VENETOCLAX IN MULTI-RELAPSED MANTLE CELL LYMPHOMA PATIENTS: A REAL-LIFE MULTICENTRIC EXPERIENCE

Background:Mantle cell lymphoma (MCL) is a very heterogeneous disease, ranging from indolent forms - candidates to the “watch & wait” strategy – to the aggressive ones - that need an intensive treatment. Re- cently, ibrutinib and venetoclax, alone or in combination, have been re- ported to be effective in relapsed patients, with overall response rate (ORR) of 40-50%, and median progression-free-survival (PFS) ranging from 3.2 to 8 months. Aim:to describe the clinical outcomes of 12 multiply relapsed MCL patients (10 in fourth-fifth line of therapy) who received venetoclax (10 cases) or venetoclax in combination with ibrutinib (2 cases) in the vene- toclax compassionate use in 8 Italian centers. Ten patients already re- ceived ibrutinib, 25% had blastoid histology and 80% presented with a poor performance status. Results: Median follow-up from diagnosis was 7 years; at the time of venetoclax treatment all patients failed the previous therapy. Median WBC value was 8.8x109/L, median Hb 11.3 and median PLT count 164.7x109/L. Seven patients, after ramp-up, received a full dose of 800 mg; the median duration of treatment was 5 months (range, 1-15). Sig- nificant adverse events were observed in 7/12 cases, but only 2 patients discontinued therapy for hematological toxicity: comparison of WBC, Hb and PLT values before and after venetoclax showed a significant de- crease of PLT only, with stable WBC and Hb levels. The extra-hemato- logical adverse events included gastro-intestinal toxicity and one case of tumor lysis syndrome. Two patients are still receiving venetoclax after more than 30 months; 4 patients underwent allogeneic transplantation and other 4 received a further treatment after venetoclax discontinuation. ORR was 50%; 9 patients had progressed and 5 died; median overall and progression-free post-venetoclax survivals were 8 and 6 months, respec- tively, and they were not conditioned by sex, age or blastoid histology. Conclusions: our real-life multicenter experience, even if still limited, is perfectly in line with data from literature, both for ORR and duration of response (50%vs42-50%; 5vs4 months). Notwithstanding our pa- tients were heavily pre-treated and ibrutinib resistant, survival was sat- isfying and venetoclax functioned as bridge to transplant in 4 cases. Toxicity also had a low impact, with thrombocytopenia being the most frequent adverse event, making venetoclax an attracting therapy for re- lapsed MCL patients.