WAIT FOR SUGGESTIONS BY CATEGORY OR CONTINUE TYPING IN YOUR KEYWORDS
ENTER ONE OR MULTIPLE KEYWORDS & PRESS THE SEARCH BUTTON
Search
Favorites
Favorites
AdvancedMinimize
More ▾Less ▸
Clear
IMPROVED EFFICACY AFTER INCORPORATING AUTOLOGOUS STEM CELL TRANSPLANT (ASCT) INTO KRD TREATMENT WITH CARFILZOMIB (CFZ), LENALIDOMIDE (LEN), AND DEXAMETHASONE (DEX) IN NEWLY DIAGNOSED MULTIPLE MYELOMA
Author(s):
Andrzej Jakubowiak
,
Andrzej Jakubowiak
Affiliations: University of Chicago,Chicago, IL,United States
Noopur Raje
,
Noopur Raje
Affiliations: Massachussetts General Hospital,Boston, MA,United States
Ravi Vij
,
Ravi Vij
Affiliations: Washington University,Saint Louis, MO,United States
Donna Reece
,
Donna Reece
Affiliations: Princess Margaret Cancer Centre,Toronto,Canada
Jesus Berdeja
,
Jesus Berdeja
Affiliations: Sarah Cannon Research Institute,Nashville, TN,United States
David Vesole
,
David Vesole
Affiliations: John Theurer Cancer Center,Hackensack, NJ,United States
Sundar Jagannath
,
Sundar Jagannath
Affiliations: Mount Sinai Medical Center,New York, NY,United States
Craig Cole
,
Craig Cole
Affiliations: University of Michigan,Ann Arbor, MI,United States
Malek Faham
,
Malek Faham
Affiliations: Adaptive Biotechnologies,Seattle, WA,United States
Jennifer Nam
,
Jennifer Nam
Affiliations: University of Chicago,Chicago, IL,United States
Leonor Stephens
,
Leonor Stephens
Affiliations: University of Chicago,Chicago, IL,United States
Erica Severson
,
Erica Severson
Affiliations: University of Chicago,Chicago, IL,United States
Andrea Revethis
,
Andrea Revethis
Affiliations: University of Chicago,Chicago, IL,United States
Brittany Wolfe
,
Brittany Wolfe
Affiliations: University of Chicago,Chicago, IL,United States
Shaun Rosebeck
,
Shaun Rosebeck
Affiliations: University of Chicago,Chicago, IL,United States
Sandeep Gurbuxani
,
Sandeep Gurbuxani
Affiliations: University of Chicago,Chicago, IL,United States
Cara Rosenbaum
,
Cara Rosenbaum
Affiliations: University of Chicago,Chicago, IL,United States
Jagoda Jasielec
,
Jagoda Jasielec
Affiliations: Northshore University Health System,Evanston, IL,United States
Dominik Dytfeld
,
Dominik Dytfeld
Affiliations: NJ University of Medical Sciences,Poznan,Poland
Kent Griffith
,
Kent Griffith
Affiliations: University of Michigan,Ann Arbor, MI,United States
Todd Zimmerman
Todd Zimmerman
Affiliations: University of Chicago,Chicago, IL,United States
(Abstract release date: 05/19/16)
EHA Library. J. Jakubowiak A. 06/10/16; 135134; S101
Presentation during EHA21: On Friday, June 10, 2016 from 11:45 - 12:00
Location: Hall A1
Background In a phase 1/2 trial (N=53), extended treatment with KRd without (w/o) ASCT was highly active in newly diagnosed myeloma (NDMM) with stringent complete response (sCR) 55% and 3-year progression-free survival (PFS) 79%.
Aims In a subsequent phase 2 trial, we are evaluating whether extended KRd can be further improved by incorporating ASCT (KRd+ASCT). We report results from both trials after completion of enrollment into KRd+ASCT and after completion of KRd w/o ASCT (median follow-up [f/u] 4 years) as a historical control.
Methods Both studies enrolled patients (pts) with NDMM based on similar eligibility criteria except KRd+ASCT excluded transplant ineligible pts. The treatment schemas were generally similar between studies. In KRd+ASCT, pts received: four 28-day cycles of induction with CFZ IV 36 mg/m2 on Days (D) 1-2, 8-9, 15-16 (CFZ 20 mg/m2 for D1-2, C1 only), LEN PO D121 at 25 mg, DEX PO 40 mg/wk; followed by stem cell collection (SCC), melphalan 200 mg/m2 and ASCT; then KRd consolidation (C5-8) using the same doses and schedule except LEN 15 mg in C5 with the option to escalate to prior dose, and DEX reduced to 20 mg/wk; then KRd maintenance (C9-18) using the same doses as in C8 except CFZ on Days 1-2, 15-16 only. In KRd w/o ASCT, transplant-eligible pts underwent SCC after C4 then resumed KRd, and KRd maintenance was longer (C9-24). Both studies recommended single-agent LEN off study. The primary endpoint in KRd+ASCT is sCR at the end of C8. We hypothesized that an improvement of sCR from 30% at the end of C8 (historical KRd w/o ASCT) to >50% (KRd+ASCT) represents added benefit of ASCT with 5% type I error (2 sided) and supports further evaluation. Minimal residual disease (MRD) is evaluated by 10-color multiparameter flow cytometry (MFC, threshold 10-4-10‑5) and by next-generation sequencing (NGS, LymphoSIGHTTM, threshold at 10-6 for MRD negativity).
Results The current KRd+ASCT study enrolled 76 pts with 72 evaluable. Baseline characteristics were comparable between the KRd+ASCT and KRd w/o ASCT study populations, including median age (59 and 59y) and high-risk IMWG cytogenetics (36% and 33%). In the ongoing KRd+ASCT, 69 pts proceeded to ASCT at data cut-off (Jan 1, 2016), 50 completed KRd consolidation, and 26 KRd maintenance, with remaining pts on treatment, except 1 patient who progressed prior to transplant. At the end of C8, sCR was 72% for KRd+ASCT (n=50) vs 30% for KRd w/o ASCT (n=44) and 88% (n=26) vs 51% (n=41) at the end of C18. At median f/u of 17.8 months, 2-year PFS was 99% for KRd+ASCT vs 92% for KRd w/o ASCT at median f/u of 47.5 months. In KRd+ASCT, MRD by MFC was negative in 94% of pts tested (n=31) at the end of C8 and 95% of pts tested (n=19) at the end of C18. In KRd w/o ASCT, 4-year PFS was 69% overall, 78% in MRD-negative pts vs 60% in positive/unknown pts by MFC, and 100% in pts with MRD negative status by NGS. Updated MRD analyses and outcomes based on MRD status by both MFC and NGS will be presented at the meeting. The types and rates of adverse events (AEs) pre- and post-ASCT were comparable to AEs in KRd w/o ASCT.
Conclusion Recognizing limitations of cross-study comparisons, KRd+ASCT shows superior outcomes vs historical KRd w/o ASCT, supporting further evaluation in the randomized setting. Both KRd studies compare favorably to other NDMM studies.
Presentation during EHA21: On Friday, June 10, 2016 from 11:45 - 12:00
Location: Hall A1
Background In a phase 1/2 trial (N=53), extended treatment with KRd without (w/o) ASCT was highly active in newly diagnosed myeloma (NDMM) with stringent complete response (sCR) 55% and 3-year progression-free survival (PFS) 79%.
Aims In a subsequent phase 2 trial, we are evaluating whether extended KRd can be further improved by incorporating ASCT (KRd+ASCT). We report results from both trials after completion of enrollment into KRd+ASCT and after completion of KRd w/o ASCT (median follow-up [f/u] 4 years) as a historical control.
Methods Both studies enrolled patients (pts) with NDMM based on similar eligibility criteria except KRd+ASCT excluded transplant ineligible pts. The treatment schemas were generally similar between studies. In KRd+ASCT, pts received: four 28-day cycles of induction with CFZ IV 36 mg/m2 on Days (D) 1-2, 8-9, 15-16 (CFZ 20 mg/m2 for D1-2, C1 only), LEN PO D121 at 25 mg, DEX PO 40 mg/wk; followed by stem cell collection (SCC), melphalan 200 mg/m2 and ASCT; then KRd consolidation (C5-8) using the same doses and schedule except LEN 15 mg in C5 with the option to escalate to prior dose, and DEX reduced to 20 mg/wk; then KRd maintenance (C9-18) using the same doses as in C8 except CFZ on Days 1-2, 15-16 only. In KRd w/o ASCT, transplant-eligible pts underwent SCC after C4 then resumed KRd, and KRd maintenance was longer (C9-24). Both studies recommended single-agent LEN off study. The primary endpoint in KRd+ASCT is sCR at the end of C8. We hypothesized that an improvement of sCR from 30% at the end of C8 (historical KRd w/o ASCT) to >50% (KRd+ASCT) represents added benefit of ASCT with 5% type I error (2 sided) and supports further evaluation. Minimal residual disease (MRD) is evaluated by 10-color multiparameter flow cytometry (MFC, threshold 10-4-10‑5) and by next-generation sequencing (NGS, LymphoSIGHTTM, threshold at 10-6 for MRD negativity).
Results The current KRd+ASCT study enrolled 76 pts with 72 evaluable. Baseline characteristics were comparable between the KRd+ASCT and KRd w/o ASCT study populations, including median age (59 and 59y) and high-risk IMWG cytogenetics (36% and 33%). In the ongoing KRd+ASCT, 69 pts proceeded to ASCT at data cut-off (Jan 1, 2016), 50 completed KRd consolidation, and 26 KRd maintenance, with remaining pts on treatment, except 1 patient who progressed prior to transplant. At the end of C8, sCR was 72% for KRd+ASCT (n=50) vs 30% for KRd w/o ASCT (n=44) and 88% (n=26) vs 51% (n=41) at the end of C18. At median f/u of 17.8 months, 2-year PFS was 99% for KRd+ASCT vs 92% for KRd w/o ASCT at median f/u of 47.5 months. In KRd+ASCT, MRD by MFC was negative in 94% of pts tested (n=31) at the end of C8 and 95% of pts tested (n=19) at the end of C18. In KRd w/o ASCT, 4-year PFS was 69% overall, 78% in MRD-negative pts vs 60% in positive/unknown pts by MFC, and 100% in pts with MRD negative status by NGS. Updated MRD analyses and outcomes based on MRD status by both MFC and NGS will be presented at the meeting. The types and rates of adverse events (AEs) pre- and post-ASCT were comparable to AEs in KRd w/o ASCT.
Conclusion Recognizing limitations of cross-study comparisons, KRd+ASCT shows superior outcomes vs historical KRd w/o ASCT, supporting further evaluation in the randomized setting. Both KRd studies compare favorably to other NDMM studies.
By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS). USER TERMS AND CONDITIONS | PRIVACY POLICY
Cookie Settings Accept Terms & all Cookies
Anonymous User Privacy Preferences
Strictly Necessary Cookies (Always Active)
MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.
Performance Cookies
Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.
Google Analytics and Google Tag Manager embedded tracking functionalities are used for user behavior tracking/reporting. Google Analytics works in parallel and independently from MLG's features. Google Analytics relies on cookies and these cookies can be used by Google to track users across different platforms/services.