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A Subset of Revlimid/Dexamethasone vs Dexamethasone Alone After Thalidomide Therapy in Relapsed/Refractory Myeloma
By Michael Wang, MD

This prospective analysis of 704 patients treated in two randomized Phase III trials of Rev/dex vs. dex/placebo was conducted to see if prior thalidomide therapy would make patients' myeloma insensitive to Revlimid. The analysis determined that although Revlimid is an analog of thalidomide, it is still effective after thalidomide exposure.

ABSTRACT:Lenalidomide in Combination with Dexamethasone Was More Effective Than Dexamethasone in Patients Who Have Received Prior Thalidomide for Relapsed or Refractory Multiple Myeloma. Session Type: Poster Session, Board #782-III

Michael Wang, Robert Knight, Melitios Dimopoulos, David Siegel, S. Vincent Rajkumar, Thierry Facon, Raymond Alexanian, Zhinuan Yu, Jerome Zeldis, Marta Olesnyckyj, Donna Weber Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Celgene Corporation, Summit, NJ, USA; General Alexandras Hospital, Athens, Greece; Hackensack University Medical Center, Hackensack, NJ, USA; Mayo Clinic, Rochester, MN, USA; Hospital Claude Huriez, Lillie, France

Lenalidomide (Len), an analog of thalidomide (thal) is a novel, oral, immunomodulatory agent that is effective against multiple myeloma (MM). In 2 prospective, randomized, double-blind, placebo-controlled Phase III trials. Len with dexamethasone (Dex) induced a significantly higher overall response rate (OR) and complete remission rate (CR), as well as longer time-to-progression (TTP) in comparison with Dex alone. This prospective analysis assessed whether prior thalidomide exposure might induce subsequent resistance to Len/Dex. We evaluated 704 patients (pts) from both trials (MM009, MM010) who had relapsed or refractory multiple myeloma, had not been resistant to Dex and were randomized to receive either oral Len (25 mg daily for 3 weeks every 4 weeks) plus Dex (40 mg on days 1-4, 9-12, 17-20 every 4 weeks for 4 cycles) or placebo plus Dex. Two hundred seventy four pts (39%) received prior thal, while 430 (61%) had not. The prior thal exposed pts and thal-naive pts were similar in regard to age, Beta-2-microglobulin, hemoglobin, serum M protein, albumin and history of previous transplantation. The frequency of deep venous thrombosis and pulmonary embolism (DVT/PE) with prior thal exposure was higher at 14% with Len/Dex than 4% with Dex alone (p < 0.01). However, the frequency of DVT/PE with no prior thal exposure was similar at 8% with Len/Dex to 6% with Dex alone (p = 0.49). In the prior thal pts, severe neuropathy occurred in 4% with Len/Dex, not significantly different from the 1% with Dex alone (p=0.2). The pooled data from all 704 pts showed that pts treated with Len/Dex, compared with those treated with Dex alone, had superior median Time-To-Progression (TTP) (48 vs 20 weeks) and OR (60% vs 22%, p <0.001). Similarly, among the subgroups exposed or not exposed to thal, Len/Dex was superior to Dex alone in OR and TTP. For the 126 patients who received prior thal, the OR with Len/Dex was significantly less (43%) among 54 Pts resistant to thal than that observed for 72 Pts who had been sensitive to thal (63%, p < 0.05). Multivariate analysis using Cox proportion hazards model indicated that after controlling for treatment (Len/Dex vs Dex) and baseline disease characteristics, independent and significant predictors of shorter TTP included prior thal exposure, duration of myeloma and number of prior therapies. Len in combination with Dex was more effective than Dex in patients with relapsed or refractory multiple myeloma despite prior thal exposure. Results with Len/Dex were superior for those not exposed to thal, suggesting some, but not complete, cross resistance between Len and thal.

Len/Dex vs Dex with or without Prior Thal
Thal (N=274) No Thal (N=430)
LD D p LD D p
Intent-to-Treat (n) 126 148 227 203
TTP (med. weeks) 36.9 19.9 <.001 61.3 20.4 <.001
OR (%) 54.0 14.9 <.001 63.4 27.6 <.001
PR (%) 42.1 12.8 <.001 32.2 23.2 <.05
NCR (%) 4.0 0.7 <.001 13.2 2.0 <.001
CR (%) 7.9 1.4 <.01 18.1 2.5 <.001

Abstract #3553 appears in Blood, Volume 108, issue 11, November 16, 2006

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