New Greek consensus statement for the treatment of chronic lymphocytic leukemia

[CLLerinOz]

There is now a new consensus statement for the treatment of CLL in Greece. The statement was published on 1 March 2025 and provides treatment recommendations for both first-line and relapsed refractory CLL.

"Abstract. Background: New targeted therapies have revolutionized the treatment landscape in CLL. Biological features, patient characteristics and preferences and the safety profile of each treatment option should be taken into consideration for making the optimal treatment choice. This consensus practice statement on CLL treatment was developed by a group of Greek experts in CLL based on the available evidence for both first-line treatment and the relapsed/refractory setting." (my emphasis)

In the first-line setting, the Greek statement provides advice based on TP53 aberration and on IGHV status (see Fig. 1 in the full statement).

"Recommendations for CLL patients with TP53 aberrations. - More prolonged disease control achieved with BTKis appears to confer greater benefit to patients with TP53 aberrations compared to other treatments. - Fixed-duration treatment with the Ven-Obi combination does not appear to overcome the negative prognostic impact of TP53 aberrations. - CIT is not recommended."

"Recommendations for M-CLL patients 1. Time-limited treatment options with novel agents are the preferred therapy (Ven-Obi, Ibr-Ven) 2. CIT such as FCR should only be considered for fit and younger patients if targeted therapies are not accessible."

"Recommendations: 1. Targeted therapies are preferred for patients with U-CLL over CIT. 2. Cardiotoxicity is a class effect of BTKis, and alternative treatment options should be considered for patients at increased cardiac risk. 3. Among BTKis, Acalabrutinib and Zanubrutinib show a favorable safety profile compared to Ibrutinib."

"The role of anti-CD20 in the context of continuous treatment. No significant difference was seen in terms of PFS between Ibrutinib monotherapy and Ibrutinib - Rituximab in the ALLIANCE trial.¹⁵ In the ELEVATE TN trial, at 6 years of follow-up, PFS was significantly longer in patients treated with Acalabrutinib plus Obinutuzumab versus Acalabrutinib, while median OS was not reached in any treatment arm and was considerably longer in patients treated with Acalabrutinib-Obinutuzumab versus Obinutuzumab-Chlorambucil combination.¹⁸ However, patients in the Acalabrutinib-Obinutuzumab arm experienced more frequently grade ≥3 adverse events, such as neutropenia and thrombocytopenia.¹⁸ Another important issue concerning the addition of Obinutuzumab to Acalabrutinib concerns the increased vulnerability of patients with CLL receiving anti-CD20 antibodies to severe coronavirus disease 2019 (COVID-19) as well as their impaired immune response to vaccination against COVID-19.³⁴ "

In the relapsed/refractory setting, it categorises patients according to their TP53 status and previous treatment history eg whether or not they've had chemoimmunotherapy, BTKi or venetoclax based therapy. (see Fig.2 in the full statement)

"Management of relapsed/refractory CLL (Figure 2). Crucial issues for deciding on treatment of relapsed/refractory(R/R) CLL are the type of first-line treatment and the duration of response after first-line treatment. TP53 aberrations remain the most important"

Like the statement prepared for those in the Gulf region which was also published recently healthunlocked.com/cllsuppo... , it provides evidence from relevant clinical trials.

Sachanas S, Vassilakopoulos T, Angelopoulou M, Papageorgiou S, Spanoudakis E, Bouzani M, Dimou M, Panagiotidis P. Greek Consensus on Chronic Lymphocytic Leukemia (CLL) Treatment. Mediterr J Hematol Infect Dis. 2025 Mar 1;17(1):e2025014. doi: 10.4084/MJHID.2025.014. PMID: 40084092; PMCID: PMC11906138.

mjhid.org/mjhid/article/vie...

I anticipate that we'll see more regional statements like these ones as countries move beyond the era of chemoimmunotherapy for first-line CLL.

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CLLerinOz

[Smakwater]

Optimal care needs to be available to all. It is a good sign to see countries like Greece advancing in medical technology and practice.

JM