Title: HIGH EFFICACY OF VENETOCLAX PLUS OBINUTUZUMAB IN PATIENTS WITH COMPLEX KARYOTYPE (CKT) AND CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): A PROSPECTIVE ANALYSIS FROM THE CLL14 TRIAL
Abstract: Introduction: CKT (≥3 chromosomal aberrations) is associated with poor prognosis in CLL. In the CLL14 trial, treatment-naïve, elderly, unfit CLL patients (pts) received chlorambucil plus obinutuzumab (ClbG, n=216) or venetoclax plus obinutuzumab (VenG, n=216) for 12 cycles. After median follow-up of 29 months (mo), longer progression-free survival (PFS), and higher overall response rate (ORR) and rate of minimal residual disease (MRD) negativity were seen with VenG vs ClbG. Here, we present a prospective evaluation of CKT in CLL pts treated with a fixed-duration, chemotherapy-free regimen of VenG. Methods: Metaphase spreads were produced after IL-2/CpG-stimulation and analyzed according to ISCN 2013. ORR, PFS, overall survival (OS) and MRD rates were evaluated according to presence of CKT alone and in combination with TP53aberrations. PFS and OS were estimated using the Kaplan–Meier method. Survival times were compared using non-stratified log-rank tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression modelling. Results: Chromosome analysis was performed successfully in 397/432 (92%) randomized pts. CKT and non-CKT (NCKT) were found in 34 (17%) and 166 (83%) VenG pts, respectively, and 30 (15%) and 167 (85%) ClbG pts, respectively. Del(17p)/TP53mut was detected in 11/34 (32%) VenG CKT pts and in 9/29 (31%) ClbG CKT pts. Most pts with CKT were graded as high or very high risk according to the CLL-International Prognostic Index (CLL-IPI; 79% and 82%, respectively). In the VenG arm, ORR was 82% in CKT and 87% in NCKT pts; MRD negativity rate 3 mo after treatment completion in peripheral blood (PB) was 79% vs 77%, respectively, and in bone marrow (BM) 59% and 58%, respectively. No difference in PFS (Figure 1) or OS was seen between CKT and NCKT pts (median not reached [NR]; HR 1.909 [95% CI 0.806–4.520] and HR 1.511 [95% CI 0.496–4.600], respectively). For ClbG, ORR was 50% in CKT and 78% in NCKT pts; MRD negativity rate was lower in CKT vs NCKT pts, in PB (20% vs 40%, respectively) and BM (0% vs 22%, respectively). Median PFS was 19 mo in ClbG CKT pts and NR in NCKT pts (HR 2.790 [95% CI 1.631–4.772], p<0.001). OS was significantly shorter in CKT vs NCKT pts (median NR; HR 3.736 [95% CI 1.357–10.287], p=0.006). In CKT pts, presence of del(17p)/TP53mut did not significantly alter PFS compared with pts without del(17p)/TP53mut in the VenG (HR 1.419 [95% CI 0.317–6.353]) or ClbG groups (HR 2.103 [95% CI 0.795–5.567]). Funding: This study was funded by F. Hoffmann-La Roche Ltd and Abbvie Inc. Third-party editing and administrative support was provided by Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd. This abstract has been previously submitted to EHA 2019. Keywords: chronic lymphocytic leukemia (CLL); obinutuzumab; venetoclax. Disclosures: Al-Sawaf, O: Other Remuneration: AbbVie, Roche, Gilead, Janssen. Bahlo, J: Honoraria: Roche; Other Remuneration: Expenses: Roche. Fink, A: Consultant Advisory Role: Janssen Pharamceutical. Tandon, M: Employment Leadership Position: Roche. Humphrey, K: Employment Leadership Position: Roche; Stock Ownership: Roche. Jiang, Y: Employment Leadership Position: Genentech; Stock Ownership: Genentech. Schary, W: Employment Leadership Position: AbbVie; Stock Ownership: AbbVie. Porro Lurà, M: Employment Leadership Position: F. Hoffmann - La Roche Ltd; Stock Ownership: F. Hoffmann - La Roche Ltd. Ritgen, M: Consultant Advisory Role: Roche, Abbvie; Research Funding: Roche, Abbvie; Other Remuneration: Personal Fees: Roche. Tausch, E: Consultant Advisory Role: Roche; Other Remuneration: Speakers’ Bureau: Roche; Expert Testimony: Abbvie; Expenses: Abbvie. Stilgenbauer, S: Research Funding: AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann La-Roche, Janssen, Novartis, Pharmacyclics, Sunesis; Other Remuneration: Personal Fees: AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann La-Roche, Janssen, Novartis, Pharmacyclics, Sunesis. Eichhorst, B: Consultant Advisory Role: Abbvie, Roche; Honoraria: Abbvie, Roche; Research Funding: Abbvie, Roche; Other Remuneration: Speakers’ Bureau: Abbvie, Roche; Expenses: Abbvie, Roche. Fischer, K: Other Remuneration: Expenses: Roche. Hallek, M: Consultant Advisory Role: Roche, Abbvie; Honoraria: Roche, Abbvie, Gilead, Janssen, Celgene, Boehringer Ingelheim; Research Funding: Roche, Abbvie; Other Remuneration: Speakers’ Bureau: Roche, Abbvie. Kreuzer, K: Consultant Advisory Role: Roche, Abbvie; Other Remuneration: Expert Testimony: Roche, Abbvie.
Publication Year: 2019
Publication Date: 2019-06-01
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 1
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