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508 Open-Label, Multicenter, Phase 1b Study of Daratumumab in Combination with Pomalidomide and Dexamethasone in Patients with at Least 2 Lines of Prior Therapy and Relapsed or Relapsed and Refractory Multiple Myeloma

Myeloma: Therapy, excluding Transplantation
Program: Oral and Poster Abstracts
Type: Oral
Session: 653. Myeloma: Therapy, excluding Transplantation: Novel Combinations in Immuno-Oncology
Monday, December 7, 2015: 7:45 AM
Hall E1, Level 2 (Orange County Convention Center)

Ajai Chari, MD1, Sagar Lonial, MD2,3, Attaya Suvannasankha4, Joseph W. Fay5, Bertrand Arnulf6*, Jainulabdeen J. Ifthikharuddin7, Xiang Qin8*, Tara Masterson8*, Kerri Nottage9*, Jordan M Schecter9*, Tahamtan Ahmadi8*, Brendan Weiss10*, Amrita Krishnan11 and Suzanne Lentzsch12

1Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY
2Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA
3Winship Cancer Institute of Emory University, Department of Hematology and Medical Oncology, Atlanta, GA
4Indiana University School of Medicine and Simon Cancer Center, Richard L. Roudebush VAMC, Indianapolis, IN
5Baylor Institute for Immunology Research, Dallas, TX
6Hôpital Saint Louis, Paris, France
7James P. Wilmot Cancer Center, University of Rochester Strong Memorial Hospital, Rochester, NY
8Janssen Research & Development, LLC, Spring House, PA
9Janssen Research & Development, LLC, Raritan, NJ
10Abramson Cancer Center and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
11City of Hope, Duarte, CA
12Columbia University Medical Center, New York, NY

Introduction: Daratumumab (DARA) is a human anti-CD38 IgG1κ monoclonal antibody with remarkable safety and activity as monotherapy in heavily treated relapsed and refractory (RR) multiple myeloma (MM) (Lokhorst HM. J Clin Oncol 2014;32 Suppl:abstr 8513. Lonial S. J Clin Oncol 2015;33 Suppl:abstr LBA8512). DARA has demonstrated clinical activity in combination with lenalidomide (LEN) and dexamethasone (D) in relapsed or RR MM (Plesner T. Blood 2014;124(21):84). This ongoing 4-arm, multicenter, phase 1b study (NCT01998971) evaluated the safety and efficacy of DARA in combination with various backbone therapies and pomalidomide plus D (POM-D). Results in newly diagnosed patients treated with DARA and backbone therapies were previously reported (Mateos MV, et al. Haematologica 2015;100(s1):84).

Methods: Patients in the DARA + POM-D arm had relapsed or RR MM with ≥2 prior lines of therapy including ≥2 consecutive cycles of LEN and bortezomib. During 28-day treatment cycles patients received DARA 16 mg/kg qw for 2 cycles, then q2w for 4 cycles, and q4w until disease progression (PD). Pomalidomide 4 mg was administered qd for 21 days with D 40 mg qw (20 mg for patients >75 years of age). The primary endpoint was safety and tolerability of DARA in combination with POM-D. Overall response rate (ORR) was a secondary endpoint. Disease responses were evaluated by an independent data safety monitoring board.

Results: A total of 77 patients were enrolled into the DARA + POM-D arm. The median (range) age was 64 (35-86) years and the median number of prior therapies was 3.5 (2-10). Sixty-five percent of the patients were refractory to bortezomib, 30% to carfilzomib, 88% to lenalidomide, and 65% to both a PI and IMiD.

With a median (range) duration of follow-up of 72 (1-423) days, 28 (36%) patients have discontinued treatment due to PD (15 [20%]), adverse events (AEs; 6 [8%]), death or physician’s decision (3 [4%] each), and one (1%) patient withdrawal. The median (range) duration of treatment was 69 days (1-416), and the median (range) number of infusions was 7.5 (1-25). Forty-nine (64%) patients continue on study treatment and enrollment is ongoing.

There was little additional toxicity when DARA was added to POM-D other than DARA-specific infusion related reactions (IRRs; 47/77 patients). Most occurred on Cycle 1 Day 1 (45/47 patients), and the most common (>10%) IRRs were chills (13%), cough (13%), and dyspnea (11%). The most common (>10%) and grade ≥3 adverse events (AEs) are presented in Table 1. Five patients died within 30 days of receiving study treatment due to AEs (4[5%]) or progressive disease (1 [1%]).

In 53 patients with >1 post-baseline assessment, the ORR was 58.5%, with 3 stringent complete responses (sCR), 1 complete response (CR), 12 very good partial responses (VGPR), 15 partial responses (PR), 2 minimal responses, 18 stable disease, and 2 PD. Many responses deepened over time. Median (range) time to first response was 30 (28-92) days. After a median follow-up of 148 days, 4 out of 31 responders developed PD. Among the evaluable double refractory patients (n = 40), there was 1 sCR, 1 CR, 10 VGPRs, and 11 PRs with an ORR of 57.5%.

Conclusions: The addition of DARA to POM-D was well tolerated and did not result in additional toxicities with the exception of DARA-related infusion reactions. Deep and durable responses were observed quickly, along with a high response rate. Study enrollment is ongoing and data will be updated at the meeting.

Table 1. Most Common (>10%) Adverse Events (N = 77)

Adverse Event, n (%)

Any Grade

Grade ≥3

Neutropenia

42 (54.5%)

39 (50.6%)

Anemia

28 (36.4%)

16 (20.8%)

Fatigue

28 (36.4%)

4 (5.2%)

Cough

24 (31.2%)

0

Nausea

21 (27.3%)

0

Dyspnea

20 (26.0%)

5 (6.5%)

Diarrhea

19 (24.7%)

1 (1.3%)

Leukopenia

19 (24.7%)

12 (15.6%)

Thrombocytopenia

17 (22.1%)

8 (10.4%)

Pyrexia

16 (20.8%)

1 (1.3%)

Dizziness

15 (19.5%)

0

Chills

14 (18.2%)

0

Nasal Congestion

14 (18.2%)

0

Upper Respiratory Tract Infection

14 (18.2%)

1 (1.3%)

Back Pain

13 (16.9%)

2 (2.6%)

Constipation

13 (16.9%)

0

Tremor

13 (16.9%)

2 (2.6%)

Insomnia

12 (15.6%)

1 (1.3%)

Lymphopenia

11 (14.3%)

7 (9.1%)

Muscle Spasms

11 (14.3%)

0

Vomiting

11 (14.3%)

0

Arthralgia

9 (11.7%)

1 (1.3%)

Pruritus

9 (11.7%)

0

Throat Irritation

9 (11.7%)

0

Anxiety

8 (10.4%)

0

Headache

8 (10.4%)

0

Hypertension

8 (10.4%)

4 (5.2%)

Musculoskeletal Chest Pain

8 (10.4%)

2 (2.6%)

Peripheral Edema

8 (10.4%)

1 (1.3%)

Disclosures: Chari: Celgene: Consultancy , Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Millennium/Takeda: Consultancy , Research Funding ; Array Biopharma: Consultancy , Other: Institutional Research Funding , Research Funding ; Novartis: Consultancy , Research Funding ; Biotest: Other: Institutional Research Funding ; Onyx: Consultancy , Research Funding . Lonial: Janssen: Consultancy , Research Funding ; Onyx: Consultancy , Research Funding ; Novartis: Consultancy , Research Funding ; Bristol-Myers Squibb: Consultancy , Research Funding ; Janssen: Consultancy , Research Funding ; Onyx: Consultancy , Research Funding ; Celgene: Consultancy , Research Funding ; Millennium: Consultancy , Research Funding . Suvannasankha: Celgene: Honoraria , Research Funding ; Onyx: Honoraria , Research Funding . Arnulf: Janssen: Membership on an entity’s Board of Directors or advisory committees ; Celgene: Membership on an entity’s Board of Directors or advisory committees . Qin: Janssen: Employment . Masterson: Janssen: Employment . Nottage: Janssen: Employment . Schecter: Janssen: Employment . Ahmadi: Janssen: Employment . Weiss: Janssen and Millennium: Consultancy ; Janssen and Onclave: Research Funding . Krishnan: Millenium: Speakers Bureau ; BMS: Consultancy ; Jazz: Consultancy ; Janssen: Consultancy ; Onyx: Speakers Bureau ; Celgene: Consultancy , Speakers Bureau . Lentzsch: Celgene: Consultancy ; Janssen: Consultancy ; Axiom: Honoraria ; Novartis: Consultancy ; BMS: Consultancy .

*signifies non-member of ASH