scholarly journals Ofatumumab and high-dose methylprednisolone for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia

2014 ◽  
Vol 4 (11) ◽  
pp. e258-e258 ◽  
Author(s):  
J E Castro ◽  
M Y Choi ◽  
T Carvajal ◽  
E Almahasnah ◽  
J Chang ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
High Dose Methylprednisolone

Rituximab® and High Dose Methylprednisolone (HDMP) for the Treatment of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2518-2518
Author(s):  
Januario E. Castro ◽  
Jan Bole ◽  
Carlos E. Prada ◽  
Thomas J. Kipps
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Performance Status ◽  
Variable Region ◽  
Response Assessment ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Ecog Performance Status ◽  
Female Ratio ◽  
High Dose Methylprednisolone

Abstract High-dose gluocorticoids and the anti-CD20 mAb Rituximab each can effect partial responses in patients with chronic lymphocytic leukemia (CLL), although complete and durable responses to treatment with either of these agents have not been reported. We examined whether patients with relapsed and/or refractory CLL could respond to these agents when used in combination in a pilot clinical trial. Fourteen patients with progressive, symptomatic, and relapsed/refractory disease were treated with three four-week cycles of high-dose Methylprednisolone (HDMP) at 1gr/m2 daily for 5 days and weekly Rituximab® at 375mg/m2 for four weeks. The median age of the patients was 60 years, the male to female ratio was 4:1, the ECOG performance status was < 2, and the average number of prior treatments was 2. All patients failed or were intolerant to fludarabine and 86% had high-risk disease by the modified Rai classification. Sixty-five percent of the patients had CLL cells that expressed ZAP-70 and unmutated immunoglobulin variable region genes. Response assessment was performed at the end of each cycle, two months after completion of treatment, and each 3–6 months thereafter until the patients experienced disease progression and/or required further treatment. Objective responses were observed in all 14 patients, with 6 patients achieving a complete response (CR) and the remainder a partial response (PR) as per the NCI-working group criteria. We observed a significant decrease in peripheral white blood cell (WBC) counts, increase in hemoglobin, elevation of platelet counts and a dramatic decrease in lymphadenopathy and splenomegaly. Five of the treated patients have not required further treatment with a median follow up of 26 months. Of these 5 patients 3 have maintain a CR. The median time to progression (TTP) was 12 months. Overall, the treatment was well tolerated and all the patients, except one, completed 3 cycles of therapy. The majority of adverse events were Grade I-II (fluid retention, cough, transient hyperglycemia, fatigue). In addition, we observed 7 episodes of grade III-IV toxicity secondary to (anemia, CMV esophagitis and GI bleeding with one case each and two cases each of thrombocytopenia and neutropenia). These data suggest that treatment with the combination of Rituximab® and HDMP has increased activity over treatment with either agent alone and may produce durable complete responses in patients with refractory and / or relapsed CLL.

A Phase Ib/II Study of Combined Obinutuzumab (Gazyva) and High-Dose Methylprednisolone (HDMP) As Treatment for Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2051-2051 ◽  
Author(s):  
Januario E. Castro ◽  
Michael Y. Choi ◽  
Carlos I. Amaya-Chanaga ◽  
Natalie Nguyen ◽  
Colin MacCarthy ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
High Dose ◽  
Free Survival ◽  
Phase Ib ◽  
High Dose Methylprednisolone ◽  
Grade 3

Abstract High-dose methylprednisolone (HDMP) and rituximab (R) is an effective non-myelosuppressive treatment regimen for patients (pts) with chronic lymphocytic leukemia (CLL). Also, this combination has shown activity even in pts who have adverse leukemia-cytogenetics, such as del17p. Phase III studies have demonstrated that CLL pts treated with chlorambucil and obinutuzumab-Gazyva (G), another anti-CD20 mAb, had a superior outcome than comparable pts treated with R-chlorambucil. We hypothesized that G-HDMP is well-tolerated and effective in the treatment of pts with CLL. Accordingly, we initiated an open-label phase Ib/II clinical study. A total of 40 pts were enrolled in two cohorts of 20 pts each (previously untreated (PU) and relapsed/refractory (RR) CLL) and treated with HDMP 1 g/m2on Day 1-3 of cycles 1-4 (28 days/cycle) and G administered based on FDA dosing recommendations for 6 cycles. The pts had a median age of 67 years + 9.1 in the RR cohort and 63 years + 8.3 in the PU cohort. The median baseline absolute lymphocyte count was 30.7 + 7.3 x1,000/mm3 for pts in the RR cohort and 47.6 + 19.7 x1,000/mm3for pts in the PU cohort. Pts showed the following cytogenetic abnormalities: del(17p) in 30% RR vs. 0% PU, del(13q) in 60% RR vs. 70% PU, del(11q) in 20% RR vs. 35% PU, and trisomy 12 in 15% RR vs. 20% PU. Most AEs were grade 1-2 (RR=87%; PU=93%) without development of dose-limiting toxicities. Only two pts needed therapy discontinuation. One pt due to pulmonary embolism and the second pt due to asymptomatic gastrointestinal bleeding that required blood transfusion and resolved spontaneously. Grade 1-2 G-infusion-related reactions (IRR) were observed in 40% and 80% of pts in the RR and PU cohorts, respectively. Grade 3-4 IRR were observed in 10% of pts in the PU cohort only. We observed cytopenias (neutropenia grade 3-4: RR=55%, PU=40%; thrombocytopenia grade 3-4: RR=35%, PU=20%; and anemia grade 3-4: RR=0%, PU=0%). There were no cases of febrile neutropenia. Two pts (10%) in the RR cohort and one pt (5%) in the PU cohort developed infection grade 1-2 that was treated with oral antibiotics but did not require study treatment discontinuation. The most frequent non-hematological adverse events (AEs) were transaminitis, hyperglycemia, and electrolyte alterations (grade 1-2). There were no treatment related deaths in either cohort. The response assessment was performed in all 40 pts by iwCLL criteria. The ORR was 100% in the PU cohort and 95% in the RR cohort. 70% of the pts in the PU cohort and 85% of the pts in the RR cohort achieved a PR. CR was observed in 30% and 10% of the pts in the PU and RR cohorts, respectively. One pt (5%) in the RR cohort and four pts (20%) in the PU cohort achieved MRDneg status (<0.01% CLL in the bone marrow by multiparameter flow cytometry). Only one pt in the RR cohort achieved SD. At a median follow-up of 12.2 months, the RR cohort had a median Progression Free Survival (PFS) of 13.6 months and median Treatment Free Survival (TFS) of 14.7 months; the median Overall Survival (OS) has not been reached. In the PU cohort, the median PFS, TFS and OS have not been reached. One pt from the RR cohort and one pt from the PU cohort died during the follow-up period due to disease progression. G-HDMP was well tolerated and all 40 pts showed hematological and clinical responses during the study treatment without development of unexpected AEs. In both cohorts, most of IRR were grade 1-2 and severe IRR (grade 3-4) were much less compared with previously published data (G-chlorambucil / CLL-11 study). Compared to pts in the CLL-11 study, cytopenias appeared to be more frequent, however, the rate of infection and need for IV antibiotics or hospitalizations was lower. Of note, the eligibility criteria allowed pts with severe cytopenias and transfusion requirement to participate in our study. Response in PU pts were higher in terms of ORR, CR and CR-MRDnegativecompared with the data from the CLL-11 study and suggests a possible synergistic activity between G and HDMP. Overall, G-HDMP was well tolerated in the PU and RR CLL pts with a lower rate of IRR making this regimen more manageable in the outpatient setting. Responses were higher than previously reported in PU pts. Responses in RR pts appear to be comparable to our previous studies using R-HDMP. Our data supports G-HDMP as an alternative combination regimen for the treatment of CLL pts. Disclosures Kipps: Celgene: Consultancy, Honoraria, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria.

scholarly journals Dose Intensive Rituximab and High-Dose Methylprednisolone in Elderly or Unfit Patients with Relapsed Chronic Lymphocytic Leukemia

Medicina ◽  
2019 ◽  
Vol 55 (11) ◽  
pp. 719
Author(s):  
Pileckyte ◽  
Valceckiene ◽  
Stoskus ◽  
Matuzeviciene ◽  
Sejoniene ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Meaningful Improvement ◽  
Free Survival ◽  
High Dose Methylprednisolone ◽  
Unfit Patients

Background and Objectives: BTK and BCL2 inhibitors have changed the treatment paradigms of high-risk and elderly patients with chronic lymphocytic leukemia (CLL), but their long-term efficacy and toxicity are still unknown and the costs are considerable. Our previous data showed that Rituximab (Rtx) and high-dose methylprednisolone (HDMP) can be an effective and safe treatment option for relapsed high-risk CLL patients. Materials and Methods: We explored the efficacy and safety of a higher Rtx dose in combination with a shorter (3-day) schedule of HDMP in relapsed elderly or unfit CLL patients. Results: Twenty-five patients were included in the phase-two, single-arm trial. The median progression free survival (PFS) was 11 months (range 10–12). Median OS was 68 (range 47–89) months. Adverse events (AE) were mainly grade I–II° (77%) and no deaths occurred during the treatment period. Conclusions: 3-day HDMP and Rtx was associated with clinically meaningful improvement in most patients. The median PFS in 3-day and 5-day HDMP studies was similar and the toxicity of the 3-day HDMP schedule proved to be lower. The HDMP and Rtx combination can still be applied in some relapsed high-risk and elderly or unfit CLL patients if new targeted therapies are contraindicated or unavailable. (ClinicalTrials.gov identifier: NCT01576588).

Rituximab® and High Dose Methylprednisolone (HDMP) as a First Line Treatment for Patients with Chronic Lymphocytic Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2969-2969
Author(s):  
Januario E. Castro ◽  
Jan E. Bole ◽  
Carlos E. Prada ◽  
Olivier Loria ◽  
Thomas J. Kipps
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Working Group ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Combination Regimen ◽  
Line Treatment ◽  
First Line ◽  
Female Ratio ◽  
High Dose Methylprednisolone ◽  
First Line Treatment

Abstract High-dose methylprednisolone (HDMP) and the anti-CD20 mAb Rituximab® each can effect partial responses in patients with chronic lymphocytic leukemia (CLL). Previously, we noted that these two agents used in combination were highly effective in treating CLL patients with relapse/refractory disease. We examined whether patients with CLL could respond to these agents when used in combination as a first line therapy. To mitigate the toxicity associated with HDMP, the dose of methylprednisolone was reduced to 60% of that used in salvage regimens. Sixteen patients with CLL were treated with three four-week cycles of methylprednisolone at 1 gm/m2 daily for 3 days and weekly Rituximab® at 375 mg/m2 for four weeks. All patients satisfied NCI-working group criteria for requiring treatment. The median age of the patients was 60 years, the male to female ratio was 4:1, the ECOG performance status was ? 2. Eighty-six percent of the patients had high-risk disease prior to therapy, as per the modified Rai classification. Fifty-six percent of the patients had CLL cells that expressed ZAP-70 and/or unmutated immunoglobulin variable region genes. Response assessment was performed at the end of each cycle, two months after completion of treatment, and each 3–6 months thereafter until the patient experienced disease progression and/or required further treatment. Objective responses were observed in 14 out of 16 patients (Overall response rate 93%), with 1 patient achieving a complete response (CR) without disease detectable in the marrow, 1 patient achieving a nodular PR, 12 patients obtaining an excellent PR only with minimal residual disease in the bone marrow, and 1 patient having stable disease, as per the NCI-working group criteria. We observed significant reductions in the white blood cell (WBC) counts, increases in hemoglobin, elevations in platelet counts, and dramatic reduction and resolution in lymphadenopathy and splenomegaly. The median time to progression (TTP) after 12 months of follow up has not been reached. Overall, the treatment was well tolerated and all but one patient completed 3 cycles of therapy. Most adverse events were Grade I-II (fluid retention, cough, transient hyperglycemia, fatigue). We also observed 2 transient episodes of grade III–IV toxicity secondary to infection, resulting in pneumonia or sinusitis that resolved completely after antibiotic treatment. Pharmacodynamic studies showed that leukemia cells from patients responding to this combination regimen were induced to express pro-apoptotic molecules, such as Bid, Apaf-1, Smac-Diablo, and to downregulate expression of anti-apoptotic molecules, such as XIAP and Mcl-1. These data indicate that modified-dose HDMP/Rituximab® may be an effective and well-tolerated first line treatment for patients with CLL.

Sign in / Sign up

Export Citation Format

Share Document