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413 A Randomized Phase II, Open Label, Study of Daratumumab, Weekly Low-Dose Oral Dexamethasone and Cyclophosphamide with or without Pomalidomide in Patients with Relapsed and Refractory Multiple MyelomaClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Relapsed/Refractory Multiple Myeloma
Hematology Disease Topics & Pathways:
multiple myeloma, Diseases, Plasma Cell Disorders, Lymphoid Malignancies
Sunday, December 6, 2020: 12:15 PM

Michael Sebag, MD, PhD1, Nizar Bahlis, MD2, Christopher P. Venner, MD3, Arleigh McCurdy, MD, BSc4, C. Tom Kouroukis, MD, MSc, FRCPC5, Jesse Shustik, MD6, Rami Kotb, MD7*, Darrell J White, MD8, Julie Stakiw, MD9, Nicole B. Laferriere, MD, PhD10,11, Anthony Reiman, MD12*, Fernando Camacho, PhD13*, Molei Fu13*, Engin Gul, BSc14* and Donna E. Reece, MD15,16

1Division of Hematology, McGill University Health Centre, Montreal, QC, Canada
2Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada
3Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
4Department of Medicine, Division of Hematology, The Ottawa Hospital, Ottawa, ON, Canada
5Juravinski Cancer Centre, Hamilton, ON, Canada
6BC Cancer Agency, Surrey, BC, CAN
7Cancer Care Manitoba, Winnipeg, MB, Canada
8Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada
9Saskatoon Cancer Centre, Saskatoon, SK, Canada
10NWORCC, Thunder Bay, ON, CAN
11Thunder Bay Regional Health Sciences, Thunder Bay, ON, Canada
12University of New Brunswick, Saint John Regional Hospital, Saint John, NB, CAN
13Canadian Myeloma Research Group (formerly MCRN), Vaughan, ON, Canada
14University Health Network-PMH, Concord, ON, Canada
15Canadian Myeloma Research Group (formerly MCRN), Toronto, Canada
16Princess Margaret Cancer Centre, Toronto, ON, Canada

Lenalidomide (Len) has become the standard first line therapeutic choices for Multiple Myeloma (MM), whether as first line for transplant ineligible patients or as maintenance post transplant. Therapies that are designed to overcome lenalidomide refractory disease are few and often give disappointing results. We previously reported the efficacy of daratumumab in combination with low dose weekly cyclophosphamide and dexamethasone with and without pomalidomide (Pom). In patients previously treated with both Proteosome Inhibitors (PIs) and Len the combination of Dara, Cyclophosphamide, Dex and pomalidomide (DCdP) produced impressive response rates. Although the same combination without the Pom had appreciably lower response rates and initial progression free survival (PFS), most patients were salvageable after the addition of Pom. Here we report an update on this trial.


In this phase II clinical trial, 120 patients with relapsed refractory MM, after at least one line of therapy, were randomized to receive either daratumumab (16mg/kg) weekly IV C1-2, every 2 weeks C3-6, monthly C7+, dexamethasone 40mg po weekly, cyclophosphamide 400mg po weekly and pomalidomide 4mg po days 1-21 of 28 day cycles (Arm A) or the same doses and dosing regimen of daratumumab, cyclophosphamide and dexamethasone but with Pom added only after confirmed disease progression (Arm B). All patients were exposed to PIs and Len prior to study entry. The primary endpoint of this study was the comparison of the PFS of Arm A to that of Arm B after the addition Pom (PFS2) at 36 months while secondary endpoints included overall responses, duration of responses, survival and safety. Correlative laboratory studies will be reported separately.


As of 1 June 2020 all 120 patients have been enrolled in 11 sites across Canada. The patient characteristics were: median age 65 (range 39-82); median 2 prior lines of therapy (range 1-8); 70% had a previous ASCT; 95% Len exposed; 93% PI exposed; 90% Len and PI exposed; 25% carfilzomib exposed, Len was the last line of therapy in 65%. Median follow-up was 19 months (range 1-28), median number of cycles 16 (range 1-31). The overall response rates (ORR) were 88.6% for arm A compared with 50.8% for arm B, with 62.4% and 28.8% of patients achieving ≥VGPR in arm A and B respectively. 43 patients in Arm B have progressed by data cut-off and the ORR after adding pomalidomide was 55.8% with a median follow up time 6.6 months. The response rates for both Arm A and B (prior to Pom) did not vary much in patients in whom Len was the last line of therapy (94.5% vs 55.7%), compared to the ITT population. The response rate after the addition of Pom to Arm B patients after first progression was also similar in patients in whom Len was used last (58.3%). The median PFS of Arm A was an impressive 20.5 months (regardless of previous Len exposure) while it was considerably shorter for Arm B prior to addition of Pom at 11.5 months and 16.7 months overall after addition of Pom. Median OS has not yet been reached, however, time to subsequent therapies from randomization was similar in both groups at 18.1 (Arm A) and 20.2 months (Arm B).

Rates of grade 3/4 hematologic toxicities included a high incidence of neutropenia, 85.2% in Arm A and 50.8% in Arm B overall; however, the rates of febrile neutropenia were low at 13.1% and 16.9% respectively. The most common infection was pneumonia, seen in 13% of Arm A and 6.8% of Arm B prior to Pom and 20.3% overall for Arm B.


The results of this randomized phase II trial demonstrate that in a highly pretreated MM population (2 lines of therapy but range 1-8) that the four-drug combination (DCdP) confers impressive ORR (88.6%) and a median PFS (20.5 months) that compares favourably to other studies with anti-CD38 antibodies combined with Pomalidomide (11.5 months for Isatuximab-Pom-Dex, albeit in patients with 3 median lines of prior therapy). In Len exposed patients, DCdP demonstrates an ORR of 93% and a PFS of 20.5 months which is similar to what has been reported recently in Len exposed patients with Dara-pom-dex but after only one previous line of therapy. Although the 3 combination (DCd) showed an inferior initial response rate, over half of patients recaptured a response after the addition of Pom. Finally, while the overall PFS is lower in Arm B, the times to subsequent therapies are so far similar in both arms of this study opening a sequential-based approach as a feasible and economic option for further study.

Disclosures: Sebag: Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding. Bahlis: Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; BMS/Celgene and Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Genentech: Consultancy, Honoraria. Venner: Celgene, Amgen: Research Funding; Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria. McCurdy: Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Honoraria. Shustik: Celgene: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Kotb: Amgen: Honoraria; Celgene: Honoraria; Sanofi: Research Funding; Karyopharm: Current equity holder in publicly-traded company; Merck: Honoraria, Research Funding; Janssen: Honoraria; Takeda: Honoraria. White: Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Stakiw: BMS: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Roche: Research Funding; Lundbeck: Honoraria. Laferriere: Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Camacho: Janssen: Consultancy; AbbVie: Consultancy; Bausch-Health: Consultancy. Reece: Otsuka: Research Funding; Merck: Honoraria, Research Funding; Janssen, Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Janssen, Bristol-Myers Squibb, Amgen, Takeda: Consultancy, Honoraria.

*signifies non-member of ASH