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Attend this session at the
2017 ASCO Annual Meeting!


Session: Hematologic Malignancies—Plasma Cell Dyscrasia

Type: Poster Session

Time: Monday June 5, 8:00 AM to 11:30 AM

Location: Hall A


Session: Hematologic Malignancies—Plasma Cell Dyscrasia

Type: Poster Discussion Session

Time: Monday June 5, 3:00 PM to 4:15 PM

Location: E354b

Carfilzomib-associated cardiovascular adverse events: A systematic review and meta-analysis.

Sub-category:
Multiple Myeloma

Category:
Hematologic Malignancies—Plasma Cell Dyscrasia

Meeting:
2017 ASCO Annual Meeting

Abstract No:
8018

Poster Board Number:
Poster Discussion Session (Board #344)

Citation:
J Clin Oncol 35, 2017 (suppl; abstr 8018)

Author(s): Adam Justin Waxman, Suparna Chandra Clasen, Alfred L. Garfall, Joseph R. Carver, Dan T. Vogl, Rupal O'Quinn, Adam D. Cohen, Edward Allen Stadtmauer, Bonnie Ky, Brendan M. Weiss; Abramson Cancer Center, Philadelphia, PA; University of Pennsylvania Division of Cardiology, Philadelphia, PA; Hospital of the University of Pennsylvania, Philadelphia, PA

Abstract Disclosures

Abstract:

Background: The incidence and nature of cardiovascular adverse events (CVAEs) with carfilzomib (CFZ) in multiple myeloma (MM) remain incompletely defined. We performed the first systematic review and meta-analysis of CFZ CVAEs. Methods: PubMed was queried for the keywords “carfilzomib,”“Kyprolis,” and “PX-171.” Phase 1-3 clinical trials of carfilzomib in MM with evaluable toxicity data were included. CVAEs were defined as heart failure, hypertension, ischemia, and arrhythmia. All-grade and grade ≥3 CVAEs and study characteristics were recorded. Summary incidence rates and relative risks (for randomized trials) with 95% confidence intervals were calculated using the logistic-normal random-effects model. Subgroup analyses were performed using study level covariates. Results: 514 studies were reviewed. 2623 MM patients from 25 eligible studies were included. Incidence rates are summarized in the table. All grade and grade ≥3 CVAEs were seen in 16.8% and 7.6 %, respectively. Phase 2 or 3 studies, carfilzomib doses ≥45mg/m2, and longer infusion length were study characteristics associated with high-grade cardiac AEs (p<0.05). Median age >65, prior MM therapies, and concurrent MM therapies were not associated with CVAEs (p>.05). For the three randomized trials, the relative risk of all-grade and grade ≥3 CVAEs were 1.75 and 2.25, respectively (p<0.001). Conclusions: CFZ is associated with a significant incidence of CVAEs, including heart failure, hypertension, ischemia, and arrhythmia. Phase I studies may be underdetecting CVAEs. Future studies are needed to: identify patients at high-risk for CVAEs, develop optimal monitoring strategies, and explore therapies to mitigate these risks.

Adverse EventAll-Grade Incidence % (95% CI)p-valueGrade ≥3 Incidence % (95% CI)p-value
Any Cardiac16.8 (11.9-22.3)<0.0017.6 (5.4-10.1)<0.001
Heart Failure4.1 (2.3-6.3)<0.0012.6 (1.5-3.8)<0.001
Hypertension12.2 (9.7-14.9)<0.0014.3 (2.6-6.4)<0.001
Ischemia1.4 (0.4-2.8)<0.0010.8 (0.4-1.4)<0.001
Arrhythmia2.5 (0.4-5.7)0.0020.6 (0.1-1.5)0.007
Cardiac Arrest----0.0 (0.0-0.2)0.983

 
Other Abstracts in this Sub-Category:

 

1. Daratumumab (DARA) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients (pts) with newly diagnosed multiple myeloma (MMY1001): An open-label, phase 1b study.

Meeting: 2017 ASCO Annual Meeting Abstract No: 8000 First Author: Andrzej J. Jakubowiak
Category: Hematologic Malignancies—Plasma Cell Dyscrasia - Multiple Myeloma

 

2. Lenalidomide, doxorubicin hydrochloride and dexamethasone versus bortezomib, lenalidomide, and dexamethasone prior to scheduled stem cell transplant in newly diagnosed myeloma.

Meeting: 2017 ASCO Annual Meeting Abstract No: 8001 First Author: Stefan Knop
Category: Hematologic Malignancies—Plasma Cell Dyscrasia - Multiple Myeloma

 

3. An open-label, single arm, phase IIa study of bortezomib, lenalidomide, dexamethasone, and elotuzumab in newly diagnosed multiple myeloma.

Meeting: 2017 ASCO Annual Meeting Abstract No: 8002 First Author: Jacob Laubach
Category: Hematologic Malignancies—Plasma Cell Dyscrasia - Multiple Myeloma

 

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