ASH Highlights and Commentary: Chronic Lymphocytic Leukemia and Lymphomas

Abstract

125 Five-Year Analysis of MURANO Study Demonstrates Enduring Undetectable Minimal Residual Disease (uMRD) in a Subset of Relapsed/Refractory Chronic Lymphocytic Leukemia (R/R CLL) Patients (Pts) Following Fixed-Duration Venetoclax-Rituximab (VenR) Therapy (Tx) Arnon P. Kater, MD, PhD, Thomas J. Kipps, MD, PhD, Barbara Eichhorst, MD, Peter Hillmen, MBChB, PhD, FRCP, FRCPath, James D’Rozario, Carolyn Owen, MD, FRCPC, Sarit E Assouline, MD, MSc, Nicole Lamanna, MD, Tadeusz J. Robak, Javier de la Serna, Ulrich Jaeger, Guillaume Cartron, MD, PhD, Marco Montillo, Clemens Mellink, Brenda J. Chyla, Cameron Wilson, Jenny Wu, Yanwen Jiang, Marcus Lefebure, Michelle Boyer, and John F. Seymour Visit https://doi.org/10.1182/blood-2020-136109 for a complete list of contributor affiliations and full graphics. Introduction: The randomized Phase III MURANO study (NCT02005471) compared fixed-duration VenR with standard bendamustine-rituximab (BR) in R/R CLL. Deep responses with uMRD were associated with superior progression-free survival (PFS) of VenR vs BR with 48 months (mo) follow-up (f/u). We now report long-term MRD kinetics and updated efficacy outcomes, including re-exposure to VenR (to be presented), with a 5 year (yr) median follow-up (clinical cutoff date May 8, 2020). Methods: As published, pts were randomized to VenR (Ven 400 mg daily for 2 yrs + standard dose R for the first 6 mo) or B (70 mg/m2)R (6 mo). A sub-study was introduced in 2018, allowing pts who developed progressive disease (PD) following Tx with BR or VenR to receive the MURANO VenR regimen. PFS was based on investigator assessment. Peripheral blood MRD was analyzed centrally by allele-specific oligonucleotide polymerase chain reaction and/or flow cytometry. Pts were categorized by MRD status as previously reported, using <10-4 threshold for uMRD. MRD conversion was defined as 2 consecutive assays detecting MRD or PD in pts who previously had uMRD. Genomic complexity (GC) and del(17p) status were assessed by array comparative genomic hybridization. GC was defined as ≥3 copy number variations (CNV). All p-values are descriptive. Results: 389 pts were enrolled (VenR, n=194; BR, n=195). With a median f/u of 59.2 (range, 0-71.5) mo, the PFS benefit with VenR over BR was sustained (HR, 0.19 [95% CI: 0.15-0.26]; p<0.0001). Median PFS was 53.6 (95% CI: 48.4-57.0) mo for VenR and 17.0 (95% CI: 15.5-21.7) mo for BR. For pts who completed the full 2 yrs of Ven Tx (n=130), PFS estimates 36 mo post-end of treatment (EOT) were ~51.1% (95% CI: 40.2-61.9). Overall survival (OS) benefit was maintained for pts treated with VenR vs BR (HR, 0.40 [95% CI: 0.26-0.62]; p<0.0001), with 5-yr OS estimates of 82.1% (95% CI: 76.4-87.8) for VenR and 62.2% (95% CI: 54.8-69.6) for BR. Improved OS outcome was observed among the VenR pts that reached EOT without PD and had uMRD (83/118) compared with those with MRD (35/118), with 3-yr post-EOT survival estimates of 95.3% (95% CI: 90.0-100.0) vs 85.0% (95% CI: 72.8-97.2), respectively (Figure 1). Of the pts with uMRD at EOT, 32/83 had not shown PD and remained uMRD at the 5-yr update, 4/83 had PD without prior confirmed MRD conversion and 47/83 had MRD conversion. Median time to MRD conversion from EOT was 19.4 (95% CI: 8.7-28.3) J Adv Pract Oncol 2021;12(suppl 3):11-17 https://doi.org/10.6004/jadpro.2021.12.3.29 Th is ar tic le is dis tri bu te d u nd er th e t er m s o f t he Cr ea tiv e C om m on s A ttr ibu tio n N on -C om m er cia l N on -D er iva tiv e L ice ns e, wh ich pe rm its un re str ict ed no nco m m er cia l a nd no nde riv at ive us e, dis tri bu tio n, an d r ep ro du cti on in an y m ed ium , p rov ide d t he or igi na l w or k i s p ro pe rly ci te d.