Patients with relapsed/refractory hairy‐cell leukemia

Paillassa, Jérôme; Troussard, Xavier

doi:10.1002/cnr2.1495

Cited by 14 publications

(12 citation statements)

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“…Patients relapsing after first-line treatment with PNAs in monotherapy are more difficult to treat and are at high risk to have a significant and impaired reduced OS. 66,75 No significant difference in terms of CR or relapse free survival (RFS) was observed between patients who remained on their initial PNA or those who switched treatments. 64,66 Patients treated in first-line with chemotherapy derive benefit from immuno-chemotherapy.…”

Section: Second Line Treatmentmentioning

confidence: 99%

“…In patients who relapse, therapeutic options will depend on the first‐line treatment and the duration of first remission. Patients relapsing after first‐line treatment with PNAs in monotherapy are more difficult to treat and are at high risk to have a significant and impaired reduced OS 66,75 . No significant difference in terms of CR or relapse free survival (RFS) was observed between patients who remained on their initial PNA or those who switched treatments 64,66 …”

Section: Update On Hcl Treatment and Hcl‐like Disordersmentioning

confidence: 99%

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Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

2021

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Disease Overview: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders characterized by the identification of hairy cells, a specific genetic profile, a different clinical course, and the need for appropriate treatment. Diagnosis: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation. Risk Stratification: Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood, and the immunoglobulin heavy chain variable region gene mutational status. VH4-34-positive HCL cases are associated with a poor prognosis. Treatment: Patients should be treated only if HCL is symptomatic. Chemotherapy with risk adapted therapy purine analogs (PNAs) are indicated in first-line HCL patients. The use of chemo-immunotherapy combining PNAs and rituximab (R) represents an increasingly used therapeutic approach. Management of relapsed/ refractory disease is based on the use of BRAF inhibitors (BRAFi) plus rituximab or MEK inhibitors (MEKi), recombinant immunoconjugates targeting CD22 or BrutonTyrosine Kinase inhibitors (BTKi). However, the optimal sequence of the different treatments remains to be determined. The Bcl2-inhibitors (Bcl-2i) can play a major role in the future. | INTRODUCTIONHairy cell leukemia (HCL) is recognized as an entity by the World Health Organization since 2008 1 and in the last 2017 revision of the WHO classification of lymphoid neoplasms. 2 HCL, four to five times more frequent in men than women, accounts for 2% of all leukemias with approximately 1.100 new HCL cases in the United States. 3 The few available population-based studies are limited. [4][5][6][7][8] When including HCL and HCL-like disorders, the overall age-adjusted to the 2000 US population incidence rate is 0.7 per 100 000 in men and 0.3/100 000 in women. When adjusting to the worldwide population, the incidence rate of HCL is 0.3 and 0.1/100 000, respectively, and remains relatively stable over time. 8 It is lower in non-Hispanic/black, Hispanic, or Asian/pacific Islander. Despite an improvement of overall (OS) and relative survival (RS), a significantly lower OS is observed among African American individuals compared with other ethnic groups. 6 The mortality rates for patients with HCL is similar to those of the general population 5 years after diagnosis. 9 HCL must be differentiated from other

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Section: Second Line Treatmentmentioning

confidence: 99%

Section: Update On Hcl Treatment and Hcl‐like Disordersmentioning

confidence: 99%

Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

2021

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“…La RC identifiée chez un patient a persisté plus d'un an [82]. Les RC sont observées de façon très fréquente dans les séries ultérieures avec un recul prolongé [83][84][85][86][87][88][89][90][91][92]. En France, le schéma habituel est une dose de 0, 14 mg/kg par jour par voie sous-cutanée pendant cinq jours.…”

Section: Traitement De Première Ligneunclassified

“…Malgré des réponses initiales durables, 40% des patients rechutent après un traitement de première ligne. Les patients à nouveau traités en monothérapie deviennent de moins en moins sensibles aux traitements et la durée de la réponse est de plus en plus courte [90,91]. L'intérêt de changer de PNA lors d'une rechute n'a pas été clairement démontré [85,87].…”

Section: Traitement De Première Ligneunclassified

Hairy Cell Leukemia and HCL-Like Disorders: Diagnosis and TreatmentLeuc閙ie �Tricholeucocytes et Autres Prolif閞ations �Cellules Chevelues: Diagnostic et Traitement

Maître¹,

Troussard²

2022

Oncologie

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La leucémie à tricholeucocytes (LT) représente 2% de l'ensemble des leucémies. Le diagnostic repose sur la présence dans le sang et/ou la moelle de tricholeucocytes: cellules lymphoïdes B au cytoplasme chevelu exprimant le CD103, CD123, CD11c et CD25. La mutation BRAF V600E , marqueur moléculaire de la maladie, est présente dans plus de 80% des cas. La LT doit être distinguée des autres syndromes lymphoprolifératifs chroniques B, notamment des autres proliférations à cellules chevelues, forme variante de la leucémie à tricholeucocytes (LT-V) et lymphome splénique diffus de la pulpe rouge (LSDPR). Des progrès thérapeutiques ont été récemment réalisés. Les analogues des purines (PNAs) en monothérapie: désoxycoformycine (DCF) ou 2-chloro-désoxyadénosine (CDA), restent le traitement de référence de la première ligne. Ils peuvent être associés aux anticorps monoclonaux anti-CD20 (rituximab, obinutuzumab) dès la première ligne, l'immunochimiothérapie permettant l'obtention de rémissions complètes (RC) prolongées. Chez les patients avec une maladie en rechute/réfractaire (R/R), de nouvelles options thérapeutiques ont émergé: immunotoxines, inhibiteurs de BRAF (BRAFi) ou de BTK. Ces traitements sont à discuter en réunion de concertation pluridisciplinaire (RCP). Chez les patients avec une LT-V, l'immunochimiothérapie est maintenant le traitement de référence en première ligne. Dans tous les cas, la surveillance hématologique prolongée est nécessaire, en raison du risque augmenté de cancer secondaire et notamment celui d'hémopathie maligne.

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“… 25 In relapsed/refractory (R/R) HCL patients, novel therapeutic approaches are needed in utilizing less-immunosuppressive drugs than PNAs. 26 In this review, we will focus on the interest of BTK inhibitors (BTKi) as a strategy in HCL and HCL-V.…”

Section: Introductionmentioning

confidence: 99%

Updates in hairy cell leukemia (HCL) and variant-type HCL (HCL-V): rationale for targeted treatments with a focus on ibrutinib

Paillassa

Safa

Troussard

2022

Therapeutic Advances in Hematology

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Hairy cell leukemia (HCL) and HCL-like disorders such as hairy cell leukemia variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL) are rare indolent B-cell malignancies. Purine analogs (PNAs), alone or in association with rituximab (R), are the standard of care for HCL in the first-line setting. However, PNAs are toxic and patients may become resistant to these drugs. Therefore, new therapeutic strategies are needed. Several recent in vitro studies highlighted the importance of the interactions between HCL cells and their microenvironment, in particular with bone marrow stromal cells, endothelial cells, and the extracellular matrix. In these interactions, chemokine receptors and adhesion molecules play a major role. Moreover, the importance of signaling pathways, like BRAF, BCR, and CXCR4 has been underlined. Bruton’s tyrosine kinase (BTK) is a fundamental signal transmitter of BCR and CXCR4 in HCL. Preclinical and recent clinical data showed an efficacy of ibrutinib, a BTK inhibitor (BTKi), in HCL and HCL-V. These promising results joined those of other emerging drugs like BRAF or MEK inhibitors and anti-CD22 immunotoxins. Plain Language Summary Bruton’s tyrosine kinase (BTK) inhibitors (BTKi) in hairy cell leukemia (HCL) and variant-type HCL The treatment of hairy cell leukemia (HCL) has changed significantly in recent years. In the first-line settings, treatment with purine analogs (PNAs) with or without anti-CD20 monoclonal antibodies remains the gold standard in 2022. In relapsed/refractory HCL, other drugs are needed: BRAF inhibitors: vemurafenib monotherapy with or without rituximab or dabrafenib in combination with trametinib, an MEK inhibitor (MEKi), as well as the anti-CD22 antibody drug conjugate moxetumomab pasudotox. There are arguments for the use of Bruton’s tyrosine kinase inhibitors (BTKi). Ibrutinib was recently tested in a multisite phase 2 study in 37 patients with either HCL (28 patients: 76%) or HCL-V (nine patients: 24%) including two who were previously untreated. Patients received single-agent ibrutinib at 420 mg daily (24 patients) or 840 mg daily (13 patients) until disease progression or unacceptable toxicity. The overall response rate (ORR) at 32 weeks was 24%, increasing to 36% at 48 weeks and reaching 54% at any time since starting ibrutinib. Seven patients achieved a complete response (CR) as the best response at any time on study, while 13 patients had a partial response (PR) and 10 patients had stable disease (SD). Interestingly, the response rate was not statistically different between HCL and HCL-V patients, suggesting that ibrutinib could be an option in both entities. The estimated 36-month progression-free survival (PFS) was 73% and the estimated 36-month overall survival (OS) was 85%, with no differences between HCL and HCL-V. The frequency of cardiovascular grade 1–2 adverse events (AEs) was 16% for atrial fibrillation; 3% for atrial flutter; 32% for hypertension; and 0%, 3%, and 11%, respectively, for grade ⩾ 3 AEs. Unlike in chronic lymphocytic leukemia (CLL), where the mechanism of action of ibrutinib is well known, the mechanism of action of ibrutinib in HCL appears to be unclear. No mutations were identified in patients with progressive disease, suggesting that the mechanisms of resistance could be different between HCL and CLL. The BTKi that are not yet approved are challenged by the new other targeted treatments.

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Patients with relapsed/refractory hairy‐cell leukemia

Cited by 14 publications

References 38 publications

Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

Hairy Cell Leukemia and HCL-Like Disorders: Diagnosis and TreatmentLeuc閙ie �Tricholeucocytes et Autres Prolif閞ations �Cellules Chevelues: Diagnostic et Traitement

Updates in hairy cell leukemia (HCL) and variant-type HCL (HCL-V): rationale for targeted treatments with a focus on ibrutinib

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