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RANDOMIZED COMPARISON BETWEEN KRD AND KTD INDUCTION, FOLLOWED BY K MAINTENANCE OR OBSERVATION IN TRANSPLANT NON-ELIGIBLE PATIENTS WITH NDMM (AGMT-MM02 TRIAL)
Author(s): ,
Heinz Ludwig
Affiliations:
Wilhelminen Cancer Research Institute,Vienna,Autriche;Wilhelminen Cancer Research Institute,Vienna,Österreich;Wilhelminen Cancer Research Institute,Vienna,Austria;Wilhelminen Cancer Research Institute,Vienna,Austria;Wilhelminen Cancer Research Institute,Vienna,Austria;Wilhelminen Cancer Research Institute,Vienna,Oostenrijk;Wilhelminen Cancer Research Institute,Vienna,Áustria;Wilhelminen Cancer Res
,
Thomas Melchardt
Affiliations:
Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute – Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR),Paracelsius Medical University, Cancer Cluster Salzburg,Salzburg,Autriche;Department of Internal Medicine III with Haematology, Medical Oncology, Haemost
,
Siegfried Sormann
Affiliations:
Department of Internal Medicine,University Clinic Graz,Graz,Autriche;Department of Internal Medicine,University Clinic Graz,Graz,Österreich;Department of Internal Medicine,University Clinic Graz,Graz,Austria;Department of Internal Medicine,University Clinic Graz,Graz,Austria;Department of Internal Medicine,University Clinic Graz,Graz,Austria;Department of Internal Medicine,University Clinic Graz,G
,
Niklas Zojer
Affiliations:
Department of Medicine I,Clinic Ottakring,Vienna,Autriche;Department of Medicine I,Clinic Ottakring,Vienna,Österreich;Department of Medicine I,Clinic Ottakring,Vienna,Austria;Department of Medicine I,Clinic Ottakring,Vienna,Austria;Department of Medicine I,Clinic Ottakring,Vienna,Austria;Department of Medicine I,Clinic Ottakring,Vienna,Oostenrijk;Department of Medicine I,Clinic Ottakring,Vienna,Áu
,
Johannes Andel
Affiliations:
Department of Internal Medicine IIr,Pyhrn-Eisenwurzen Klinikum Steyr,Steyr,Autriche;Department of Internal Medicine IIr,Pyhrn-Eisenwurzen Klinikum Steyr,Steyr,Österreich;Department of Internal Medicine IIr,Pyhrn-Eisenwurzen Klinikum Steyr,Steyr,Austria;Department of Internal Medicine IIr,Pyhrn-Eisenwurzen Klinikum Steyr,Steyr,Austria;Department of Internal Medicine IIr,Pyhrn-Eisenwurzen Klinikum S
,
Bernd Hartmann
Affiliations:
Department of Internal Medicine II,LKH Rankweil,Rankweil,Autriche;Department of Internal Medicine II,LKH Rankweil,Rankweil,Österreich;Department of Internal Medicine II,LKH Rankweil,Rankweil,Austria;Department of Internal Medicine II,LKH Rankweil,Rankweil,Austria;Department of Internal Medicine II,LKH Rankweil,Rankweil,Austria;Department of Internal Medicine II,LKH Rankweil,Rankweil,Oostenrijk;Dep
,
Christoph Tinchon
Affiliations:
Department of Internal Medicine,LKH Hochsteiermark,Leoben,Autriche;Department of Internal Medicine,LKH Hochsteiermark,Leoben,Österreich;Department of Internal Medicine,LKH Hochsteiermark,Leoben,Austria;Department of Internal Medicine,LKH Hochsteiermark,Leoben,Austria;Department of Internal Medicine,LKH Hochsteiermark,Leoben,Austria;Department of Internal Medicine,LKH Hochsteiermark,Leoben,Oostenri
,
Eberhard Gunsilius
Affiliations:
Department of Internal Medicine V,Medical University Innsbruck,Innsbruck,Autriche;Department of Internal Medicine V,Medical University Innsbruck,Innsbruck,Österreich;Department of Internal Medicine V,Medical University Innsbruck,Innsbruck,Austria;Department of Internal Medicine V,Medical University Innsbruck,Innsbruck,Austria;Department of Internal Medicine V,Medical University Innsbruck,Innsbruck
,
Klaus Podar
Affiliations:
Department of Internal Medicine II,University Hospital Krems, Karl Landsteiner University of Health Sciences,Krems,Autriche;Department of Internal Medicine II,University Hospital Krems, Karl Landsteiner University of Health Sciences,Krems,Österreich;Department of Internal Medicine II,University Hospital Krems, Karl Landsteiner University of Health Sciences,Krems,Austria;Department of Internal Medi
,
Alexander Egle
Affiliations:
Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute – Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR),Paracelsius Medical University, Cancer Cluster Salzburg,Salzburg,Autriche;Department of Internal Medicine III with Haematology, Medical Oncology, Haemost
,
Wolfgang Willenbacher
Affiliations:
Department of Internal Medicine V,Medical University Innsbruck,Innsbruck,Autriche;Department of Internal Medicine V,Medical University Innsbruck,Innsbruck,Österreich;Department of Internal Medicine V,Medical University Innsbruck,Innsbruck,Austria;Department of Internal Medicine V,Medical University Innsbruck,Innsbruck,Austria;Department of Internal Medicine V,Medical University Innsbruck,Innsbruck
,
Ewald Wöll
Affiliations:
Department of Internal Medicine,KH Zams,Zams,Autriche;Department of Internal Medicine,KH Zams,Zams,Österreich;Department of Internal Medicine,KH Zams,Zams,Austria;Department of Internal Medicine,KH Zams,Zams,Austria;Department of Internal Medicine,KH Zams,Zams,Austria;Department of Internal Medicine,KH Zams,Zams,Oostenrijk;Department of Internal Medicine,KH Zams,Zams,Áustria;Department of Internal
,
Martin Schreder
Affiliations:
Department of Medicine I,Clinic Ottakring,Vienna,Autriche;Department of Medicine I,Clinic Ottakring,Vienna,Österreich;Department of Medicine I,Clinic Ottakring,Vienna,Austria;Department of Medicine I,Clinic Ottakring,Vienna,Austria;Department of Medicine I,Clinic Ottakring,Vienna,Austria;Department of Medicine I,Clinic Ottakring,Vienna,Oostenrijk;Department of Medicine I,Clinic Ottakring,Vienna,Áu
,
Reinhard Ruckser
Affiliations:
Department of Medicine II,Clinic Donaustadt,Vienna,Autriche;Department of Medicine II,Clinic Donaustadt,Vienna,Österreich;Department of Medicine II,Clinic Donaustadt,Vienna,Austria;Department of Medicine II,Clinic Donaustadt,Vienna,Austria;Department of Medicine II,Clinic Donaustadt,Vienna,Austria;Department of Medicine II,Clinic Donaustadt,Vienna,Oostenrijk;Department of Medicine II,Clinic Donaus
,
Boris Bozic
Affiliations:
Department of Medicine II,Clinic Donaustadt,Vienna,Autriche;Department of Medicine II,Clinic Donaustadt,Vienna,Österreich;Department of Medicine II,Clinic Donaustadt,Vienna,Austria;Department of Medicine II,Clinic Donaustadt,Vienna,Austria;Department of Medicine II,Clinic Donaustadt,Vienna,Austria;Department of Medicine II,Clinic Donaustadt,Vienna,Oostenrijk;Department of Medicine II,Clinic Donaus
,
Maria-Theresa Krauth
Affiliations:
Department of Internal Medicine I, Division Hematology & Hemostaseology,Medical University Vienna,Vienna,Autriche;Department of Internal Medicine I, Division Hematology & Hemostaseology,Medical University Vienna,Vienna,Österreich;Department of Internal Medicine I, Division Hematology & Hemostaseology,Medical University Vienna,Vienna,Austria;Department of Internal Medicine I
,
Andreas Petzer
Affiliations:
Department of Internal Medicine I,Ordensklinikum Linz Barmherzige Schwestern,Linz,Autriche;Department of Internal Medicine I,Ordensklinikum Linz Barmherzige Schwestern,Linz,Österreich;Department of Internal Medicine I,Ordensklinikum Linz Barmherzige Schwestern,Linz,Austria;Department of Internal Medicine I,Ordensklinikum Linz Barmherzige Schwestern,Linz,Austria;Department of Internal Medicine I,Or
,
Clemens Schmitt
Affiliations:
Clinic for Internal Medicine 3,Kepler University Clinic Linz,Linz,Autriche;Clinic for Internal Medicine 3,Kepler University Clinic Linz,Linz,Österreich;Clinic for Internal Medicine 3,Kepler University Clinic Linz,Linz,Austria;Clinic for Internal Medicine 3,Kepler University Clinic Linz,Linz,Austria;Clinic for Internal Medicine 3,Kepler University Clinic Linz,Linz,Austria;Clinic for Internal Medici
,
Sigrid Machherndl-Spandl
Affiliations:
Ordensklinikum Linz Elisabethinen,Linz,Autriche;Ordensklinikum Linz Elisabethinen,Linz,Österreich;Ordensklinikum Linz Elisabethinen,Linz,Austria;Ordensklinikum Linz Elisabethinen,Linz,Austria;Ordensklinikum Linz Elisabethinen,Linz,Austria;Ordensklinikum Linz Elisabethinen,Linz,Oostenrijk;Ordensklinikum Linz Elisabethinen,Linz,Áustria;Ordensklinikum Linz Elisabethinen,Linz,Австрия;Ordensklinikum Li
,
Hermine Agis
Affiliations:
Department of Internal Medicine I, Division of Oncology,Medical University Vienna,Vienna,Autriche;Department of Internal Medicine I, Division of Oncology,Medical University Vienna,Vienna,Österreich;Department of Internal Medicine I, Division of Oncology,Medical University Vienna,Vienna,Austria;Department of Internal Medicine I, Division of Oncology,Medical University Vienna,Vienna,Austria;Departme
,
Michael Fillitz
Affiliations:
Department of Internal Medicine,Hanusch Krankenhaus,Vienna,Autriche;Department of Internal Medicine,Hanusch Krankenhaus,Vienna,Österreich;Department of Internal Medicine,Hanusch Krankenhaus,Vienna,Austria;Department of Internal Medicine,Hanusch Krankenhaus,Vienna,Austria;Department of Internal Medicine,Hanusch Krankenhaus,Vienna,Austria;Department of Internal Medicine,Hanusch Krankenhaus,Vienna,Oo
,
Wolfram Pönisch
Affiliations:
Medical Clinic and Policlinic I,University Clinic Leipzig,Leipzig,Allemagne;Medical Clinic and Policlinic I,University Clinic Leipzig,Leipzig,Deutschland;Medical Clinic and Policlinic I,University Clinic Leipzig,Leipzig,Germania;Medical Clinic and Policlinic I,University Clinic Leipzig,Leipzig,Germany;Medical Clinic and Policlinic I,University Clinic Leipzig,Leipzig,Alemania;Medical Clinic and Pol
,
Stefan Knop
Affiliations:
Medical Clinic and Policlinic II,University Clinic Würzburg, Würzburg,Allemagne;Medical Clinic and Policlinic II,University Clinic Würzburg, Würzburg,Deutschland;Medical Clinic and Policlinic II,University Clinic Würzburg, Würzburg,Germania;Medical Clinic and Policlinic II,University Clinic Würzburg, Würzburg,Germany;Medical Clinic and Policlinic II,University Clinic Würzburg, Würzburg,Alemania;Me
,
Bruno Paiva
Affiliations:
Clinica Universidad de Navarra,Pamplona,Espagne;Clinica Universidad de Navarra,Pamplona,Spanien;Clinica Universidad de Navarra,Pamplona,Spagna;Clinica Universidad de Navarra,Pamplona,Spain;Clinica Universidad de Navarra,Pamplona,España;Clinica Universidad de Navarra,Pamplona,Spanje;Clinica Universidad de Navarra,Pamplona,Espanha;Clinica Universidad de Navarra,Pamplona,Испания;Clinica Universidad d
Richard Greil
Affiliations:
Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute – Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR),Paracelsius Medical University, Cancer Cluster Salzburg,Salzburg,Autriche;Department of Internal Medicine III with Haematology, Medical Oncology, Haemost
(Abstract release date: 05/12/22) EHA Library. Ludwig H. 06/10/22; 357043; S179
Heinz Ludwig
Heinz Ludwig
Contributions
Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S179

Type: Oral Presentation

Session title: Newly diagnosed multiple myeloma

Background

Carfilzomib (K)-based combinations have been established as effective frontline and relapse regimens in pts with multiple myeloma (MM).

Aims

In this randomized phase II trial we evaluated the impact of either Revlimid (R) or Thalidomide (T) as combination partner for K and dexamethasone (KRd or KTd) on outcome in pts with newly diagnosed MM (NDMM) not eligible for autologous transplantation (TNE). Further, we evaluated the role of one year K maintenance therapy compared to observation.

Methods

One hundred twenty two pts have been enrolled (ITT population). Median age was 75 yrs, ISS stage I/II/III: 29 (23.8%)/48 (39.3%)/45 (36.9%), ECOG stage 0/1: 64 (52.5%) / 58 (47.5%). t(4;14) ± del17p was noted in 15 (16.3%) of 92 pts with results available. Pts were randomized to 9 cycles of KRd or KTd, and 107 pts received at least one full cycle. Carfilzomib (K) was started with 20mg/m2 at d 1 of cycle 1, and was continued with 27mg/m2 for the first 2 cycles (d 1+2, 8+9, 15+16 schedule); followed by K administration at 57mg/m2 once weekly for a 28 d cycle. Thalidomide 100mg/d (50mg in pts >75 yrs of age), d 1-28, or Revlimid 25mg/d (15mg in pts ³75 yrs of age) d 1-21. Dexamethasone 40mg (20mg in pts ³75 yrs of age) once/week. After induction, pts with ³SD were randomized to K maintenance (d 1 and 15) for 12 cycles or observation. MRD was assessed by NGF with a sensitivity of 10-6 in pts with ≥VGPR. Survival estimates were calculated according to Kaplan-Meier and survival curves were compared with the log-rank test. PFS and OS results presented are given for the ITT population. This trial is registered on clinicaltrials.gov (NCT02891811).

Results

Median follow-up was 25.3 mos, 15 pts discontinued therapy within the first cycle due to patient (3) or investigator (1) decision, AE/toxicity (8), death or progressive disease (2) or other reason (1). Overall response rate was 91.3% in the entire group with available data (n=115). Results for sCR, CR, VGPR, PR, and ORR for KRd and KTd were similar between both groups (7.3%/10.0%, 27.3%/33.3%, 38.2%/35.0%, 14.5/16.7%, 87.3%/95.0%, respectively). Minor response was noted in 4 (3.5%), stable disease in 5 (4.3%) and progressive disease in 1 (0.8%) pts.

PFS (median 26.9 and 23.5 mos, p=0.832) and OS (not reached vs 52.2 mos, p=0.398) were similar between the KRd and KTd group, respectively. The OS rate at 36 mos was 82% in both groups. MRD testing was performed in 57 pts at time of CR/VGPR. Of those, 43.9%, (20.5% of the ITT group) pts were found to be MRDneg. PFS was significantly longer in MRDneg vs. MRDpos pts (p=0.003).  Seventy six pts were randomized to K maintenance therapy or observation. Median PFS was numerically higher in the pts with K maintenance treatment (median 33.0 vs 24.0, p=0.714), but the difference was not statistically significant. Data on OS are not mature yet (only 9 events).

Grade 3/4 hematologic AEs were anemia (4.1%), leukopenia (0.8%), thrombocytopenia (7.4%), while non-hematologic grade 3/4 AEs were infection (20.5%), GI-disorders (7.4%), hypertension (7.4%), renal and cardiac impairment/failure (6.6% and 8.2% respectively).

Conclusion

Our data show similar high efficacy of KRd and KTd in elderly NTE NDMM pts, including no difference in ORR (KRd and KTd, 87.3% and 95%, respectively), PFS and OS. Overall survival rate at 3 yrs was 82%. Median PFS was significantly longer in MRDneg pts. PFS was numerically, but not statistically longer in pts on K maintenance vs observation. Treatment was associated with an acceptable tolerance profile.

Keyword(s): Clinical outcome, Clinical trial, Multiple myeloma, Randomized

Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S179

Type: Oral Presentation

Session title: Newly diagnosed multiple myeloma

Background

Carfilzomib (K)-based combinations have been established as effective frontline and relapse regimens in pts with multiple myeloma (MM).

Aims

In this randomized phase II trial we evaluated the impact of either Revlimid (R) or Thalidomide (T) as combination partner for K and dexamethasone (KRd or KTd) on outcome in pts with newly diagnosed MM (NDMM) not eligible for autologous transplantation (TNE). Further, we evaluated the role of one year K maintenance therapy compared to observation.

Methods

One hundred twenty two pts have been enrolled (ITT population). Median age was 75 yrs, ISS stage I/II/III: 29 (23.8%)/48 (39.3%)/45 (36.9%), ECOG stage 0/1: 64 (52.5%) / 58 (47.5%). t(4;14) ± del17p was noted in 15 (16.3%) of 92 pts with results available. Pts were randomized to 9 cycles of KRd or KTd, and 107 pts received at least one full cycle. Carfilzomib (K) was started with 20mg/m2 at d 1 of cycle 1, and was continued with 27mg/m2 for the first 2 cycles (d 1+2, 8+9, 15+16 schedule); followed by K administration at 57mg/m2 once weekly for a 28 d cycle. Thalidomide 100mg/d (50mg in pts >75 yrs of age), d 1-28, or Revlimid 25mg/d (15mg in pts ³75 yrs of age) d 1-21. Dexamethasone 40mg (20mg in pts ³75 yrs of age) once/week. After induction, pts with ³SD were randomized to K maintenance (d 1 and 15) for 12 cycles or observation. MRD was assessed by NGF with a sensitivity of 10-6 in pts with ≥VGPR. Survival estimates were calculated according to Kaplan-Meier and survival curves were compared with the log-rank test. PFS and OS results presented are given for the ITT population. This trial is registered on clinicaltrials.gov (NCT02891811).

Results

Median follow-up was 25.3 mos, 15 pts discontinued therapy within the first cycle due to patient (3) or investigator (1) decision, AE/toxicity (8), death or progressive disease (2) or other reason (1). Overall response rate was 91.3% in the entire group with available data (n=115). Results for sCR, CR, VGPR, PR, and ORR for KRd and KTd were similar between both groups (7.3%/10.0%, 27.3%/33.3%, 38.2%/35.0%, 14.5/16.7%, 87.3%/95.0%, respectively). Minor response was noted in 4 (3.5%), stable disease in 5 (4.3%) and progressive disease in 1 (0.8%) pts.

PFS (median 26.9 and 23.5 mos, p=0.832) and OS (not reached vs 52.2 mos, p=0.398) were similar between the KRd and KTd group, respectively. The OS rate at 36 mos was 82% in both groups. MRD testing was performed in 57 pts at time of CR/VGPR. Of those, 43.9%, (20.5% of the ITT group) pts were found to be MRDneg. PFS was significantly longer in MRDneg vs. MRDpos pts (p=0.003).  Seventy six pts were randomized to K maintenance therapy or observation. Median PFS was numerically higher in the pts with K maintenance treatment (median 33.0 vs 24.0, p=0.714), but the difference was not statistically significant. Data on OS are not mature yet (only 9 events).

Grade 3/4 hematologic AEs were anemia (4.1%), leukopenia (0.8%), thrombocytopenia (7.4%), while non-hematologic grade 3/4 AEs were infection (20.5%), GI-disorders (7.4%), hypertension (7.4%), renal and cardiac impairment/failure (6.6% and 8.2% respectively).

Conclusion

Our data show similar high efficacy of KRd and KTd in elderly NTE NDMM pts, including no difference in ORR (KRd and KTd, 87.3% and 95%, respectively), PFS and OS. Overall survival rate at 3 yrs was 82%. Median PFS was significantly longer in MRDneg pts. PFS was numerically, but not statistically longer in pts on K maintenance vs observation. Treatment was associated with an acceptable tolerance profile.

Keyword(s): Clinical outcome, Clinical trial, Multiple myeloma, Randomized

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