Αρχική World News BRAF Inhibitor and Rituximab for the Management of Refractory or Relapsed HCL

BRAF Inhibitor and Rituximab for the Management of Refractory or Relapsed HCL

In a phase II, single-centre, academic study involving patients with hairy-cell leukaemia (HCL), a chemotherapy-free regimen of BRAF inhibitor, vemurafenib and the anti-CD20 monoclonal antibody, rituximab was active in patients in whom treatment with purine analogues had failed. Italian researchers from the Ospedale S. Maria della Misericordia in Perugia, who published their findings on 13 May 2021 in The New England Journal of Medicine, wrote that addition of rituximab to vemurafenib led to a complete response (CR) in 87% of the patients and 78% were progression-free at 3 years. Owing to the absence of myelotoxic effects, this combination may also be helpful as a definitive treatment in the context in which highly immunosuppressive chemotherapy is contraindicated, such as in patients who have active infections or are at risk for COVID-19.

The authors wrote in the study background that HCL is a CD20-positive, indolent, mature B-cell neoplasm that is highly responsive to the purine analogues cladribine and pentostatin. However, up to 58% of the patients with HCL have a relapse, with the disease becoming progressively less sensitive to purine analogues, which also cause cumulative haematologic and immunologic side effects. Therefore, for patients with refractory or relapsed HCL, non-myelosuppressive therapies that provide a durable CR, including the eradication of minimal residual disease (MRD), are needed.

In HCL, a BRAF V600E kinase–activating mutation plays a pathogenetic role. In clinical studies involving patients with refractory or relapsed HCL, BRAF V600E targeting with vemurafenib led to a response in 91% of the patients, of whom 35% had CR. However, the median relapse-free survival (RFS) was only 9 months after treatment was stopped.

Vemurafenib-resistant leukaemic cells retain strong CD20 expression, which is a potential target for rituximab. Rituximab frequently induces responses, but induces few complete remissions in patients with refractory or relapsed HCL. Because rituximab is non-myelotoxic and may complement intracellular BRAF inhibition in killing leukaemic cells, the study team performed this phase II clinical study of adding rituximab to vemurafenib in an effort to improve the depth and duration of response in patients with refractory or relapsed HCL. The primary endpoint was CR at the end of planned treatment.

Among the 30 enrolled patients with HCL, the median number of previous therapies was 3. A CR was observed in 26 patients (87%) in the intention-to-treat population. All the patients who had HCL that had been refractory to chemotherapy (10 patients) or rituximab (5 patients) and all those who had previously been treated with BRAF inhibitors (7 patients) had CR.

Thrombocytopenia resolved after a median of 2 weeks, and neutropenia after a median of 4 weeks.

Of the 26 patients with a CR, 17 (65%) were cleared of MRD. Progression-free survival among all 30 patients was 78% at a median follow-up of 37 months. The RFS among the 26 patients with a response was 85% at a median follow-up of 34 months. In post hoc analyses, MRD negativity and no previous BRAF inhibitor treatment correlated with longer RFS.

Side effects, mostly of grade 1 or 2, were those that had previously been observed for these agents.

The authors concluded that in their small study, a chemotherapy-free, non-myelotoxic regimen of vemurafenib and rituximab was associated with a durable CR in most patients with refractory or relapsed HCL. Randomised comparison of combination of vemurafenib and rituximab is warranted against the chemotherapy-based standard of care in the context of first-line treatment to assess whether similar efficacy can be obtained with less side effects.

The grants were reported from the European Research Council, Associazione Italiana per la Ricerca sul Cancro, Leukemia and Lymphoma Society, Hairy Cell Leukemia Foundation, Ministero della Salute, and the Fondation ARC pour la Recherche sur le Cancer.


Tiacci E, De Carolis L, Simonetti E, et al. Vemurafenib plus Rituximab in Refractory or Relapsed Hairy-Cell Leukemia. N Engl J Med 2021;384:1810-1823. DOI: 10.1056/NEJMoa2031298.


Προηγούμενο άρθρο‘Hamilton’ Star Who Battled Breast Cancer is Giving Back to Current Patients
Επόμενο άρθροPeace


Συμπληρώστε το email σας για να λαμβάνετε τις σημαντικότερες ειδήσεις από το ogkologos.com

Βρείτε μας

2,449ΥποστηρικτέςΚάντε Like

Διαβαστε Επίσης

Καρκίνος και Κορωνοϊός (COVID-19) ΜΕΡΟΣ Α

Εάν είστε καρκινοπαθής, το ανοσοποιητικό σας σύστημα μπορεί να μην είναι τόσο ισχυρό όσο κανονικά, έτσι μπορεί να ανησυχείτε για τους κινδύνους που σχετίζονται...


Η Παγκόσμια Ημέρα Κατά του Καρκίνου καθιερώθηκε με πρωτοβουλία της Διεθνούς Ένωσης κατά του Καρκίνου (UICC), που εκπροσωπεί 800 οργανώσεις σε 155 χώρες του...


ΕΞΕΛΙΞΕΙΣ ΣΤΗ ΘΕΡΑΠΕΙΑ ΤΟΥ ΜΗ-ΜΙΚΡΟΚΥΤΤΑΡΙΚΟΥ ΚΑΡΚΙΝΟΥ ΤΟΥ ΠΝΕΥΜΟΝΑ (ΜΜΚΠ) Γράφει ο Δρ Παπαδούρης Σάββας, Παθόλογος-Ογκολόγος   Ο ΜΜΚΠ βρίσκεται αναλογικά στο 80% και πλέον του συνολικού...

Διατρέχουν όντως οι καρκινοπαθείς μεγαλύτερο κίνδυνο λόγω κοροναϊού;

Σε πρακτικό επίπεδο, τα δεδομένα των σχετικών μελετών υποδηλώνουν ότι η χημειοθεραπεία ή οι άλλες αντι-νεοπλασματικές θεραπείες δεν αυξάνουν σημαντικά τον κίνδυνο θνησιμότητας από...

FDA: Η ακτινοβολία των smartphones δεν προκαλεί καρκίνο

Σε μια νέα έκθεσή της, η Υπηρεσία Τροφίμων και Φαρμάκων (FDA) των ΗΠΑ αναφέρει ότι επανεξέτασε τις σχετικές επιστημονικές έρευνες που δημοσιεύθηκαν τα τελευταία...

Νέα ανακάλυψη, νέα ελπίδα για τον καρκίνο

Ένα νεοανακαλυφθέν τμήμα του ανοσοποιητικού μας συστήματος θα μπορούσε να αξιοποιηθεί για την αντιμετώπιση όλων των ειδών καρκίνου, σύμφωνα με επιστήμονες του πανεπιστημίου Cardiff...
- Advertisment -

Ροή Ειδήσεων

Making the most of your ‘eureka’ moment: getting from the science to the clinic

How can we make the vital journey from research to clinical impact more efficient? It all comes down to empowering researchers to develop an...

Black Women Have Nearly Three Times the Risk of Developing Triple Negative Breast Cancer, Study Says

Triple-negative breast cancer is notoriously hard to treat and tends to be more aggressive. It’s also more common among Black women. A new study...

Pioneer in Autism Diagnosis And Treatment Dies At 97

The community is mourning the loss of a true pioneer in autism diagnosis and treatment who strongly advocated for education for people with autism. Dr....

A Novel Combination of Cabozantinib Plus Atezolizumab Demonstrates Encouraging Activity and Acceptable Tolerability in Advanced RCC

In the COSMIC-021 study, cabozantinib plus atezolizumab demonstrated encouraging clinical activity in patients with advanced renal cell carcinoma (RCC). Robust clinical activity was observed...

A celebration of peer review

Peer review is an incredibly important part of how we maintain the excellence of the research we fund. As part of Peer Review Week,...

People with Intellectual Disability at Increased Risk of Cancer

People with intellectual disability are at an increased risk of any cancer, as well as several specific cancer types. The findings from a population-based...