F. Massaro MD

Highlights in indolent lymphomas and chronic lymphocytic leukaemia

SUMMARY

In this edition, we received significant updates regarding the first-line chemo-free management of follicular lymphoma (FL) and Waldenström macroglobulinaemia (WM). For the treatment of relapsed/refractory (R/R) FL, new data on the use of combinations involving novel monoclonal antibodies (mAbs) and bispecific antibodies (BITEs) aim to reshape the current therapeutic landscape. These approaches challenge the widely used combination of rituximab and lenalidomide, as proposed in the AUGMENT trial, which remains a prominent option in this setting.¹ Additionally, long-term follow-up data on the use of CAR-T in FL seem to support their curative potential, even in the setting of indolent lymphomas. In first-line CLL, new combinations of checkpoint inhibitors, covalent (cBTKi) and non-covalent BTK inhibitors (ncBTKi) with venetoclax and obinutuzumab show impressive efficacy and disease control. For R/R CLL, significant updates on the use of BITEs and BTK degraders highlight promising new therapeutic options, particularly addressing the unmet needs in managing double-refractory patients (cBTKi and BCL-2 inhibitors). Finally, the TRANSCEND CLL 004 trial presented impressive efficacy and safety results with the combination of CAR-T and cBTKi.

(BELG J HEMATOL 2025;16(1):7–11)

Highlights in indolent lymphomas and chronic lymphocytic leukaemia

SUMMARY

Several abstracts highlighted the efficacy of bispecific antibodies (BITEs) in the treatment of follicular lymphoma (FL), with interesting preliminary results in first line of treatment, both as monotherapy and combined with other agents. In the relapse/refractory (R/R) setting, robust and durable efficacy was shown for CAR-T particularly in the 3-year follow-up update of the ELARA trial. In first line CLL, an MRD-driven approach seems feasible and beneficial according to the results of the FLAIR trial. The update of the GLOW and the GAIA trials disclosed important information to identify the ideal molecular subgroup for each treatment combination. Finally, in the R/R setting, encouraging data from the use of non-covalent BTK inhibitor (ncBTKi) pirtobrutinib and CAR-T product lisocabtagene maraleucel (liso-cel) even in the poor prognosis group of patients exposed to both a covalent BTKi (cBTKi) and a BCL2 inhibitor (BCL2i).

(BELG J HEMATOL 2024;15(1):18–21)

Highlights from the 20^th iwCLL

SUMMARY

The 20^th edition of the international workshop on Chronic Lymphocytic Leukaemia (iwCLL) in Boston showcased significant progress in the management of CLL. In this summary we highlight key findings and emerging insights from the conference.

• Supportive care: infection still represent a significant threat for CLL patients, focusing on prevention remains crucial. Major role for vaccination and immunoglobulins replacement.
• First line treatment: advances in first line CLL treatment have expanded options beyond chemoimmunotherapy. Continuous treatment with covalent BTK inhibitors (cBTKi) as well as fixed-duration treatment such as Obinutuzumab-Venetoclax are effective options for fit and unfit patients.
• Minimal residual disease (MRD): MRD is a strong predictor of prolonged PFS and OS in CLL. However, the relevance of MRD kinetic and its connection to treatment response varies according to the scheme. New techniques considering also the nodal compartment are needed.
• Relapse and emerging therapies: resistance mechanisms and emerging drugs to address double-refractory CLL patients have been explored. New BCL-2 inhibitors, non-covalent BTK inhibitors (ncBTKi) and BTK degraders are the most promising agents. CAR-T cell therapy and bispecific antibodies (BiTEs) also show an interesting preliminary activity in this setting.
• Richter transformation (RT): RT is associated to a wide genetic heterogeneity and poor outcome. New treatments and particularly CAR-T and BiTEs seem promising in this setting.

(BELG J HEMATOL 2023;14(8):347–50)

Rational approach of older patients with chronic lymphocytic leukaemia

SUMMARY

The majority of CLL patients are elderly, with a median age of those requiring a first line treatment, close to 76 years old. Nowadays, multiple treatment options are available for this disease, ranging from chemo immunotherapy regimens to biological therapies. The treatment decision in an older CLL patient is a four-step procedure, starting firstly with the assessment of treatment criteria. The second step is to evaluate the life-expectancy of the patient, its autonomy, vulnerabilities and the socio-economic status. The subsequent step is to define treatment options according to prognostic factors. Last, but not least, the patient should be involved in the final decision to know to what extend he is willing to receive a treatment with a potential curative or palliative intent. The assessment of an elderly CLL patient is a complex procedure, not only comprehending the evaluation of biological and hematological parameters but also clinical, social and psychological features, which equally contribute to the selection of the most valuable strategy.

(BELG J HEMATOL 2021;12(4):147-54)