Lenalidomide is an orally active immunomodulatory drug effective in the treatment of multiple myeloma. We evaluated the toxicity and efficacy of MPR combination in a phase I/II study. Patients with newly diagnosed symptomatic multiple myeloma who were not candidates or refused stem cell transplantation were eligible. Treatment consisted of M and P on days 1 – 4 and R on days 1 – 21 in a 28 day cycle. All patients received aspirin 325 mg a day. Routine antibacterial prophylaxis was not used. Patients were accrued in cohorts of 3 at dose level 0 (M 5mg/m 2/d P 60 mg/m2/d R 10 mg/d) and level 1 (M 8mg/m2/d P 60 mg/m2/d R 10 mg/d). Patients were followed for at least 2 cycles to assess Dose Limiting Toxicity (DLT). G/GM-CSF use was not allowed in the first 2 cycles unless DLT had occurred. DLT was defined as occurrence of at least grade (G) 4 hematologic toxicity, G3 febrile neutropenia, or G 3 non-hematologic toxicity in the first two cycles. Failure to start the next cycle within 7 days of day 1 due to toxicity also constituted DLT.

Results: 7 patients have been accrued (4 at dose level 0 {one patient had to be replaced} and 3 at dose level 1). 4 were males. ECOG performance status was 0 or1 (2 and 4 patients). Median age was 74 yrs, range 72 – 85. Between 3 and 10 cycles (median 4) have been administered at the time of this reporting. The following G3 or higher toxicities were encountered and considered at least possibly related to treatment: 2 patients at level 0 had G3 neutropenia. Of the three patients at dose level 1, there was 1 G4 neutropenia, 1 G4 thrombocytopenia, 1 G3 hyperglycemia and 1 G4 vascular access device related thrombosis. Responses were defined by EBMT/IBMTR criteria. 1 had a complete remission (after 3 cycles), 4 had partial remission (at least 50% reduction in monoclonal protein) and 1 had minimal response (after 3 cycles). Due to 3 DLT’s in dose level 1, dose level 0 was chosen for phase II of the study.

Conclusion: M 5 mg/m2, P 60 mg/m2 and R 10 mg combination is well tolerated and appears effective in patients with multiple myeloma. These results are similar to the experience reported by

Palumbo et al (
Blood
2005
,
106
(11):
abst 785
)
although a stricter definition of DLT was used in our study. Escalation of R dose in combination with M 5 mg/m2, P 60 mg/m2 may be possible and improve responses. Updated data will be presented.

Topics:
hematopoietic stem cell transplantation, lenalidomide, melphalan, multiple myeloma, prednisone, toxic effect, neutropenia, antibacterial prophylaxis, aspirin, complete remission

Disclosures: Lenalidomide not approved for treatment of newly diagnosed patients with myeloma.; Celegene Corp.

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2006, The American Society of Hematology
2006
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