CLL-487 First-Line Fixed-Duration Ibrutinib Plus Venetoclax (Ibr+Ven) vs Chlorambucil Plus Obinutuzumab (Clb+O): 55-Month Follow-Up From the GLOW Study

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 24; pp. S356 - S357
• Main Authors: Moreno, Carol, Munir, Talha, Owen, Carolyn, Follows, George, Hernández-Rivas, José-Ángel, Benjamini, Ohad, Janssens, Ann, Levin, Mark-David, Robak, Tadeusz, Simkovic, Martin, Voloshin, Sergey, Vorobyev, Vladimir, Yagci, Munci, Ysebaert, Loic, Qi, Qianya, Smith, Emma, Srinivasan, Srimathi, Schuier, Natasha, Baeten, Kurt, Bennett Caces, Donne, Niemann, Carsten, Kater, Arnon
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2024
• Subjects: chronic lymphocytic leukemia; CLL; fixed-duration regimen; ibrutinib; minimal residual disease (MRD); trial-in-progress; venetoclax; ibrutinib; trial-in-progress; minimal residual disease (MRD); CLL; fixed-duration regimen; chronic lymphocytic leukemia; venetoclax
• ISSN: 2152-2650
• DOI: 10.1016/S2152-2650(24)01286-2

In the GLOW trial (NCT03462719), fixed-duration Ibr+Ven vs Clb+O provided longer progression-free survival (PFS), overall survival (OS), and better undetectable minimal residual disease (uMRD) responses in patients with previously untreated chronic lymphocytic leukemia (CLL). To report outcomes from the long-term follow-up of GLOW. Adults aged ≥65 or 18-64 years with a Cumulative Illness Rating Scale score >6 or creatinine clearance <70 mL/min without del(17p)/TP53 mutations. Patients were randomly assigned (1:1) to Ibr+Ven (3 cycles [28 days] of Ibr, 12 cycles of Ibr+Ven) or Clb+O (6 cycles). Investigator-assessed PFS, OS, and uMRD (<10-4 by by-generation sequencing). With a median follow-up of 55 months, PFS was longer with Ibr+Ven (n=106) vs Clb+O (n=105) (hazard ratio [HR]=0.239, 95%CI, 0.159-0.359; P<0.0001); 54-month PFS rates were 65.8% and 19.1%, respectively. In patients treated with Ibr+Ven with unmutated IGHV (uIGHV; n=67) or mutated IGHV (mIGHV; n=32), 54-month PFS rates were 58% and 90%, respectively. PFS rates at 3 years post-treatment were 82% and 73%, respectively in patients with (n=58) or without (n=31) uMRD at 3 months after end of treatment (EOT+3). Among patients with uIGHV, PFS rates at 3 years post-treatment were 81% and 56%, respectively for patients with (n=40) or without (n=16) uMRD at EOT+3. In patients with mIGHV, PFS rates at 3 years post-treatment were ≥92% regardless of MRD status at EOT+3. At EOT+38, 32.1% of all Ibr+Ven–treated patients and 53.4% of patients with uMRD at EOT+3 achieved uMRD. The risk of needing second-line therapy was lower with first-line Ibr+Ven vs Clb+O (HR=0.174; 95%CI, 0.088-0.342; P<0.0001) among patients with uIGHV (HR=0.146; 95%CI, 0.069-0.310) or mIGHV (HR=0.708; 95%CI, 0.118-4.256). OS was better in the Ibr+Ven arm vs the Clb+O arm (HR=0.421; 95%CI, 0.237-0.747; P=0.0023); 54-month OS rates were 84.5% and 63.1%, respectively. Fixed-duration Ibr+Ven continued to show superior PFS and OS vs Clb+O. With Ibr+Ven, the PFS benefit was pronounced in patients with uIGHV with uMRD at EOT+3 and in patients with mIGHV regardless of MRD status at EOT+3. Janssen Scientific Affairs, LLC, a Johnson & Johnson company.