The current role of interferon in hairy cell leukaemia: clinical and molecular aspects

Assanto, Giovanni Manfredi; Riemma, Costantino; Malaspina, Francesco; Perrone, Salvatore; Luca, Maria Lucia De; Pucciarini, Alessandra; Annechini, Giorgia; D’Elia, Gianna Maria; Martelli, Maurizio; Foà, Robin; Tiacci, Enrico; Pulsoni, Alessandro

doi:10.1111/bjh.17440

Cited by 10 publications

(5 citation statements)

References 16 publications

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“…Almost one-third of patients in our series were treated first-line with IFN-α at varying dosages adjusted according to toxicities and disease control. We report a high ORR (87.5%) and relatively low CRu rate (20.8%) similar to efficacy data documented in a recent analysis [ 12 ]. Without additional myelotoxicity, no infection prophylaxis was given, and no infectious complications were reported.…”

Section: Discussionsupporting

confidence: 90%

Hairy Cell Leukemia Patients Have a Normal Life Expectancy—A 35-Year Single-Center Experience and Comparison with the General Population

Bohn

Neururer

Pirklbauer

et al. 2022

Cancers

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Classic hairy cell leukemia (HCL) is an uncommon hematologic malignancy characterized by an excellent prognosis since purine analogues (PA), such as cladribine (2-CdA), have been introduced in the 1990s. However, most data on long-term outcomes is gathered from patients treated with PA first-line or include limited information on previous treatment outcomes, i.e., Interferon-α (IFN-α). Survival curves from previous series did not reach a plateau, indicating that nearly all patients ultimately relapse. Yet, overall survival (OS) data were rarely corrected for life expectancy of the general population. We here report 83 consecutive HCL patients treated between 1983 and 2017 at the University Center in Innsbruck, Austria. Median follow-up was 170 months (1–498). IFN-α, the first-line treatment of choice before 1990, was administered to 24 patients, achieving an overall response rate (ORR) of 86% and an unconfirmed complete remission (CRu) in 23%. All these patients relapsed after a median progression-free survival (PFS) of 30 months (3–80), but either remained drug-sensitive upon re-exposure to IFN-α or were successfully salvaged with PA. All 42 patients exposed to first-line 2-CdA responded (ORR of 100%). Sixteen patients received two to four successive courses of PA with a continuous decrease in the response quality (CRu rate 85.7% 1st-line vs. 41.5% 3rd-line treatment). Median PFS was not reached in both treatment-naïve patients and those retreated at first relapse. Although pretreatment with IFN-α was associated with a shortened median PFS of 81 months (43–118) after PA therapy, this tendency of inferior PFS did not result in inferior OS. OS of all 83 patients was excellent and equivalent to that of age-, sex-, and diagnostic period-matched controls from the Tyrolean general population (standardized mortality ratio 0.8), regardless of their age at diagnosis or whether they were diagnosed until or after the year 2000. These results confirm that HCL patients may look forward to a normal lifespan when treated with PA irrespective of their pretreatment history.

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Section: Discussionsupporting

confidence: 90%

Hairy Cell Leukemia Patients Have a Normal Life Expectancy—A 35-Year Single-Center Experience and Comparison with the General Population

Bohn

Neururer

Pirklbauer

et al. 2022

Cancers

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“… 8 Nonmyelotoxic agents suitable for refractory/relapsed HCL are rituximab and interferon-α, but they usually produce few CRs. 11 , 12 Moreover, interferon-α production has been even discontinued, although its pegylated formulation is available off-label.…”

Section: Introductionmentioning

confidence: 99%

How I treat refractory/relapsed hairy cell leukemia with BRAF inhibitors

Falini

Carolis

Tiacci

2022

Blood

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Hairy cell leukemia (HCL) responds very well to frontline chemotherapy with purine analogs (cladribine and pentostatine). However, about half of patients experience one or more relapses, which become progressively resistant to these myelotoxic and immunosuppressive agents. At progression, standard therapeutic options include a second course of purine analogs alone or in combination with rituximab, and, upon second relapse, therapy with the anti-CD22 immunotoxin moxetumomab pasudotox. Furthermore, blockade of the mutant BRAF-V600E kinase (the pathogenetic hallmark of HCL) through orally available specific inhibitors (vemurafenib or dabrafenib) effaces the peculiar morphologic, phenotypic and molecular identity of this disease as well as its typical anti-apoptotic behaviour, and is emerging as an attractive chemotherapy-free strategy in various clinical scenarios. These include patients with, or at risk of, severe infections and, in a highly effective combination with rituximab, patients with relapsed or refractory HCL. Other treatments explored in clinical trials are BTK inhibition with ibrutinib and co-inhibition of BRAF (through dabrafenib or vemurafenib) and its downstream target MEK (through trametinib or cobimetinib). Here, we focus on our experience with BRAF inhibitors in clinical trials and as off-label use in routine practice by presenting three challenging clinical cases to illustrate their management in the context of all available treatment options.

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“…However, the patients often relapse and require multiple treatments, and may thus become refractory to re-treatment with PNAs. Fortunately, the recent introduction of novel agents has expanded the spectrum of therapy possibilities for those patients, and now, treatment options for the management of early-relapsed patients, or those refractory to PNAs, inlude IFN-α, rituximab and Moxe [19][20][21][22]. We reviewed the records from four patients treated at Copernicus Memorial Hospital, Lodz, Poland; all received multiple lines of 2-CdA and were subsequently treated with Moxe, followed by vemurafenib combined with rituximab.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, two patients were treated with IFN-α after relapse with 2-CdA: one of them did not respond and one obtained only a PR lasting 17 months. IFN-α may still have a place in the treatment, but its use is currently limited, being restricted to pregnant patients and in patients presenting with neutropenia below 0.2 × 109/L, when the risk of infection is high [20,21]. Our patients received Moxe within the pivotal, phase 3 multicenter study [11,12].…”

Section: Discussionmentioning

confidence: 99%

“…The history of the presented cases indicates that novel targeted agents and, in particular, vemurafenib plus rituximab, improve the prognosis of HCL patients, even those who are heavily pretreated with PNAs and Moxe. However, despite the interesting perspective of targeted treatments in HCL, older options should not be forgotten, including bendamustine plus rituximab [31] and (pegylated) interferon [20]. Still, HCL remains an incurable disease in such an advanced relapsed/refractory disease setting, and the development of novel therapeutic strategies is required.…”

Section: Discussionmentioning

confidence: 99%

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Vemurafenib and Rituximab in Patients with Hairy Cell Leukemia Previously Treated with Moxetumomab Pasudotox

Robak

Janus

Jamroziak

et al. 2021

JCM

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The purine nucleoside analogues cladribine and pentostatin are highly-active first-line therapeutic treatments for hairy cell leukemia (HCL), resulting in complete response rates of 80% to 90%. However, HCL patients continue to relapse, and sooner or later, most require subsequent lines of treatment. This report presents the cases of four relapsed patients with classic HCL who were treated with vemurafenib (mostly at the low dose of 240 mg twice daily for 16 weeks) combined with rituximab after the failure of several lines of therapy including cladribine with or without rituximab and moxetumomab pasudotox. Two patients achieved minimal residual disease negative complete response after combined treatment with vemurafenib and rituximab, with a hematologic response ongoing after 38 months from the end of treatment in one patient and a relapse of cytopenias occurring after 13 months in the other patient. A third patient normalized her blood counts and this hematologic response, which was not evaluated in the bone marrow at the end of treatment, was lost after 18 months. The last patient died due to infection and multi-organ failure, too early to verify response to vemurafenib. Two patients who had relapsed after vemurafenib and rituximab derived meaningful clinical benefit from retreatment with the same agents, but eventually relapsed again and started indefinite therapy with dabrafenib and trametinib leading to normalization of the blood counts (despite heavy bone marrow infiltration in the only patient so far evaluable in that regard). The outcomes of these cases indicate that novel targeted agents and, in particular, vemurafenib, combined with rituximab, improve the prognosis of HCL patients, even those heavily pretreated with PNAs and moxetumomab pasudotox.

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The current role of interferon in hairy cell leukaemia: clinical and molecular aspects

Cited by 10 publications

References 16 publications

Hairy Cell Leukemia Patients Have a Normal Life Expectancy—A 35-Year Single-Center Experience and Comparison with the General Population

Hairy Cell Leukemia Patients Have a Normal Life Expectancy—A 35-Year Single-Center Experience and Comparison with the General Population

How I treat refractory/relapsed hairy cell leukemia with BRAF inhibitors

Vemurafenib and Rituximab in Patients with Hairy Cell Leukemia Previously Treated with Moxetumomab Pasudotox

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