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ASH 2011: Dr. Palumbo - A Phase I/II Study of Pomalidomide-Cyclophosphamide-Prednisone (PCP) in Patients with Multiple Myeloma Relapsed/Refractory to Lenalidomide
Antonio Palumbo, MD
University of Torino
AOU S. Giovanni Battista
Torino, Italy
12.07.11

Background: Patients with multiple myeloma (MM) relapsed/refractory after immunomodulatory drugs and bortezomib have limited treatment options. Recently, the combination pomalidomide-dexamethasone has led to at least partial response (PR) of 25-42% in relapsed/refractory MM and 32% in patients refractory to lenalidomide.

Aims: In this study we evaluate the safety and efficacy of the combination pomalidomide-cyclophosphamide-prednisone (PCP) in patients with MM who received 1-3 lines of treatment and were relapsed/refractory to lenalidomide therapy.

Methods: Between August 2010 and July 2011, 41 patients were enrolled; median age was 69 years (range 49-82); 23 patients relapsed after lenalidomide and 18 patients were refractory to lenalidomide. The first 24 patients entered the phase I of the study to define the maximum tolerated dose (MTD) of PCP: 4 dose levels of pomalidomide (1, 1.5, 2 and 2.5 mg/day, days 1-28) were tested in combination with cyclophosphamide (50 mg every other day, days 1-28) and prednisone (50 mg every other day, days 1-28) for six 28-day cycles. Thromboprophylaxis with aspirin (100 mg/day) was recommended, low-molecular weight heparin was given to high risk patients. Dose Limiting Toxicities (DLTs) were defined as: grade 4 neutropenia for more than 3 days, grade 4 thrombocytopenia, grade 3-4 neutropenic fever, any grade 3-4 non-hematologic toxicity. The MTD was achieved when 25% of patients experienced a DLT, using the Bayesian Continual Reassessment Method. In the phase II of the study, the Simon two-stage design was used and 17 additional patients were enrolled and received the MTD of pomalidomide.

Results: DLTs occurred in 1/4 patient who received pomalidomide 1.5 mg (grade 4 thrombocytopenia) and in 3/12 patients who received pomalidomide 2.5 mg (grade 3 neuropathy, grade 3 hepatic toxicity and grade 4 thrombocytopenia). The MTD was defined at 2.5 mg/day, with an estimated DLT probability of 0.258 (95% credibility interval: 0.101-0.468). 32 patients received at least one cycle of therapy and could be evaluated for efficacy and safety. At least PR was reported in 19/32 (59%) patients, including 2 complete response (CR), 5 very good partial response (VGPR), 12  PR. In patients refractory to lenalidomide, at least PR was reported in 11/15 (73%) patients, including 1 CR, 2 VGPR, 8 PR. Grade 4 hematologic toxicities were neutropenia (9%) and thrombocytopenia (9%). Grade 3-4 non-hematologic toxicity included infection (9%), rash (9%), neurologic (6%) and hepatic (3%) toxicities. Thromboembolism occurred in 1 patient.

Conclusions: At least PR was achieved in 73% of patients refractory to lenalidomide; grade 4 neutropenia and/or thrombocytopenia were less than 10%. The combination pomalidomide (2.5 mg/day), cyclophosphamide (50 mg every other day), prednisone (50 mg every other day) showed high response rates with limited toxicities in patients relapsed/refractory to lenalidomide. Updated data will be presented at the meeting.

 

 

All relapsed/refractory patients who received at least 1 course

(N=32)

 

Refractory patients

(N=15)

Best response (%)

 

 

≥PR

59

73

CR

6

7

VGPR

16

13

PR

37.5

53

SD

37.5

27

PD

3

0

Grade 4 neutropenia (%)

9

7

Grade 4 thrombocytopenia (%)

9

7

PR: partial response; CR: complete response; VGPR: very good partial response; SD: stable disease; PD: progressive disease

Disclosures: Palumbo: Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Larocca: Janssen-Cilag: Honoraria. Guglielmelli: Janssen-Cilag: Honoraria; Celgene: Honoraria. Giuliani: Celgene: Research Funding; Novartis: Research Funding. Boccadoro: Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding.


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