Risk factors for severe infection in patients with hairy cell leukemia: a long-term study of 73 patients

Abstract Background Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL). Methods Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days. Results Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported. Conclusions Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy. Trial registration ClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT01829711

Download Full-text

Hairy Cell Leukemia: Long Term Response to Cladribine

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2018.07.211 ◽

2018 ◽

Vol 18 ◽

pp. S280

Author(s):

Anup Devasia ◽

Anu Korula ◽

Uday Kulkarni ◽

Fouzia NA ◽

Aby Abraham ◽

...

Keyword(s):

Hairy Cell Leukemia ◽

Hairy Cell ◽

Cell Leukemia ◽

Term Response

Download Full-text

Relapse of hairy cell leukemia after 2-chlorodeoxyadenosine: long-term follow-up of the Northwestern University experience

Blood ◽

10.1182/blood.v88.6.1954.bloodjournal8861954 ◽

1996 ◽

Vol 88 (6) ◽

pp. 1954-1959 ◽

Cited By ~ 73

Author(s):

MS Tallman ◽

D Hakimian ◽

AW Rademaker ◽

C Zanzig ◽

E Wollins ◽

...

Keyword(s):

Relapse Rate ◽

Hairy Cell Leukemia ◽

Progression Free Survival ◽

Hairy Cell ◽

Cell Leukemia ◽

Term Outcome ◽

Long Term Outcome ◽

Prior Therapy ◽

Long Term Follow Up

Although 2-chlorodeoxyadenosine (2-CdA) is effective in inducing complete remissions (CRs) in the majority of patients with hairy cell leukemia (HCL), neither the actual relapse rate, the clinical factors that may predict relapse, the long-term outcome, nor the response rate to re-treatment at relapse has been clearly determined. Fifty-two consecutive patients with previously untreated or treated HCL were treated with 2-CdA at a dose of 0.1 mg/kg/d by continuous intravenous infusion for 7 days. Of 50 assessable patients, 40 (80%) achieved CR, and 9 (18%) achieved partial remission (PR). A total of 7 patients (14%) have relapsed, at a median duration of 24 months (range, 12 to 44). Of the 7 relapsed patients, 5 were re-treated with a second cycle of 2-CdA; 2 achieved a second CR and 3 attained a PR. The progression- free survival (PFS) rate is 72% at 4 years for all 52 patients and 83% for patients achieving CR. The overall survival (OS) rate is 86% at 4 years. Only prior therapy was predictive of relapse. The majority of patients achieve durable CRs with a single cycle of 2-CdA. The relapse rate is low and the long-term prognosis is excellent. The few patients who relapse can attain second remissions after re-treatment with 2-CdA.

Download Full-text

Long-term results of alpha interferon as initial therapy and splenectomy as consolidation therapy in patients with hairy cell leukemia. Final report from the Italian Cooperative Group for HCL

Annals of Oncology ◽

10.1093/oxfordjournals.annonc.a058977 ◽

1994 ◽

Vol 5 (8) ◽

pp. 725-731 ◽

Cited By ~ 17

Author(s):

M. Federico ◽

A. Frassoldati ◽

T. Lamparelli ◽

R. Foà ◽

M. Brugiatelli ◽

...

Keyword(s):

Hairy Cell Leukemia ◽

Initial Therapy ◽

Alpha Interferon ◽

Long Term Results ◽

Final Report ◽

Cooperative Group ◽

Consolidation Therapy ◽

Hairy Cell ◽

Cell Leukemia

Download Full-text

Incidence of response and long-term follow-up in patients with hairy cell leukemia treated with recombinant interferon alfa-2a [see comments]

Blood ◽

10.1182/blood.v75.4.839.839 ◽

1990 ◽

Vol 75 (4) ◽

pp. 839-845 ◽

Cited By ~ 67

Author(s):

E Berman ◽

G Heller ◽

S Kempin ◽

T Gee ◽

LL Tran ◽

...

Keyword(s):

Disease Progression ◽

Hairy Cell Leukemia ◽

Interferon Alfa ◽

Hairy Cell ◽

Cell Leukemia ◽

Minor Response ◽

Recombinant Interferon ◽

Long Term Follow Up

Abstract Thirty-five evaluable patients with hairy cell leukemia (HCL) were treated with recombinant interferon alfa-2a (rIFN-alpha 2a), given at a dose of 3 X 10(6) units (U) intramuscularly (IM) daily for 6 months followed by 3 X 10(6) U IM three times a week for an additional 18 months in a single institution study. All treatment was stopped after 24 months. Sixty-nine percent of patients achieved a partial response, 11% a minor response, and 3% (one patient) had stable disease. Six patients (17%) did not respond to rIFN-alpha 2a. Two patients (6%) achieved a response but later progressed on treatment. A total of 23 patients completed 2 years of treatment and are evaluable for long-term follow-up at a median of 20 months postcompletion of therapy (range 9 to 32 months). Eleven patients (48%) have had progression of their disease at a median of 10 months (range .5 to 25 months) after treatment was discontinued. Statistical analysis of pretreatment patient characteristics did not reveal any factor(s) associated with a high probability of responding to rIFN-alpha 2a; however, analysis of post-treatment variables measured after 2 years of treatment suggested that a low platelet count was associated with a high rate of disease progression. These findings are compared with other published trials using rIFN-alpha 2b, a similar but not identical rIFN preparation. We conclude that while rIFN-alpha 2a has a high overall response incidence, the rate of disease progression after therapy is discontinued approaches 50%, and that a subset of patients can be identified who are at high risk for recurrence after completing 2 years of treatment.

Download Full-text

Long-Term Follow-Up of Patients With Hairy Cell Leukemia After Cladribine Treatment

Blood ◽

10.1182/blood.v92.6.1918 ◽

1998 ◽

Vol 92 (6) ◽

pp. 1918-1926 ◽

Cited By ~ 207

Author(s):

Alan Saven ◽

Carol Burian ◽

James A. Koziol ◽

Lawrence D. Piro

Keyword(s):

Hairy Cell Leukemia ◽

Survival Rates ◽

Complete Response ◽

Hairy Cell ◽

Cell Leukemia ◽

Second Neoplasms ◽

American Society ◽

La Jolla

Abstract Hairy cell leukemia is a chronic B-cell disorder that follows an indolent, but progressive course. Cladribine (2-chlorodeoxyadenosine) induces complete remissions in the majority of patients after a single course. We report the long-term outcomes, including response rates and their duration; time-to-treatment failure (TTF) rates; retreatment results; toxicities; and survival rates of patients treated at Scripps Clinic (La Jolla, CA). A total of 358 patients with hairy cell leukemia were treated with cladribine at 0.087 or 0.1 mg/kg body weight per day by continuous intravenous infusion for 7 days. The expected number of second neoplasms was based on the National Cancer Institute’s Surveillance Epidemiology and End Results data. Of 349 evaluable patients, 319 (91%) achieved an initial complete response and 22 (7%) a partial response with an overall median duration of response follow-up of 52 months. Ninety patients (26%) had relapsed at a median of 29 months. The TTF rate for all 341 responders was 19% at 48 months, 16% for complete responders, and 54% for partial responders. Of 53 evaluable patients treated with second courses of cladribine at first relapse, 33 (62%) achieved complete responses and 14 (26%) partial responses. Twenty-seven patients (8%) developed second neoplasms (only 1 hematopoietic) with an observed-to-expected ratio of 1.88 (95% confidence interval, 1.24 to 2.74). The overall survival rate was 96% at 48 months. Single courses of cladribine induced long-lasting complete responses in the vast majority of patients. Relapse rates for complete responders were low. Patients who relapse can be successfully retreated with cladribine. Cladribine has high efficacy and a favorable acute and long-term toxicity profile when administered to patients with hairy cell leukemia. © 1998 by The American Society of Hematology.

Download Full-text