POMALIDOMIDE, CYCLOPHOSPHAMIDE AND DEXAMETHASONE IN CASE OF SUBOPTIMAL RESPONSE TO POMALIDOMIDE AND DEXAMETHASONE IN RELAPSED AND REFRACTORY MULTIPLE MYELOMA: RESULTS OF THE GMMG-PERSPECTIVE TRIAL
Author(s): ,
Katja Weisel
Affiliations:
University Hospital of Tuebingen,Tuebingen,Germany
,
Hans Salwender
Affiliations:
Asklepios Clinic,Hamburg,Germany
,
Christof Scheid
Affiliations:
University of Cologne,Cologne,Germany
,
Manola Zago
Affiliations:
University Hospital of Tuebingen,Tuebingen,Germany
,
Britta Besemer
Affiliations:
University Hospital of Tuebingen,Tuebingen,Germany
,
Mathias Haenel
Affiliations:
Clinic of Chemnitz,Chemnitz,Germany
,
Jan Duerig
Affiliations:
University of Essen,Essen,Germany
,
Markus Munder
Affiliations:
University of Mainz,Mainz,Germany
,
Hans-Walter Lindemann
Affiliations:
Catholic Hospital Hagen,Hagen,Germany
,
Anja Seckinger
Affiliations:
University of Heidelberg,Heidelberg,Germany
,
Christina Kunz
Affiliations:
German Cancer Research Center,Heidelberg,Germany
,
Axel Benner
Affiliations:
German Cancer Research Center,Heidelberg,Germany
,
Dirk Hose
Affiliations:
University of Heidelberg,Heidelberg,Germany
,
Anna Jauch
Affiliations:
University of Heidelberg,Heidelberg,Germany
,
Lothar Kanz
Affiliations:
University Hospital of Tuebingen,Tuebingen,Germany
Hartmut Goldschmidt
Affiliations:
University of Heidelberg,Heidelberg,Germany
EHA Library. Weisel K. 06/16/18; 215594; PS1294
Dr. Katja C Weisel
Dr. Katja C Weisel
Contributions
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Abstract

Abstract: PS1294

Type: Poster Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 17:30 - 19:00

Location: Poster area

Background
Pomalidomide (POM) + dexamethasone (Dex) is a standard treatment in relapsed and refractory multiple myeloma (RRMM) resulting in an overall response rate (ORR) of approximately 30% and a median progression-free survival of 4.0 months (San Miguel et al., Lancet Oncol 2013). Patients responding to POM + Dex show extended progression-free (PFS) and overall survival (OS) (Moreau et al., Leuk Lymphoma 2016). Cyclophosphamide (CY) is an alkylating agent showing anti-myeloma activity with potential synergistic effects to immunomodulating agents (IMiDs) as POM and lenalidomide.

Aims
The GMMG-PERSPECTIVE trial (Eudra-CT No. 2013‐003678‐29) is a phase II multicenter investigator initiated trial in RRMM patients investigating efficacy when CY is added to POM + Dex standard treatment in case of primary progression or less than partial remission (PR) after 3 treatment cycles of POM + Dex. The primary objective of the trial is to demonstrate that the objective response rate (ORR) exceeds 30%, key secondary endpoints are PFS, time to next treatment (TTNT), OS and safety.

Methods
60 patients with RRMM after at least 2 prior treatment lines including bortezomib and lenalidomide and not responding to the last prior regimen were included. All patients were included in safety analyses. 59 patients were eligible for the intention-to-treat (ITT) analysis of primary and secondary endpoints. Patients received standard dose of POM + Dex (POM 4 mg day 1-21, Dex 40 mg day 1, 8, 15, 22 of a 28-day cycle, Dex 20 mg weekly in patients > 75 years). In case of no PR after 3 cycles and/or disease progression (PD) during cycle 1-3, CY in a dose of 500 mg/m² intravenously day 1 and 15 per cycle was added. Patients were treated until PD or unacceptable toxicity. ORR as primary endpoint was evaluated after a median follow-up of 20.1 months. After a median follow-up of 32.8 months PFS, PFS from start of CY, OS, TTNT as secondary endpoints and safety data were reported.

Results
60 patients were included into the trial. Median age was 67.0 (range 47-81) years, median number of prior treatment lines was 3 (2-5). 45% of evaluable patients had cytogenetic high-risk disease. ORR (≥ PR) was 39% (not significant with a lower 95% confidence bound of 29.2%). PR was reached in 14 (23.7%), very good partial remission (VGPR) in 7 (11.9%) and complete remission (CR) in 2 (3.4%) patients. 36/59 patients received CY after a median time of 2.9 months (1.1-4.4 months). At the time of addition of CY 16 patients had PD, 15 stable disease (SD) and 5 showed minimal response (MR). 13/36 patients with addition of CY to POM + Dex achieved a response: 8 PR (22.2%), 3 VGPR (8.3%), 2 CR (5.6%). Median PFS of the ITT population was 6.4 months. Median PFS from start of CY was 4.8 months. Median TTNT was 11.0 months. Median OS was 18.3 months. Main hematologic toxicities ³ grade 3 were neutropenia in 26 (43.3%), anemia in 16 (26.7%), leukopenia in 15 (25.0%) and thrombocytopenia in 9 (15.0%) patients. Main non-hematologic toxicities ³ grade 3 were pneumonia in 10 (16.7%) patients. All other toxicities ³ grade 3 were ≤ 5%.

Conclusion
In RRMM patients, addition of CY to standard POM + Dex treatment is able to overcome lack of response or primary resistance to POM + Dex in a marked proportion of patients. PFS, TTNT and OS of the IIT compares favorably with published data for POM + Dex alone. With a favorable toxicity profile of the triple combination, primary addition of CY to POM + Dex should be considered in future to further optimize efficacy and durability of responses in POM + Dex standard treatment.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Myeloma, Relapse, Treatment

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