Phase II Clinical Study of Cladribine in the Treatment of Hairy Cell Leukemia

Machii, Takashi; Chou, Takaaki; Suzuki, Masane; Ohe, Yokiko; Katagiri, Seiji; Kitano, E; Kitano, Kiyoshi; Fujiyama, Yoshihide; Izumi, Tohru; Shimazaki, Chihiro; Nanba, Kôji; Ohashi, Yasuo; Kitani, Teruo

doi:10.1532/ijh97.04128

Cited by 11 publications

(7 citation statements)

References 22 publications

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“…Thus 9 (90%) of 10 patients achieved CR with cladribine and immediate rituximab, compared to only 8% of 39 historical HCLv patients reported from 6 retrospective studies using cladribine alone (6–11) (p<0.0001). These retrospective reports of cladribine alone in HCLv included 4 PRs out of 8 (6), 2 PRs out of 6 (34), 1 CR and 2 PRs out of 4 (8), 1 PR out of 3 (9), 1 CR and 2 PRs out of 3 (10), and 1 CR and 3 PRs out of 15 (11) patients. In the present study with Cladribine combined with immediate rituximab, all 9 CRs maintained evidence of CR by restaging studies at 12–48 (median 30) months of follow-up.…”

Section: Resultsmentioning

confidence: 99%

Cladribine with Immediate Rituximab for the Treatment of Patients with Variant Hairy Cell Leukemia

Kreitman

Wilson

Calvo

et al. 2013

Clinical Cancer Research

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Purpose In contrast to the classic form, variant hairy cell leukemia (HCLv) responds poorly to single-agent purine analogs, expresses unmutated BRAF, has shorter overall survival, and lacks effective standard therapy. No treatment has achieved a high complete remission rate even in small series, and of 39 reported cases from 6 studies, overall response rate after cladribine was 44% with 8% complete remissions. Rituximab has been found to increase the sensitivity of malignant cells to cladribine, suggesting that combination with cladribine might improve response in HCLv. To test this hypothesis, HCLv patients were treated with simultaneous cladribine and rituximab. Experimental design HCLv patients with 0-1 prior courses of cladribine received cladribine 0.15 mg/Kg days 1–5, with 8 weekly doses of rituximab 375 mg/m2 beginning day 1. Restaging was performed, and minimal residual disease (MRD) in blood and marrow was quantified using PCR, immunohistochemistry, and flow cytometry. Results By 6 months, 9 (90%) of 10 patients achieved complete remission (CR), compared to 3 (8%) of 39 reported cases treated with cladribine alone (p<0.0001). Of the 9 CRs, 8 remain free of MRD at 12–48 (median 27) months of follow-up. No dose-limiting toxicities were observed when beginning cladribine and rituximab on the same day, although most patients required short-term steroids to prevent and treat rituximab infusion reactions. Cytopenias in CRs resolved in 7–211 (median 34) days without major infections. Conclusion Although cladribine alone lacks effectiveness for early or relapsed HCLv, cladribine with immediate rituximab achieves CRs without MRD and is feasible to administer.

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Section: Resultsmentioning

confidence: 99%

Cladribine with Immediate Rituximab for the Treatment of Patients with Variant Hairy Cell Leukemia

Kreitman

Wilson

Calvo

et al. 2013

Clinical Cancer Research

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“…HCL‐v needs a specific mention as it responds poorly to cladribine monotherapy, with a CR rate of 8% and ORR of 44% in the largest reported studies (Robak et al , ; Tetreault et al , ; Matutes et al , ; Palomera et al , ; Machii et al , ; Arons et al , ). It also responds poorly to therapy with pentostatin (Matutes et al , ).…”

Section: Improving On Initial Purine Analogue Monotherapy In the Firsmentioning

confidence: 99%

How I manage patients with hairy cell leukaemia

Thompson

Ravandi

2017

Br J Haematol

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Patients with hairy cell leukaemia (HCL) have highly favourable outcomes after purine analogue therapy. However, most patients subsequently relapse and require re-treatment. A minority of patients develop purine analogue-refractory disease. Targeted therapies have improved outcomes for such patients. Recently, the BRAF V600E mutation was identified in most patients with classical HCL, resulting in constitutive mitogen-activated protein kinase pathway activation; impressive responses are achieved in heavily pre-treated patients with BRAF inhibition. The CD22-targeted immunoconjugate moxetumomab pasudotox and BTK inhibitor ibrutinib also achieve responses in relapsed and refractory patients. HCL variant and the IGHV4-34 molecular variant of HCL lack BRAF mutation and have inferior outcomes with standard purine analogue therapy. The addition of rituximab to purine analogues achieves very high rates of minimal residual disease-negative complete remission and improves outcomes for patients with HCL variant. Given the rarity of HCL, optimal integration of novel therapies into treatment algorithms will require well-designed, collaborative studies.

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“…HCLv responds poorly to purine analog monotherapy and OS is 6–9 years compared to >25 years for classic HCL [ [61] , [62] , [63] , 65 , 67 , 125 , 126 ].. Of 42 historical HCLv patients who received cladribine monotherapy, the CR rate was only 7% [ 20 , [126] , [127] , [128] , [129] , [130] ]. At MD Anderson Cancer Center, 7 HCLv patients received 1 st -line treatment with cladribine followed 4 weeks later by 8 weekly doses of rituximab with a CR rate of 86% and MRD-free CR rate of 71% [ 64 , 120 ].…”

Section: First-line Treatment Of Hclmentioning

confidence: 99%

Diagnosis and treatment of hairy cell leukemia as the COVID-19 pandemic continues

Kreitman

Arons

2022

Blood Reviews

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Hairy cell leukemia (HCL) is an indolent B-cell malignancy, usually driven by the BRAF V600E mutation. For 30 years, untreated and relapsed HCL was successfully treated with purine analogs, but minimal residual disease (MRD) remained in most patients, eventually causing relapse. Repeated purine analogs achieve decreasing efficacy and increasing toxicity, particularly to normal T-cells. MRD-free complete remissions (CRs) are more common using rituximab with purine analogs in both 1 st -line and relapsed settings. BRAF inhibitors and Ibrutinib can achieve remission, but due to persistence of MRD, must be used chronically to prevent relapse. BRAF inhibition combined with Rituximab can achieve high MRD-free CR rates. Anti-CD22 recombinant immunotoxin moxetumomab pasudotox is FDA-approved in the relapsed setting and is unique in achieving high MRD-free CR rates as a single-agent. Avoiding chemotherapy and rituximab may be important in ensuring both recovery from COVID-19 and successful COVID-19 vaccination, an area of continued investigation.

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Phase II Clinical Study of Cladribine in the Treatment of Hairy Cell Leukemia

Cited by 11 publications

References 22 publications

Cladribine with Immediate Rituximab for the Treatment of Patients with Variant Hairy Cell Leukemia

Cladribine with Immediate Rituximab for the Treatment of Patients with Variant Hairy Cell Leukemia

How I manage patients with hairy cell leukaemia

Diagnosis and treatment of hairy cell leukemia as the COVID-19 pandemic continues

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