Bosch, F. (Francesc)

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    Chromosome banding analysis and genomic microarrays are both useful but not equivalent methods for genomic complexity risk stratification in chronic lymphocytic leukemia patients
    (2022) Cuneo, A. (Antonio); Ramos-Campoy, S. (Silvia); Espinet, B. (Blanca); Oscier, D. (David); Blanco, M.L. (María Laura); Bea, S. (Silvia); Bougeon, S. (Sandrine); Baumann, T. (Tycho); Moreno, C. (Carolina); Bosch, F. (Francesc); Salgado, R. (Rocío); Puiggros, A. (Anna); Gimeno, E. (Eva); Nguyen-Khac, F. (Florence); Costa, D. (Dolors); Collado, R. (Rosa); Haferlach, C. (Claudia); Rigolin, G.M. (Gian Matteo); Calvo, X. (Xavier); Parker, H. (Helen); Larrayoz, M.J. (María J.); Schoumans, J. (Jacqueline); Strefford, J.C. (Jonathan C.); Calasanz-Abinzano, M.J. (Maria Jose); Ortega, M. (Margarita)
    Genome complexity has been associated with poor outcome in patients with chronic lymphocytic leukemia (CLL). Previous cooperative studies established five abnormalities as the cut-off that best predicts an adverse evolution by chromosome banding analysis (CBA) and genomic microarrays (GM). However, data comparing risk stratification by both methods are scarce. Herein, we assessed a cohort of 340 untreated CLL patients highly enriched in cases with complex karyotype (CK) (46.5%) with parallel CBA and GM studies. Abnormalities found by both techniques were compared. Prognostic stratification in three risk groups based on genomic complexity (0-2, 3- 4 and ¿5 abnormalities) was also analyzed. No significant differences in the percentage of patients in each group were detected, but only a moderate agreement was observed between methods when focusing on individual cases (kappa=0.507; P<0.001). Discordant classification was obtained in 100 patients (29.4%), including 3% classified in opposite risk groups. Most discrepancies were technique-dependent and no greater correlation in the number of abnormalities was achieved when different filtering strategies were applied for GM. Nonetheless, both methods showed a similar concordance index for prediction of time to first treatment (TTFT) (CBA: 0.67 vs. GM: 0.65) and overall survival (CBA: 0.55 vs. GM: 0.57).
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    Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma
    (2023) Li, C. (Chi-Chung); Assouline, S. (Sarit); Kwan, A. (Antonia); Budde, L.E. (Lucia E.); To, I. (Iris); Giri, P. (Pratyush); Huang, H. (Huang); Panizo, C. (Carlos); Schuster, S.J. ( Stephen J.); Sehn, L.H. (Laura H.); Flinn, I. (Ian); Peñuel, E. (Elicia); Bosch, F. (Francesc); Gregory, G.P. (Gareth P.); Fay, K. (Keith); Yin, S. (Shen); Matasar, M. (Matthew); Cheah, C. Y. ( Chan Y.); Yoon, S. (Sung-Soo); Johnston, A. (Anna); Yoon, D.H. (Dok Hyun); Shadman, M. (Mazyar); Bartlett, N.L. (Nancy L.); Wei, M.C. (Michael C.)
    As part of a phase 1 or 2 study, this single-arm expansion cohort established the efficacy and safety of mosunetuzumab monotherapy in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (received >= 2 previous lines of therapy). Intravenous mosunetuzumab was administered with cycle (C) 1 step-up dosing for cytokine release syndrome (CRS) mitigation: C1 day (D) 1: 1 mg; C1D8 2 mg; C1D15 and C2D1: 60 mg; C3 + D1: 30 mg. Hospitalization was not mandatory. Patients with complete response (CR) completed treatment after C8; those with partial response or stable disease continued treatment for a total of 17 cycles. The primary end point was CR rate (best response), assessed against a historical control CR rate (20%) by independent review facility. Eighty-eight patients (73.9% de novo DLBCL; 26.1% transformed follicular lymphoma) were enrolled; all had received previous anthracycline and anti-CD20 therapy. Overall response and CR rates were 42.0% (95% confidence interval [CI], 31.6-53.1) and 23.9% (95% CI, 15.4-34.1), respectively; CR rate did not reach statistical significance vs the historical control (P = .36). Median time to first response was 1.4 months. Median progression-free survival was 3.2 months (95% CI, 2.2-5.3). The CR rate in 26 patients who received previous chimeric antigen receptor T-cell (CAR-T) therapy was 12%. CRS was one of the most common adverse events (26.1% of patients); predominantly grade 1 to 2 and primarily in C1. Four patients (4.5%) discontinued mosunetuzumab owing to adverse events. Mosunetuzumab demonstrated notable efficacy and a manageable safety profile in patients with R/R DLBCL, including those previously treated with CAR-Ts. This trial was registered at www.clinicaltrials.gov as #NCT02500407.