Relapsed/refractory CLL following treatment with venetoclax + rituximab — What to do next?

At this year’s European School of Haematology (ESH) 2nd How to Diagnose and Treat: Lymphoma conference, the Lymphoma Hub was proud to host a virtual Satellite Symposium on the management and treatment of patients with relapsed/refractory (R/R) lymphoma.

Astrid Pavlovsky, Fundaleu, Buenos Aires, AR, and Francesc Bosch, University Hospital Vall d'Hebron, Barcelona, ES, discussed how they would treat a patient with chronic lymphocytic leukemia (CLL) who has relapsed after treatment with venetoclax + rituximab.

Patient case

Figure 1 illustrates the case of a patient with R/R CLL. The two speakers outline how they would move forward with this case, while presenting the latest data from relevant clinical trials in the R/R CLL setting.

Figure 1. R/R CLL patient case¹

BM, bone marrow; CLL, chronic lymphocytic leukemia; ECOG, FISH, fluorescence in situ hybridization; IGHV, immunoglobulin heavy chain variable region; R/R, relapsed and/or refractory; WBC, white blood cell.

Latin American perspective: Astrid Pavlovsky

Astrid Pavlovsky began with an overview of the ethnic composition of Latin America and the prevalence of common B-cell non-Hodgkin lymphoma types in Central and South America. She then highlighted the lack of targeted therapies and diagnostic techniques in some Latin American countries.

When discussing the patient case, she first eliminated cellular therapy as a feasible option due to the patient’s age and comorbidities, as well as the limited availability of experimental therapies in Latin America. As a result, Astrid Pavlovsky recommended therapeutic intervention with a pathway inhibitor (Figure 2), specifically a Bruton’s tyrosine kinase (BTK) inhibitor, and presented data from the ELEVATE CLL R/R study, which compared ibrutinib versus acalabrutinib for the treatment of high-risk CLL.

Figure 2. Schematic of treatment options following relapse to chemoimmunotherapy^2,3

Slide courtesy of Astrid Pavlovsky.

Watch Astrid Pavlovsky’s presentation below.

European perspective: Francesc Bosch

Francesc Bosch opened with a useful overview of the mechanisms of progression under venetoclax, and predictive biomarkers for prognosis following targeted therapy. In concordance with Astrid Pavlovsky, Bosch recommended transition to BTK inhibitor therapy for the selected patient case. He then highlighted the value of ibrutinib treatment in patients with R/R CLL previously treated with venetoclax in the MURANO study, which provided rationale for the proposed treatment strategy.

Bosch also discussed the potential benefit of treatment with Pi3K inhibitors and experimental chimeric antigen receptor (CAR) T-cell therapy in patients with R/R CLL who have received prior venetoclax.

Please take part in the survey and watch Francesc Bosch’s presentation below.

Conclusion

Presentations by Astrid Pavlovsky and Francesc Bosch at the virtual satellite symposium summarized a number of emerging agents that appear promising and feasible for treating patients with CLL who progress after treatment with venetoclax. The two talks highlighted the differences in the availability of novel agents between Latin America and Europe. However, the panelists came to the same conclusion that treatment with a BTK inhibitor is the best approach in handling the selected patient case.