CyBorD) Retains High Response Rate with Less Toxicities in Elderly Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v120.21.1865.1865 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1865-1865 ◽

Cited By ~ 1

Author(s):

Hideo Yagi ◽

Ryosuke Fujiwara ◽

Keigo Sano ◽

Fujita Mariko ◽

Takashi Iizuka ◽

...

Keyword(s):

Multiple Myeloma ◽

Adverse Events ◽

Elderly Patients ◽

Response Rate ◽

Conflicts Of Interest ◽

High Response Rate ◽

High Response ◽

High Dose ◽

Weekly Schedule ◽

High Dose Dexamethasone

Abstract Abstract 1865 Background: The three drugs combination of cyclophosphamide, bortezomib and dexamethasone (CyBorD) has been proven to be a powerful regimen for the treatment of the patients with multiple myeloma (MM). However, twice-weekly schedule of bortezomib and high dose dexamethasone has been shown to cause significant toxicities, including severe peripheral neuropathy (PN). Recently, once-weekly bortezomib induction therapy with CyBorD (modified-CyBorD) has shown less toxicity with high response rate equal to original regimen (Reeder, CB et al. Leukemia 2009). However, more than half of the patients developed bortezomib induced PN (BiPN) in modified-CyBorD. Thus it was still concerned adverse event for the transplant ineligible patients, especially frail elderly patients because it often caused interruption or withdrawal of the treatments, resulting in fewer efficacies. Under these circumstances, we introduced the reduced-dosage of CyBorD regimen (reduced-CyBorD) in the transplant ineligible patients with multiple myeloma for continuation of the treatment. Methods: The protocol consisted of bortezomib given intravenously at a dose of 1.3 mg/m2once a week on days 1, 8, 15, cyclophosphamide orally at a dose of 50 mg daily on days 1–21, and dexamethasone orally or intravenously at a dose of 20 mg daily on days 1,2,8,9,15,16 in 4-week cycles. Total of 20 patients, including 12 newly diagnosed and 8 refractory, were treated with reduced-CyBorD and evaluated its efficacy and safety. Results: The median age was 72 years (range from 62 to 81). 14 patients were more than 70 year-old (70%). A half of the patients were female. According ISS, 3 patients were classified in stage I, 6 were in II, and 11 were in III. The overall response was 86.6 % with 26.7 % CR/nCR (1 CR, 3 nCR, 5 VGPR and 4 PR). Hematological adverse events were neutropenia (35%; G1/2 n=7), lymphocytopenia (35%; G1/2 n=1, G3/4, n=1), thrombocytopenia (10%; G1/2 n=2). Non-hematological adverse events were pneumonia (20%; G2 n=2, G3 n=2), VZV infection (15%; G2 n=3), cerebral infarction (5%; G2 n=1). Importantly, only three patients (15%) developed grade 1 PN, and no patient reduced or discontinued bortezomib due to PN. Conclusions: Reduced-CyBorD with three times once-weekly bortezomib retained high efficacy seen in standard and modified CyBorD (4 times bortezomib administration). Furthermore, it was found that this regimen obviously revealed less toxicity, especially BiPN compared with those previous regimens (See Table). Our results suggested that reduced-CyBorD might be safe and effective approach to the transplant ineligible patients, especially elderly frail patients with MM. Disclosures: No relevant conflicts of interest to declare.

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