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DARATUMUMAB (D) IN COMBINATION WITH VD OR D-RD IN RELAPSED OR REFRACTORY MULTIPLE MYELOMA: SUBGROUP ANALYSIS OF CASTOR AND POLLUX STUDIES IN PATIENTS WITH EARLY OR LATE RELAPSE AFTER INITIAL THERAPY
Author(s): ,
Andrew Spencer
Affiliations:
Malignant Haematology and Stem Cell Transplantation Service,Alfred Health-Monash University,Melbourne,Australie;Malignant Haematology and Stem Cell Transplantation Service,Alfred Health-Monash University,Melbourne,Australien;Malignant Haematology and Stem Cell Transplantation Service,Alfred Health-Monash University,Melbourne,Australia;Malignant Haematology and Stem Cell Transplantation Service,Alf
,
Philippe Moreau
Affiliations:
Hematology Department,University Hospital Hôtel-Dieu,Nantes,France;Hematology Department,University Hospital Hôtel-Dieu,Nantes,Frankreich;Hematology Department,University Hospital Hôtel-Dieu,Nantes,Francia;Hematology Department,University Hospital Hôtel-Dieu,Nantes,France;Hematology Department,University Hospital Hôtel-Dieu,Nantes,Francia;Hematology Department,University Hospital Hôtel-Dieu,Nantes
,
Maria-Victoria Mateos
Affiliations:
University Hospital of Salamanca/IBSAL/Cancer Research Center-IBMCC (USAL-CSIC),Salamanca,Espagne;University Hospital of Salamanca/IBSAL/Cancer Research Center-IBMCC (USAL-CSIC),Salamanca,Spanien;University Hospital of Salamanca/IBSAL/Cancer Research Center-IBMCC (USAL-CSIC),Salamanca,Spagna;University Hospital of Salamanca/IBSAL/Cancer Research Center-IBMCC (USAL-CSIC),Salamanca,Spain;University
,
Hartmut Goldschmidt
Affiliations:
University Hospital Heidelberg, Internal Medicine V and National Center for Tumor Diseases (NCT),Heidelberg,Allemagne;University Hospital Heidelberg, Internal Medicine V and National Center for Tumor Diseases (NCT),Heidelberg,Deutschland;University Hospital Heidelberg, Internal Medicine V and National Center for Tumor Diseases (NCT),Heidelberg,Germania;University Hospital Heidelberg, Internal Medi
,
Kenshi Suzuki
Affiliations:
Department of Hematology,Japanese Red Cross Medical Center,Tokyo,Japon;Department of Hematology,Japanese Red Cross Medical Center,Tokyo,Japan;Department of Hematology,Japanese Red Cross Medical Center,Tokyo,Giappone;Department of Hematology,Japanese Red Cross Medical Center,Tokyo,Japan;Department of Hematology,Japanese Red Cross Medical Center,Tokyo,Japón;Department of Hematology,Japanese Red Cros
,
Mark-David Levin
Affiliations:
Albert Schweitzer Hospital,Dordrecht,Pays-bas;Albert Schweitzer Hospital,Dordrecht,Niederlande;Albert Schweitzer Hospital,Dordrecht,Paesi Bassi;Albert Schweitzer Hospital,Dordrecht,Netherland;Albert Schweitzer Hospital,Dordrecht,Países Bajos;Albert Schweitzer Hospital,Dordrecht,Nederland;Albert Schweitzer Hospital,Dordrecht,Holanda;Albert Schweitzer Hospital,Dordrecht,Нидерланды;Albert Schweitzer
,
Pieter Sonneveld
Affiliations:
Erasmus MC Cancer Institute,Rotterdam,Pays-bas;Erasmus MC Cancer Institute,Rotterdam,Niederlande;Erasmus MC Cancer Institute,Rotterdam,Paesi Bassi;Erasmus MC Cancer Institute,Rotterdam,Netherland;Erasmus MC Cancer Institute,Rotterdam,Países Bajos;Erasmus MC Cancer Institute,Rotterdam,Nederland;Erasmus MC Cancer Institute,Rotterdam,Holanda;Erasmus MC Cancer Institute,Rotterdam,Нидерланды;Erasmus MC
,
Sung-Soo Yoon
Affiliations:
Department of Internal Medicine,Seoul National University College of Medicine,Seoul,Corée, République De;Department of Internal Medicine,Seoul National University College of Medicine,Seoul,Corea del Sud;Department of Internal Medicine,Seoul National University College of Medicine,Seoul,South Korea,Republic;Department of Internal Medicine,Seoul National University College of Medicine,Seoul,Zuid Kor
,
Saad Z. Usmani
Affiliations:
Memorial Sloan Kettering Cancer Center,New York, NY,États-unis;Memorial Sloan Kettering Cancer Center,New York, NY,Vereinigte Staaten;Memorial Sloan Kettering Cancer Center,New York, NY,Stati Uniti;Memorial Sloan Kettering Cancer Center,New York, NY,United States;Memorial Sloan Kettering Cancer Center,New York, NY,Estados Unidos;Memorial Sloan Kettering Cancer Center,New York, NY,Verenigde Staten;
,
Katja Weisel
Affiliations:
Department of Oncology,Hematology and Bone Marrow Transplantation With Section of Pneumology, University Medical Center Hamburg-Eppendorf,Hamburg,Allemagne;Department of Oncology,Hematology and Bone Marrow Transplantation With Section of Pneumology, University Medical Center Hamburg-Eppendorf,Hamburg,Deutschland;Department of Oncology,Hematology and Bone Marrow Transplantation With Section of Pneu
,
Donna Reece
Affiliations:
Department of Medical Oncology and Hematology,Princess Margaret Cancer Centre,Toronto,Canada;Department of Medical Oncology and Hematology,Princess Margaret Cancer Centre,Toronto,Kanada;Department of Medical Oncology and Hematology,Princess Margaret Cancer Centre,Toronto,Canada;Department of Medical Oncology and Hematology,Princess Margaret Cancer Centre,Toronto,Canada;Department of Medical Oncolo
,
Tahamtan Ahmadi
Affiliations:
Genmab US, Inc.,Plainsboro, NJ,États-unis;Genmab US, Inc.,Plainsboro, NJ,Vereinigte Staaten;Genmab US, Inc.,Plainsboro, NJ,Stati Uniti;Genmab US, Inc.,Plainsboro, NJ,United States;Genmab US, Inc.,Plainsboro, NJ,Estados Unidos;Genmab US, Inc.,Plainsboro, NJ,Verenigde Staten;Genmab US, Inc.,Plainsboro, NJ,Estados Unidos;Genmab US, Inc.,Plainsboro, NJ,United States;Genmab US, Inc.,Plainsboro, NJ,USA
,
Huiling Pei
Affiliations:
Janssen Research & Development, LLC,Titusville, NJ,États-unis;Janssen Research & Development, LLC,Titusville, NJ,Vereinigte Staaten;Janssen Research & Development, LLC,Titusville, NJ,Stati Uniti;Janssen Research & Development, LLC,Titusville, NJ,United States;Janssen Research & Development, LLC,Titusville, NJ,Estados Unidos;Janssen Research & Develop
,
Wendy Garvin Mayo
Affiliations:
Janssen Research & Development, LLC,Raritan, NJ,États-unis;Janssen Research & Development, LLC,Raritan, NJ,Vereinigte Staaten;Janssen Research & Development, LLC,Raritan, NJ,Stati Uniti;Janssen Research & Development, LLC,Raritan, NJ,United States;Janssen Research & Development, LLC,Raritan, NJ,Estados Unidos;Janssen Research & Development, LLC,Rarit
,
Xue Gai
Affiliations:
Janssen Research & Development, LLC,Beijing,Chine;Janssen Research & Development, LLC,Beijing,China;Janssen Research & Development, LLC,Beijing,Cina;Janssen Research & Development, LLC,Beijing,China;Janssen Research & Development, LLC,Beijing,China;Janssen Research & Development, LLC,Beijing,China;Janssen Research & Development, LLC,Beijing,C
,
Jodi Carey
Affiliations:
Janssen Research & Development, LLC,Spring House, PA,États-unis;Janssen Research & Development, LLC,Spring House, PA,Vereinigte Staaten;Janssen Research & Development, LLC,Spring House, PA,Stati Uniti;Janssen Research & Development, LLC,Spring House, PA,United States;Janssen Research & Development, LLC,Spring House, PA,Estados Unidos;Janssen Research &am
,
Robin Carson
Affiliations:
Janssen Research & Development, LLC,Spring House, PA,États-unis;Janssen Research & Development, LLC,Spring House, PA,Vereinigte Staaten;Janssen Research & Development, LLC,Spring House, PA,Stati Uniti;Janssen Research & Development, LLC,Spring House, PA,United States;Janssen Research & Development, LLC,Spring House, PA,Estados Unidos;Janssen Research &am
Meletios A. Dimopoulos
Affiliations:
National and Kapodistrian University of Athens,Athens,Grèce;National and Kapodistrian University of Athens,Athens,Griechenland;National and Kapodistrian University of Athens,Athens,Grecia;National and Kapodistrian University of Athens,Athens,Greece;National and Kapodistrian University of Athens,Athens,Grecia;National and Kapodistrian University of Athens,Athens,Griekenland;National and Kapodistria
(Abstract release date: 05/26/22) EHA Library. Spencer A. 06/10/22; 357793; P933
Andrew Spencer
Andrew Spencer
Contributions
Abstract
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P933

Type: Poster presentation

Session title: Myeloma and other monoclonal gammopathies - Clinical

Background
High-risk multiple myeloma (MM) is often defined based on cytogenetic abnormalities (ie, t[4;14], t[14;16], and/or del17p); however, patients who relapse early (12-18 months) after initial therapy are considered a functional high-risk group that is also associated with poor prognosis. Daratumumab (DARA), a human IgGk monoclonal antibody targeting CD38, is approved in combination with standard-of-care regimens for MM. In the phase 3 CASTOR and POLLUX studies, DARA in combination with bortezomib plus dexamethasone (D-Vd) and lenalidomide plus dexamethasone (D-Rd) significantly improved progression-free survival (PFS), regardless of cytogenetic risk, and achieved higher rates of complete response or better (CR) and minimal residual disease (MRD)–negativity vs Vd or Rd alone in patients with RRMM.

Aims
In this post-hoc analyses of CASTOR and POLLUX we evaluated D-Vd vs Vd and D-Rd vs Rd in patient subgroups with 1 prior line of therapy based on timing of relapse (early or late) after initiation of the first line of therapy.

Methods
In CASTOR and POLLUX, patients with RRMM and 1 prior line of therapy were randomized to D-Vd/Vd or D-Rd/Rd, respectively. The primary endpoint was PFS. In this analysis, the early relapse subgroup included patients with 1 prior line of therapy who relapsed <18 months after initiating their first line of therapy; patients with 1 prior line of therapy who relapsed 18 months after initiating their first line of therapy were included in the late relapse subgroup.

Results
49 and 186 patients from CASTOR and 99 and 196 patients from POLLUX were included in the early relapse and late relapse subgroups, respectively. Median follow-up was 72.6 months (CASTOR) and 79.7 months (POLLUX). PFS consistently favored the DARA-containing regimens across subgroups (Table). In CASTOR, CR rates were higher with D-Vd vs Vd in the early relapse (21% vs 17%; P = 0.7360) and late relapse (51% vs 14%; P <0.0001) subgroups. In POLLUX, CR rates were higher with D-Rd vs Rd in the early relapse (53% vs 12%; P <0.0001) and late relapse (62% vs 38%; P = 0.0012) subgroups. MRD-negativity rates (10–5) were higher with D-Vd/D-Rd vs Vd/Rd regardless of relapse timing (CASTOR: early, 13% vs 0%; P = 0.1476; late, 23% vs 3%; P <0.0001; POLLUX: early, 30% vs 4%; P = 0.0006; late, 34% vs 14%; P = 0.0009).

Conclusion
These post hoc analyses of CASTOR and POLLUX showed PFS and depth of response benefits of DARA-containing regimens in patients with 1 prior line of therapy, regardless of relapse timing (early or late). Our results support the use of D-Vd and D-Rd in RRMM, including in patients who are considered functional high risk.

Keyword(s): CD38, Immune therapy, Multiple myeloma



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P933

Type: Poster presentation

Session title: Myeloma and other monoclonal gammopathies - Clinical

Background
High-risk multiple myeloma (MM) is often defined based on cytogenetic abnormalities (ie, t[4;14], t[14;16], and/or del17p); however, patients who relapse early (12-18 months) after initial therapy are considered a functional high-risk group that is also associated with poor prognosis. Daratumumab (DARA), a human IgGk monoclonal antibody targeting CD38, is approved in combination with standard-of-care regimens for MM. In the phase 3 CASTOR and POLLUX studies, DARA in combination with bortezomib plus dexamethasone (D-Vd) and lenalidomide plus dexamethasone (D-Rd) significantly improved progression-free survival (PFS), regardless of cytogenetic risk, and achieved higher rates of complete response or better (CR) and minimal residual disease (MRD)–negativity vs Vd or Rd alone in patients with RRMM.

Aims
In this post-hoc analyses of CASTOR and POLLUX we evaluated D-Vd vs Vd and D-Rd vs Rd in patient subgroups with 1 prior line of therapy based on timing of relapse (early or late) after initiation of the first line of therapy.

Methods
In CASTOR and POLLUX, patients with RRMM and 1 prior line of therapy were randomized to D-Vd/Vd or D-Rd/Rd, respectively. The primary endpoint was PFS. In this analysis, the early relapse subgroup included patients with 1 prior line of therapy who relapsed <18 months after initiating their first line of therapy; patients with 1 prior line of therapy who relapsed 18 months after initiating their first line of therapy were included in the late relapse subgroup.

Results
49 and 186 patients from CASTOR and 99 and 196 patients from POLLUX were included in the early relapse and late relapse subgroups, respectively. Median follow-up was 72.6 months (CASTOR) and 79.7 months (POLLUX). PFS consistently favored the DARA-containing regimens across subgroups (Table). In CASTOR, CR rates were higher with D-Vd vs Vd in the early relapse (21% vs 17%; P = 0.7360) and late relapse (51% vs 14%; P <0.0001) subgroups. In POLLUX, CR rates were higher with D-Rd vs Rd in the early relapse (53% vs 12%; P <0.0001) and late relapse (62% vs 38%; P = 0.0012) subgroups. MRD-negativity rates (10–5) were higher with D-Vd/D-Rd vs Vd/Rd regardless of relapse timing (CASTOR: early, 13% vs 0%; P = 0.1476; late, 23% vs 3%; P <0.0001; POLLUX: early, 30% vs 4%; P = 0.0006; late, 34% vs 14%; P = 0.0009).

Conclusion
These post hoc analyses of CASTOR and POLLUX showed PFS and depth of response benefits of DARA-containing regimens in patients with 1 prior line of therapy, regardless of relapse timing (early or late). Our results support the use of D-Vd and D-Rd in RRMM, including in patients who are considered functional high risk.

Keyword(s): CD38, Immune therapy, Multiple myeloma



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.

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