|The following article features coverage from the 2021 American Society of Hematology Annual Meeting. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
Fixed-duration ibrutinib plus venetoclax (Ibr+Ven) produced a higher rate of undetectable minimal residual disease (uMRD) compared with chlorambucil plus obinutuzumab (Clb+O) in elderly or unfit patients with previously untreated chronic lymphocytic leukemia (CLL), according to study results presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
Researchers presented further findings from the phase 3 GLOW trial. Previous results from the primary analysis showed that independent review committee (IRC)-assessed progression-free survival (PFS) was superior with Ibr+Ven.
The GLOW trial (ClinicalTrials.gov Identifier: NCT03462719) enrolled patients aged 65 years and older or 18 to 64 years with a Cumulative Illness Rating Scale score greater than 6 or creatinine clearance less than 70 mL/min. Participants were randomly assigned 1:1, stratified by IGHV and del(11q) status, to Ibr+Ven (3 cycles of ibrutinib lead-in, followed by 12 cycles of Ibr+Ven) or 6 cycles of Clb+O.
IRC-assessed PFS was the primary endpoint, and the rate of uMRD (<10-4) was a secondary endpoint. MRD samples were obtained for responders every 3 to 4 months in peripheral blood (PB) and at months 9 and 18 in bone marrow (BM) and were assessed with next-generation sequencing. PB/BM concordance was determined for patients with uMRD in PB at the end of treatment plus 3 months (EOT+3) who had a paired BM sample.
A total of 106 patients were randomly assigned to Ibr+Ven and 105 to Clb+O. Participants had a median age of 71.0 years, 51.7% had confirmed unmutated IGHV, 18.0% had del(11q), and 4.3% had a TP53 mutation. The median follow-up was 27.7 months (range, 1.7-33.8).
For MRD results at 10-4, the rate of uMRD was significantly higher in the Ibr+Ven group than in the Clb+O group in both BM (51.9% vs 17.1%; P <.0001) and PB (54.7% vs 39.0%; P =.0259). PB/BM uMRD concordance with Ibr+Ven was 92.9%.
In the Ibr+Ven arm, 27 of 41 patients (65.9%) with a complete response (CR) or CR with incomplete marrow recovery and 28 of 51 patients (54.9%) with a partial response achieved uMRD in BM. The rates in the Clb+O group were 33.3% (4/12) and 16.9% (13/77), respectively.
BM uMRD rates were higher for Ibr+Ven compared with Clb+O among participants with bulky disease (≥5 cm), del(11q), and unmutated IGHV. In the Ibr+Ven arm, BM uMRD was higher for unmutated IGHV (58.2%) vs mutated IGHV (44.4%).
For Ibr+Ven, 49 of 58 patients (84.5%) maintained PB uMRD from EOT+3 to EOT+12 vs 12 of 41 patients (29.3%) in the Clb+O group. In participants with detectable MRD after Ibr+Ven (30 patients), MRD levels remained stable for most patients from EOT+3 to EOT+12.
Regarding MRD results at 10-5, the rate of uMRD <10-5 was higher in the Ibr+Ven group than in the Clb+O group in BM (40.6% vs 7.6%), including patients with unmutated IGHV (45.5% vs 5.6%). In the Ibr+Ven group, PB/BM uMRD concordance at <10-5 was 90.9% (40/44 participants).
In patients with uMRD <10-4 in the Ibr+Ven group, a majority achieved <10-5 in PB (79.3%) and BM (78.2%), including those with unmutated IGHV. uMRD <10-5 in PB was largely sustained from EOT+3 to EOT+12 with Ibr+Ven (80.4% [37/46] of patients) but not with Clb+O (26.3% [5/19] of patients).
For PFS by MRD status at 10-4, in the Ibr+Ven arm, the PFS rate in the first 12 months after EOT was greater than 90% for patients with uMRD and for those who had detectable MRD. Participants in the Clb+O arm with detectable MRD in PB relapsed more quickly than those with uMRD. PFS trends were comparable according to MRD status in BM, and not all Ibr+Ven participants had 12 months of follow-up after EOT.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
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Munir T, Moreno C, Owen C, et al. First prospective data on minimal residual disease (MRD) outcomes after fixed-duration ibrutinib plus venetoclax (Ibr+Ven) versus chlorambucil plus obinutuzumab (Clb+O) for first-line treatment of CLL in elderly or unfit patients: the GLOW study. Presented at ASH 2021; December 11-14, 2021. Abstract 70.