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3271 Pomalidomide + Low-Dose Dexamethasone + Daratumumab in Relapsed and/or Refractory Multiple Myeloma after Lenalidomide-Based Treatment Failure

Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster II
Hematology Disease Topics & Pathways:
Diseases, multiple myeloma, Adult, Plasma Cell Disorders, Study Population, Lymphoid Malignancies, Clinically relevant
Sunday, December 2, 2018, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

David S Siegel, MD, PhD1, Gary J. Schiller, MD2, Christy J. Samaras, DO3, Michael Sebag, MD, PhD4, Jesus G. Berdeja, MD5, Siddhartha Ganguly, MD6*, Jeffrey V Matous, MD7, Kevin Song, MD8, Christopher S. Seet, MD9, Giampaolo Talamo10*, Mirelis Acosta-Rivera11*, Michael Bar12*, Donald P. Quick, MD13, Bertrand Anz, MD14*, Gustavo Fonseca15*, Donna Reece16*, Amit Agarwal, MD, PhD17, Weiyuan Chung17*, Faiza Zafar, MPAS17* and Nizar Bahlis, MD18

1John Theurer Cancer Center, Myeloma and Lymphoma Divisions, Hackensack University Medical Center, Hackensack, NJ
2David Geffen School of Medicine at UCLA, Los Angeles, CA
3Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
4McGill University Health Centre, Montreal, QC, Canada
5Sarah Cannon Research Institute, Nashville, TN
6The University of Kansas Cancer Center, Fairway, KS
7Colorado Blood Cancer Institute, Denver, CO
8The Vancouver General Hospital, Vancouver, BC, CAN
9UCLA Medical Center, Los Angeles, CA
10Penn State Hershey Cancer Institute, Hershey, PA
11Fundacion de Investigacion, San Juan, Puerto Rico
12Stamford Hospital, Stamford, CT
13Joe Arrington Cancer Research Treatment Center, Lubbock, TX
14Tennessee Oncology, Chattanooga, TN
15Florida Cancer Specialists, St. Petersburg, FL
16Princess Margaret Cancer Centre, Toronto, Canada
17Celgene Corporation, Summit, NJ
18University of Calgary, Calgary, AB, Canada

BACKGROUND

Lenalidomide (LEN) until progressive disease (PD) is an established treatment (Tx) in newly diagnosed and relapsed and/or refractory multiple myeloma (RRMM); thus, patients (pts) for whom the benefit of LEN has been exhausted are a clinically relevant population. However, LEN-refractory pts have typically been excluded from recent clinical trials investigating triplet regimens after ≤ 3 prior Tx lines. MM-014 (NCT01946477) is an ongoing phase 2 study that was designed to assess the safety and efficacy of pomalidomide (POM)-based Tx regimens in pts with RRMM and first- or second-line LEN Tx failure immediately before study entry. Earlier results from cohort A (POM + low-dose dexamethasone [LoDEX]) and cohort B (POM + LoDEX + daratumumab [DARA]) indicate that POM-based Tx is safe and effective in this setting. Here we report updated results from cohort B.

METHODS

Eligible pts had RRMM, had 1 or 2 prior lines of Tx, received LEN-based Tx as their most recent Tx regimen, and had PD during or after their last line of Tx. Pts received POM 4 mg/day on days 1 through 21 + LoDEX 40 mg/day (20 mg/day if aged > 75 years) on days 1, 8, 15, and 22 and DARA 16 mg/kg intravenously on DEX dosing days of cycles 1 and 2, days 1 and 15 of cycles 3 through 6, then day 1 of cycle 7 and beyond. Each Tx cycle lasted 28 days. Thromboprophylaxis was mandatory. The primary endpoint for cohort B is overall response rate (ORR) by modified International Myeloma Working Group criteria. Secondary endpoints include time to response (TTR), progression-free survival (PFS), time to progression (TTP), and safety.

RESULTS

The intention-to-treat (ITT) population comprised 112 pts (median follow-up, 8.2 mos); data cutoff was April 30, 2018. Median age was 66.5 years, 67.9% of pts were male, and 111 (99.1%) had ECOG PS ≤ 1. A total of 34 pts discontinued Tx: 19 due to PD, 9 due to study withdrawal, 2 due to adverse events (AEs), and 4 due to other reasons. All pts received prior LEN, and 87 (77.7%) received prior bortezomib; 84 pts (75.0%) were refractory to LEN, while 28 (25.0%) relapsed after LEN-based Tx. Median duration of the most recent prior LEN-based Tx was 23.9 mos, with 36 pts (32.1%) receiving LEN 25 mg/day during their last LEN-based Tx.

ORR was 77.7%, with 33.9% of pts achieving ≥ very good partial response. Median TTR was 1.0 mo. The clinical benefit rate (≥ minimal response [MR]) was 85.7%. ORR was 80.6% in the efficacy-evaluable population (n = 108; defined as all pts who received ≥ 1 dose of study drug and had ≥ 1 post-baseline response assessment), 75.0% in LEN-refractory pts, and 76.2% in pts with 2 prior lines of Tx (n = 42). The 9-mo PFS rate was 86.3% (range, 76.5%-92.2%); median PFS was not estimable (NE; Figure). The 9-mo TTP rate was 88.1% (range, 78.3%-93.6%); median TTP was NE.

The most common grade 3/4 hematologic treatment-emergent AE (TEAE) in the safety population (n = 112) was neutropenia (61.6%; Table); pneumonia was the most common grade 3/4 nonhematologic TEAE (7.1%). POM dose reductions occurred in 31 pts (27.7%); per protocol, DARA dose reductions were not allowed. POM dose interruptions due to AEs were reported in 69 pts (61.6%) and DARA dose interruptions due to AEs were reported in 82 pts (73.2%). POM and DARA dose interruptions due to neutropenia were reported in 39 (34.8%) and 42 (37.5%) pts, respectively; 25 pts (22.3%) had DARA dose interruptions due to infusion-related reactions. Median durations of POM and DARA Tx were 6.0 mos (range, 0.3-17.7 mos) and 6.6 mos (range, 0.3-18.6 mos), respectively; among those who achieved ≥ MR, pts remained on POM Tx for a median of 7.4 mos (range, 0.9-17.7 mos) and on DARA Tx for a median of 7.5 mos (range, 0.9-18.6 mos).

CONCLUSIONS

LEN-refractory pts with RRMM are in need of effective Tx options. MM-014 is the first prospective clinical trial to investigate a POM-based doublet or triplet regimen immediately after LEN-based Tx failure. In the context of a relatively short follow-up, the 9-mo PFS rate (86.3%) is promising. The ORR (77.7%) was higher than that previously reported with this triplet combination in heavily pre-treated pts with RRMM (≥ 2 prior lines [median, 4]; ORR, 60%), and the rate of grade 3/4 neutropenia in the present study was lower (61.6% vs 77%). These updated results from cohort B continue to demonstrate that POM + LoDEX + DARA is safe and effective following first- or second-line LEN-based Tx failure and further support earlier use of POM-based Tx in pts with RRMM

Disclosures: Siegel: Takeda: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Merck: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau. Schiller: Pharmacyclics: Research Funding; Celator/Jazz Pharmaceuticals: Research Funding. Sebag: Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees; Janssen Inc.: Membership on an entity's Board of Directors or advisory committees; Celgene Canada: Membership on an entity's Board of Directors or advisory committees. Berdeja: Bluebird: Research Funding; Janssen: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Bristol-Myers Squibb: Research Funding; Glenmark: Research Funding; Genentech: Research Funding; Amgen: Research Funding; Teva: Research Funding; Poseida Therapeutics, Inc.: Research Funding. Ganguly: Janssen: Consultancy; Seattle Genetics: Speakers Bureau; Amgen: Consultancy; Daiichi Sankyo: Research Funding. Matous: Celgene: Consultancy, Honoraria, Speakers Bureau. Bar: Celgene: Consultancy. Quick: CTI BioPharma: Research Funding. Fonseca: Celgene: Speakers Bureau. Reece: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Merck: Honoraria, Research Funding; Otsuka: Research Funding. Agarwal: Celgene Corporation: Employment, Equity Ownership. Chung: Celgene Corporation: Employment, Equity Ownership. Zafar: Celgene: Employment. Bahlis: Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding.

*signifies non-member of ASH