Skip to main content
iwCLL 2023 Main banner
Final Program


iwCLL X / Twitter
Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.
Back
View ePoster

Category: General Abstract

1205 - Rituximab Maintenance after Chemoimmunotherapy Induction in 1st and 2nd Line Improves Progression Free Survival: Long Term Follow up of the International Randomized AGMT-CLL8/a Mabtenance Trial

Introduction: Results of Rituximab maintenance after chemoimmunotherapy induction in 1st or 2nd line for 263 patients from the AGMT-CLL8/a Mabtenance trial NCT01118234 (Lancet Haematol. 2016) had been previously presented with a median follow up (FU) of 33.4 months and had shown a PFS benefit. We present an updated FU of 87.3 months, including analyses of MRD endpoints and salvage treatment results.

Results: The primary endpoint PFS benefit of maintenance remained stable and significant over time with an increase in median PFS from 35.6 to 47.5 months in the maintenance population compared to observation (p=0.012). PFS at median FU was 31.1% vs 20.2% in maintenance vs observation patients, respectively. The median time to next treatment increased from 53.3 in the observation arm to 78.7 months in the maintenance arm (p=0.01). The trial was not powered for analysis of OS. We observed no significant benefit in OS with 62.6% in the observation arm vs 68.4% in the maintenance arm alive at the median FU (p=0.24).
In exploratory analyses MRD parameters (MRD from PB or BM, quantitative MRD subgroups) and BMI (as previously published) remained significant predictors of PFS with longer FU. The effect of rituximab maintenance was more pronounced in patients with detectable MRD after induction. MRD-parameters were also highly significant predictors of OS. A novel parameter of dynamic assessment of MRD in the first 6 months of observation (or maintenance) was a predictor of PFS independent of MRD strata.
An analysis of retreatment outcomes in 144 retreated patients to date showed that the inclusion of novel drugs (any BTKi, Venetoclax or PI3K) in retreatment at any time (n=85 or 59% of retreated patients) led to a highly significant increase in OS (p < 0.0001) for the group salvaged with novel drugs in any line of salvage. Patients in the maintenance arm had a somewhat higher percentage of novel drug treatment (66% vs 53% in the observation arm) – likely due to the 25.4 months longer time to next treatment in a sensitive period for access to the novel drugs. Despite this small, but observable difference in usage of or access to novel drugs, no significant OS benefit was observed for maintained patients, likely because a majority of retreated patients had received novel drugs in both arms.

Conclusions: We present longer FU of a trial of rituximab maintenance after remission induction in the chemoimmunetherapy era. With longer FU we observe stable and meaningful benefits for maintenance in PFS and TTNT. We can validate MRD endpoints for PFS and OS prediction in long follow up and show novel dynamic MRD endpoints. Finally, we observe an enormous increase in OS for the trial group receiving novel drugs in any line of salvage, suggesting that OS benefits may no longer be attainable in trials due to effective salvage options in the current treatment paradigms.

    Primary Author; Presenting Author(s)

  • AE

    Alexander Egle, MD

    Professor
    3rd Medical Dept. with Hematology, Medical Oncology, Rheumatology and Infectiology, Paracelsus Medical University
    Salzburg, Salzburg, Austria

    • Co-Author(s)

  • PO

    Petra Obrtlíková, MD

    First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague
    Prague, Czech Republic

  • Lukáš Smolej, MD, PhD

    Professor
    4th Department of Internal Medicine – Hematology, University Hospital and Charles University Faculty of Medicine in Hradec Králové
    Hradec Králové, Kralovehradecky kraj, Czech Republic

  • TK

    Tomáš Kozák, MD

    Department of Internal Medicine-Hematology, Univ Hospital Kralovske Vinohrady
    Prague, Czech Republic

  • JB

    Jan-Paul Bohn, MD, PhD

    Department of Internal Medicine V, Medical University Innsbruck
    Innsbruck, Tirol, Austria

  • JA

    Johannes Andel, MD

    Department of Internal Medicine II, Pyrn-Eisenwurzen Klinikum Steyr
    Steyr, Oberosterreich, Austria

  • JT

    Josef Thaler, MD

    Professor
    4th Medical Dept. of Internal Medicine, Hematology, Internistic Oncology and Palliative Medicine, Klinikum Wels-Grieskirchen GmbH
    Wels, Oberosterreich, Austria

  • EM

    Eva Mikušková, MD

    Department of Hematooncology 2, National Cancer Institute
    Bratislava, Slovakia

  • LG

    Liana Gercheva, MD

    Professor
    Clinic of Hematology, University Hospital St Marina
    Varna, Bulgaria

  • TN

    Thomas Nösslinger, MD

    3rd Medical Department for Haematology and Oncology, Hanusch Hospital
    Vienna, Wien, Austria

  • ML

    Miriam Ladická, MD

    Department of Clinical Oncology 1, National Cancer Institute
    Bratislava, Slovakia

  • MG

    Michael Girschikofsky, MD

    1st Medical Department, Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz GmbH, Elisabethinen
    Linz, Oberosterreich, Austria

  • MH

    Mikuláš Hrubiško, MD

    Professor
    Clinic of Hematology and Transfusiology, Slovak Medical University, University Hospital Bratislava
    Bratislava, Slovakia

  • UJ

    Ulrich Jaeger, MD

    Professor of hematology
    Medical University of Vienna
    Vienna, Wien, Austria

  • CS

    Clemens A. Schmitt, MD

    Professor
    Department of Hematology and Internal Oncology, Kepler University Hospital, Johannes Kepler University
    Linz, Oberosterreich, Austria

  • MP

    Martin Pecherstorfer, MD

    Professor
    University Hospital Krems, Department of Internal Medicine 2, Karl Landsteiner Private University of Health Sciences
    Krems, Niederosterreich, Austria

  • EK

    Eva Králiková, MD

    Department of Hematology, FNsP F D Roosevelta
    Banská Bystrica, Slovakia

  • CB

    Cristina Burcoveanu, MD

    Clinic of Haematology, Regional Institute of Oncology Iasi
    Iasi, Romania

  • ES

    Emil Spassov, MD

    Clinic of Hematology, UMHAT St George and Medical University
    Plovdiv, Bulgaria

  • JJ

    Jana Jurkovikova, MD

    Louis Pasteur University Hospital Košice
    Košice, Slovakia

  • AP

    Andreas L. Petzer, MD

    Professor
    Internal Medicine I: Medical Oncology and Hematology, Ordensklinikum Linz GmbH, Barmherzige Schwestern
    Linz, Austria

  • GM

    Georgi G. Mihaylov, MD

    Professor
    Hematological Clinic NSHATHD
    Sofia, Bulgaria

  • JR

    Julian Raynov, MD

    Professor
    Clinic of Medical Hematology, Military Medical Academy
    Sofia, Bulgaria

  • HO

    Horst Oexle, MD

    Internal Medicine, Academic Teaching Hospital Hall in Triol, Hall in Tirol; present address: Reha Zentrum Münster
    Münster, Austria

  • AZ

    August F. Zabernigg, MD

    Department of Internal Medicine, County Hospital Kufstein
    Kufstein, Tirol, Austria

  • EF

    Emília Flochová, MD

    Department of Hematology and Transfusion, University Hospital Martin
    Martin, Slovakia

  • SP

    Stanislav Palášthy, MD

    Department of Clinical Hematology, FNsP, J A Reimana
    Prešov, Slovakia

  • TM

    Thomas Melchardt, MD

    Professor
    3rd Medical Dept. with Hematology, Medical Oncology, Rheumatology and Infectiology, Paracelsus Medical University
    Salzburg, Salzburg, Austria

  • JM

    Jiří Mayer, MD

    Professor
    27Department of Internal Medicine - Hematooncology, University Hospital Brno and Medical Faculty MU
    Brno, Czech Republic

  • RG

    Richard Greil, MD

    Professor
    Third Medical Department with Hematology, Medical Oncology, Rheumatology and Infectiology, Paracelsus Medical University, Salzburg, Austria; Salzburg Cancer Research Institute Center for Clinical Cancer and Immunology Trials, Salzburg, Austria; Cancer Cluster Salzburg, Salzburg, Austria
    Salzburg, Salzburg, Austria