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Clinical Trial
. 2023 Oct 10;7(19):5703-5712.
doi: 10.1182/bloodadvances.2022008866.

Phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone with and without daratumumab in relapsed multiple myeloma

Benjamin A Derman  1 , Jeffrey Zonder  2 , Donna Reece  3 , Craig Cole  4   5 , Jesus Berdeja  6 , Andrew T Stefka  1 , Ajay Major  1 , Andrew Kin  2 , Kent Griffith  5 , Jagoda Jasielec  1   7 , Andrzej J Jakubowiak  1
Affiliations
Clinical Trial

Phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone with and without daratumumab in relapsed multiple myeloma

Benjamin A Derman et al. Blood Adv. .

Abstract

We conducted a phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone (KPd) and KPd with daratumumab (Dara-KPd) in relapsed/refractory multiple myeloma. The primary end points were identification of a maximum tolerated dose (MTD) of KPd for phase 1, and rates of overall response (ORR) and near complete response (nCR) after 4 cycles of KPd and Dara-KPd, respectively, for phase 2. The MTD for KPd was carfilzomib 20/27 mg/m2 on days 1, 2, 8, 9, 15, and 16 (cycles 1-8) and days 1, 2, 15, and 16 for cycles 9 and beyond; oral pomalidomide 4 mg on days 1 to 21; and oral dexamethasone 40 mg weekly in 28-day cycles. Sixty-six patients received KPd, including 34 at the MTD. The ORR after 4 cycles of KPd at the MTD was 27/34 (79%; 95% confidence interval [CI], 62%-91%), meeting the statistical threshold for efficacy. At a median follow-up of 44 months, the median progression-free survival (PFS) was 13 months and overall survival (OS) 44 months. Twenty-eight patients received Dara-KPd. The rate of nCR or better after 4 cycles was 11/28 (39%; 95% CI, 22%-59%), meeting the statistical threshold for efficacy. As the best response to Dara-KPd, the ORR was 25/28 (89%) and the rate of measurable residual disease negativity by flow cytometry (10-5) was 17/26 (65%). At a median follow-up of 26 months, the median PFS and OS for Dara-KPd were not reached. Dara-KPd induced deeper and more durable responses than KPd without compromising safety in a predominantly high-risk, lenalidomide-refractory population, warranting further evaluation of this quadruplet. This trial is registered at www.clinicaltrials.gov as #NCT01665794.

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Conflict of interest statement

Conflict-of-interest disclosure: B.A.D. provided consultancy for Janssen, Sanofi, and COTA Healthcare, and received honoraria from Plexus Communications and MJH Life Sciences. J.Z. provided consultancy for Intellia, Amgen, Takeda, Janssen, Regeneron, Alnylam, Caelum, and Oncopeptides, and received research funding from Bristol Myers Squibb (BMS), and Celgene. D.R. provided consultancy for Janssen, BMS, Takeda, and Karyopharm; received honoraria from Janssen, BMS, Sanofi, Amgen, GlaxoSmithKline (GSK), and Takeda; and received research funding from BMS, Janssen, and Sanofi. C.C. provided consultancy for AstraZeneca, PRIME Education, Sanofi, and Oncopeptides, and received research funding from GSK. J.B. provided consultancy for AbbVie, Amgen, BioClinica, bluebird bio, BMS, Celgene, Celularity, Constellation, CRISPR Therapeutics, CURIS, Eli Lilly, EMD Sorono, Genentech, Glenmark, Ichnos, Janssen, Kesios, Legend, SecuraBio, and Servier, and received resarch funding from 2seventy bio, AbbVie, Acetylon, Amgen, bluebird bio, BMS, Celgene, Celularity, Constellation, CRISPR Therapeutics, Janssen, Karyopharm, Kite Pharma, Novartis, Poseida, Prothena, Sanofi, Takeda, and Teva. A.T.S. reports employment at SimBioSys. J.J. reports employment at Janssen. A.J.J. reports consultancy and advisory board membership for AbbVie, Adaptive, Amgen, BMS/Celgene, GSK, Janssen, Juno, and Karyopharm. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
CONSORT diagram. SAE, serious AE.
Figure 2.
Figure 2.
Response rates. Best response in the KPd and Dara-KPd cohorts. sCR, stringent complete response.
Figure 3.
Figure 3.
Progression free survival and overall survival. PFS (A) and OS (B) for the KPd cohort. PFS (C) and OS (D) for the Dara-KPd cohort. NR, not reached.
See this image and copyright information in PMC

References

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