Venetoclax-Obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the phase 3 CLL14 study.
Othman Al-SawafSandra RobrechtCan ZhangStefano OlivieriYi Meng ChangAnna-Maria FinkEugen TauschChristof SchneiderMatthias RitgenKarl-Anton KreuzerLiliya SivchevaCarsten Utoft NiemannAnthony P SchwarerJavier LoscertalesRobert WeinkoveDirk StrumbergAllanah KilfoyleBeenish S ManzoorDureshahwar JawaidNnadozie EmechebeJacob DevineMichelle BoyerEva D RunkelBarbara EichhorstStephan StilgenbauerYanwen JiangMichael J HallekKirsten FischerPublished in: Blood (2024)
Venetoclax-obinutuzumab (Ven-Obi) is a standard-of-care for patients with previously untreated chronic lymphocytic leukemia (CLL). In the CLL14 study, patients with previously untreated CLL and coexisting conditions were randomized to 12 cycles of Ven-Obi (n=216) or chlorambucil-obinutuzumab (Clb-Obi, n=216). Progression-free survival (PFS) was the primary endpoint. Key secondary endpoints included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS) and rates of adverse events. Patient reported outcomes (PROs) of time until definitive deterioration (TUDD) in quality of life (QoL) were analyzed. At a median observation time of 76.4 months, PFS remained superior for Ven-Obi compared to Clb-Obi (median 76.2 vs 36.4 months; HR 0.40[95%CI 0.31-0.52], p<0.0001). Likewise, TTNT was longer after Ven-Obi (6-year-TTNT 65.2% vs 37.1%; HR 0.44, 95%CI 0.33-0.58, p<0.0001). In the Ven-Obi arm, presence of del(17p), unmutated-IGHV and lymph node size ≥5 cm were independent prognostic factors for shorter PFS. Five years after treatment, 17 patients (7.9% of intention-to-treat-population) in the Ven-Obi arm had uMRD (<10-4 in peripheral blood) compared to 4 (1.9%) in the Clb-Obi arm. 6-year-OS rate was 78.7% in the Ven-Obi and 69.2% in the Clb-Obi arm (HR 0.69[95%CI 0.48-1.01], p=0.052). A significantly longer TUDD in global health status/QoL was observed in the Ven-Obi compared to the Clb-Obi arm (median 82.1 vs 65.1 months; HR 0.70[95%CI 0.51-0.97]). Follow-up adjusted SPM incidence rates were 2.3 and 1.4/1000 patient-months in the Ven-Obi and Clb-Obi arm, respectively. The sustained long-term survival, uMRD and QoL benefits support the use of one-year fixed-duration Ven-Obi in CLL. NCT02242942, EudraCT 2014-001810-24.
Keyphrases
- chronic lymphocytic leukemia
- prognostic factors
- patient reported outcomes
- lymph node
- peripheral blood
- free survival
- end stage renal disease
- chronic kidney disease
- clinical trial
- squamous cell carcinoma
- randomized controlled trial
- neoadjuvant chemotherapy
- case report
- ejection fraction
- chronic pain
- peritoneal dialysis
- quality improvement
- study protocol
- smoking cessation
- patient reported