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3225 Quality of Life in Newly Diagnosed Patients with Multiple Myeloma Randomized to Either Krd or Ktd Induction Therapy Followed By Carfilzomib Maintenance or Control (AGMT MM 02 trial)

Program: Oral and Poster Abstracts
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster III
Hematology Disease Topics & Pathways:
multiple myeloma, Diseases, Combinations, Therapies, Biological Processes, Plasma Cell Disorders, Lymphoid Malignancies, Clinically relevant
Monday, December 7, 2020, 7:00 AM-3:30 PM

Heinz Ludwig, MD1, Thomas Melchardt, MD, PhD2*, Johannes Andel, MD3*, Eberhard Gunsilius, MD4*, Siegfried Sormann, MD5*, Axel Hinke, PhD6*, Bernd L. Hartmann, MD7*, Klaus Podar, MD, PhD8, Wolfgang Willenbacher, MD, PhD4,9, Alexander Egle, MD2, Andreas Petzer, MD10, Niklas Zojer, MD11*, Ewald Wöll, MD12*, Reinhard Ruckser, MD13*, Boris Bozic, MD13*, Clemens A. Schmitt, MD14, Sigrid Machherndl-Spandl, MD15*, Maria-Theresa Krauth, MD16*, Martin Schreder, MD11*, Hermine Agis, MD16, Christoph Tinchon, MD17*, Michael Fillitz, MD18* and Richard Greil, MD2

1Wilhelminen Cancer Research Institute, c/o Department of Medicine I, Center for Oncology, Hematology, and Palliative Care, Clinic Ottakring, Vienna, Austria
2Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute-Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Paracelsus Medical University, Cancer Cluster Salzburg, Salzburg, Austria
3Department of Internal Medicine II, LKH Steyr, Steyr, Austria
4Department of Internal Medicine V, Hematology and Oncology, Medical University Innsbruck, Innsbruck, Austria
5Department of Internal Medicine, University Clinic Graz, Graz, Austria
6CCRC Cancer Clinical Research Consulting, Düsseldorf, Germany
7Department of Internal Medicine II, LKH Rankweil, Rankweil, Austria
8Department of Internal Medicine II, University Hospital Krems, Karl Landsteiner University of Health Sciences, Krems an der Donau, Lower Austria, Austria
9Oncotyrol, Center for personalized Cancer Medicine, Innsbruck, Austria
10Department of Internal Medicine I, Ordensklinikum Linz - BHS, Linz, Austria
11Department of Medicine I, Center for Oncology, Hematology, and Palliative Care, Clinic Ottakring, Vienna, Austria
12Department of Internal Medicine, KH Zams, Zams, Austria
13Department of Medicine II, Clinic Donaustadt, Vienna, Austria
14Clinic for Internal Medicine 3, Kepler University Clinic Linz, Linz, Austria
15Department of Internal Medicine I, Ordensklinikum Linz Elisabethinen, Linz, Austria
16Department of Internal Medicine I, Divison of Hematology and Hemostaseology, Medical University Vienna, Vienna, Austria
17Department of Internal Medicine, LKH Hochsteiermark, Leoben, Austria
18Third Department of Internal Medicine, Hanusch Hospital, Vienna, Austria

Introduction

Carfilzomib-based induction therapy is highly effective in newly diagnosed pts with multiple myeloma (NDMM), but information on quality of life (QoL) during first line and maintenance therapy is not available. Here, we analyze patient-reported QoL in transplant-non eligible (TNE) NDMM pts randomized to either KTd or KRd induction therapy followed by second randomization to carfilzomib maintenance, or control.

Patients and Methods

At time of analysis, 101 TNE pts with NDMM had been enrolled, but QoL data documented for ≥ 2 cycles were available in 78 pts so far (median age: 75 years, ISS stage I: 26.6%, II: 35.4%, III: 38.0%, ECOG status 0: 51.9%, 1: 48.1%). Patients were randomized to either 9 cycles KTd or KRd, and subsequently (46 pts with ≥PR) to either carfilzomib maintenance therapy (d1 and 15) or to control for 12 months. Carfilzomib was administered twice weekly (27mg/m2) during cycles 1 and 2, and thereafter weekly at a dose of 56mg/m2. Thalidomide was given daily at 100mg (50mg in pts ≥75 years), lenalidomide at 25mg, d1-21 per 4 week cycle, and dexamethasone at 40 mg (20mg in pts ³75 years) once weekly.

QoL was assessed by the QoL questionnaire EORTC QLQ-C30. Assessments were done at baseline, and monthly thereafter for 21 months. A two-sided t-test was used for comparison with the general population. Wilcoxon signed-rank tests were applied to evaluate differences in QoL dimensions within the treatment groups. A clinically meaningful improvement has been defined as a change of ≥10 score points.

Results

Comparison with the general population: Mean scores for health-related global QoL (54.1±22.6) and physical functioning (61.2±25.0) were significantly lower in pts compared to those reported for the general population of similar age (67.2±20.6, p<0.001, and 80.6±19.7, p<0.001, respectively) (Nolte S et al., Eur. J. Cancer 2019).

Induction therapy: Health-related global QoL showed a clinically relevant improvement during carfilzomib-based induction therapy in both treatment groups (KRd: 54.5±19.9 to 65.0±20.2, p=0.10, KTd 53.6±24.8 to 68.2 ± 19.4, p=0.04), but a statistically significant increase in score points was noted in the KTd arm only. For physical functioning, a clinically relevant improvement was noted solely in pts on KRd, but the increase was not statistically significant (59.2 ± 22 to 73.2 ± 23.8, p=0.15), while during KTd no relevant changes were noted. Further clinically relevant improvements during induction therapy were observed for role functioning (KTd: 45 ± 39.3 to 61.6 ± 33.5, p=0.08, KRD: 51.5 ± 34.9 to 66.7 ± 30.1, p=0.29), emotional functioning (KTd: 61.2 ± 27.4 to 73.2 ± 20.5, p=0.04, KRd: 58.3 ± 23.2 to 73 ± 26.7, p=0.10), and pain with a statistically significant decrease in respective scores in both arms (KTd: 47.7 ± 37.4, to 24.2 ± 26.1, p=0.01, KRd: 54.8 ± 33.2 to 20.8 ± 21.5, p<0.001)(Figure 1). Neuropathy, however, worsened clinically relevant and statistically significant in KTd treated pts (15.4 ± 24 to 27.8 ± 26.4, p=0.03), while during KRd treatment, no change was noted (22.2±30.8 to 22.2±28.0, p=0.66). Likewise, no changes were observed for nausea/vomiting, diarrhoea, constipation, fatigue, and cognitive function, while a clinically relevant improvement in social function was noted in pts during KRd induction (66.2±31.4 to 80.8±27.7, p=0.13).

Maintenance phase: Pts randomized to carfilzomib maintenance showed no clinically relevant change in health-related QoL score (70.3± 17 to 63.9±25.3), similar to the findings in the untreated controls, which showed a clinically not relevant improvement in scores (66.7.±21.0 to 75.9±18.8). The scores for physical functioning remained rather stable during the maintenance period and values at end of therapy or observation appeared similar between the carfilzomib (77.1±21.6) and the control group (83.7±25.4).

Conclusion

Health-related global QoL and physical functioning in our pts with TNE NDMM was significantly impaired at start of therapy compared to the general population. During carfilzomib-based induction TX, clinically meaningful improvements in health-related global QoL, physical (only in KTd), emotional, role, and social (only in KRd) functioning, and pain were achieved. Neuropathy worsened during KTd. Maintenance treatment with carfilzomib was well tolerated without a clinically relevant change during the treatment period or statistical significant difference to the untreated controls.

Disclosures: Ludwig: Seattle Genetics: Other: Advisory Boards; Sanofi: Other: Advisory Boards, Speakers Bureau; Bristol Myers: Other: Advisory Boards, Speakers Bureau; Janssen: Other: Advisory Boards, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Other: Advisory Boards, Research Funding, Speakers Bureau; Takeda: Research Funding. Podar: Amgen, BMS-Celgene, Janssen, Roche: Consultancy, Honoraria, Research Funding. Willenbacher: Amgen, Janssen, Takeda, BMS-Celgene: Consultancy, Honoraria, Research Funding. Petzer: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite-Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Schreder: BMS-Celgene, Amgen: Consultancy. Agis: Janssen: Honoraria, Research Funding; Amgen: Honoraria; BMS: Honoraria; Celgene: Honoraria; Takeda: Honoraria. Greil: Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; Daiichi Sankyo, Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; MSD Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; Astra zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; BMS/celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding; F. Hoffmann-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accomodations, expenses, Research Funding.

OffLabel Disclosure: Use of Carfilzomib in myeloma first-line treatment

*signifies non-member of ASH