Lenalidomide consolidation after ASCT induces antitumor effect

New Orleans—Lenalidomide consolidation after autologous transplantation for myeloma is not only feasible, but can decrease residual tumor mass and lead to an antitumor effect.

High-dose therapy (HDT) supported with autologous stem cell transplantation (ASCT) is a standard treatment option for myeloma. But residual disease, responsible for relapse, is always present after single or double transplantation, said Michel Attal, MD, of Hopital Purpan in Toulouse, France.

He reported the initial analysis of an Intergroupe Francophone Du Myelome study on lenalidomide consolidation at the American Society of Hematology annual meeting held December 5-8.

Different strategies have been used to decrease residual disease after ASCT, including improvements in the induction regimen or the conditioning regimen, or by adding consolidation treatment post-ASCT.

Maintenance therapy with thalidomide after ASCT has been shown to reduce residual disease and improve event-free survival and overall survival. However, a high incidence of neuropathy induced by thalidomide is a major limiting factor. Lenalidomide, the analog of thalidomide without neurologic toxicity, is an attractive candidate for consolidation/maintenance treatment after HDT, he said.

Dr Attal and colleagues conducted a study of 614 myeloma patients under the age of 65 years with non-progressive disease. All patients had firstline ASCT performed less than 6 months previously.

A total of 572 patients received consolidation treatment with lenalidomide 25 mg/day, 21 days per month for 2 months, followed by a maintenance treatment with lenalidomide 10 to 15 mg/day until relapse or a maintenance treatment with placebo until relapse.

The patients, mean age 57 years, had ISS I 33%, II 25%, III 42%, with a median beta-2 microglobulin level of 3.3 mg/L.

FISH analysis found del 13 in 41%,  t(4;14) in 8%, and del 17p in 10% of patients.

Most patients had an induction regimen with vincristine/adriamycin/dexamethasone (49%) or bortezomib/dexamethasone (44%). Three quarters of patients received a single ASCT.  The mean interval between ASCT and lenalidomide consolidation was 4 months.
 
Consolidation with lenalidomide was safe, Dr Attal said. During consolidation 5% of the 572 patients had a serious adverse event (SAE) and 15% had grade 3/4 toxicities, primarily hematologic events (12%).

With lenalidomide consolidation, 80% of patients could receive the planned 2 cycles of consolidation, 15% could receive the 2 cycles with a reduced dose, and 5% had to discontinue lenalidomide. The median length of consolidation therapy was 42 days.

The response rate before consolidation based on investigator assessment of 504 patients was 38% very good partial response (VGPR) and 35% partial response or stable disease, and “18% of patients with evaluable disease showed improvement,” Dr Attal said. An independent review committee assessment of 361 patients found a 31% improvement in response.

Prognostic factors to achieve VGPR after consolidation included VGPR response after induction, bortezomib-dexamethasone induction, and one line of induction.
 
Dr Attal said, “[C]onsolidation treatment with lenalidomide alone after stem cell transplant is feasible with a low rate of SAE, is associated with a decrease of the residual tumor mass, and is probably responsible for this antitumor effect since this was observed in a median of 7 months after transplant.”

The maintenance effect of lenalidomide will be evaluated in May 2010, he added.