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Dr. Tomer Mark - Sequence impact of pomalidomide and carfilzomib on treatment response in relapsed MM

Tomer Mark, MD
Assistant Professor of Medicine
Division of Hematology and Oncology
Weill Cornell Medical College
New York, NY, USA

12.17.13

Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I

Saturday, December 7, 2013, 5:30 PM-7:30 PM, Hall G (Ernest N. Morial Convention Center)

Tomer M Mark, MD, MSc1, John N. Allan, MD1, Angelique Boyer1*, Adriana C Rossi, MD1*, Roger N Pearse, MD, PhD1*, Faiza Zafar, PA1*, Karen Pekle, NP1*, Linda Tegnestam, RN1*, David Jayabalan, B.S.M.S2*, Morton Coleman, MD3* and Ruben Niesvizky, MD1

1Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY
2Pathology, Weill Cornell Medical College, New York, NY
3Hematology and Oncology, Weill Cornell Medical College, New York, NY

Background:  Pomalidomide and Carfilzomib (Cfz) are two recently approved agents for the treatment of multiple myeloma (MM) that has relapsed after prior therapy including an IMiD and bortezomib. The sequencing of these agents to achieve maximum tumor reduction is thus far not known. We have previously reported response data from the combination clarithromycin, pomalidomide, dexamethasone (ClaPD) for relapsed or refractory MM. (Mark et al, ASH 2012). We examined the subset of these patients that had received a Cfz-based regimen prior to ClaPD as well as the subset of patients that received a Cfz-based regimen after ClaPD to determine whether the sequence of agents had any impact on response.

Methods: One hundred nineteen patients with heavily pretreated RRMM were enrolled into a single-institution study to investigate the effectiveness and tolerability of ClaPD. Eligible subjects had at least 3 prior lines of therapy, one line of which must have included lenalidomide. ClaPD is clarithromycin 500mg twice daily; pomalidomide 4mg for days 1-21, and dexamethasone 40mg on days 1,8,15,22 of a 28-day cycle. Two subsets of patients were compared: 1) Subjects that had received treatment with a Cfz-based prior to ClaPD (CP) and 2) Subjects that had received a Cfz-based therapy after progression on ClaPD (PC). Disease response evaluation was performed monthly with immunoelectrophoresis and free light chain analysis; bone marrow biopsy with skeletal imaging was used to confirm MM progression or complete response (CR).

Results: Fourteen patients comprised CP and 20 in PC.  Patients in the CP group were more heavily pre-treated with a median of 6 (range 3-15) lines of therapy, as compared to 5 lines (range 3-10) for PC. Responses are shown in Table 1. Median cycles of ClaPD and Cfz received in PC was 6.5 (range 2-16) and 5 (1-14), respectively. Median cycles of Cfz and ClaPD in the CP group was 8 (1-19) and 5 (1-23), respectively.

Table 1:

 

 

CP (n=14)

 

PC (n=20)

 

 

 

% response to Cfz

 

% response to Pom

 

% response to Pom

 

% response to Cfz

 

CR

 

0

 

0

 

5

 

0

 

VGPR

 

7

 

14

 

10

 

0

 

PR

 

64

 

28

 

45

 

40

 

SD

 

14

 

28

 

25

 

40

 

PD

 

14

 

28

 

15

 

20

 

ORR

 

71

 

42

 

60

 

40

 

³VGPR

 

7

 

14

 

15

 

0

 

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

Conclusions: ClaPD and a Cfz-based regimen appear to have equally effective response regardless of sequence in salvage chemotherapy.  Somewhat deeper responses are seen with ClaPD after Cfz as compared to Cfz after ClaPD, which is intriguing given that the CP group had more prior lines of treatment than PC.  Longer follow-up to analyze duration of the response is needed prior to concluding which sequence (PC vs CP) is more effective. This data supports the use of pomalidomide after carfilzomib failure and vice-versa as potent salvage therapeutic options.


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