ATLANTA – Lenalidomide, already an important agent in the treatment of multiple myeloma, is also flexing its muscles against non-Hodgkin’s lymphomas, reported researchers in two clinical trials presented at the annual meeting of the American Society for Hematology.

In a phase II study, lenalidomide (Revlimid) added to CHOP chemotherapy and rituximab (LR-CHOP21) produced a 92% overall response rate in elderly patients with untreated diffuse large B cell lymphoma (DLBCL), reported Dr. Annalisa Chiappella on behalf of the Italian Lymphoma Foundation in Alessandria, Italy.

"With a still limited follow-up, our data compare favorably with historical R-CHOP21 data, with a 2-year survival of 92% and a 2-year progression-free survival of 73%. LR-CHOP21 is able to induce a high 2-year progression-free survival of 65% also in poor-risk patients," Dr. Chiappella said.

In a separate study, single-agent lenalidomide also showed efficacy against relapsed/refractory mantle cell lymphoma (MCL), producing a 28% overall response rate for a median duration of 16.6 months, reported Dr. Andre Goy, chief of the lymphoma division at the John Theurer Cancer Center at Hackensack (N.J.) University Medical Center.

"This was a heavily pretreated population with a median of four prior therapies and a range of two to 10. Two-thirds were refractory to bortezomib [Velcade], more than half had a high tumor burden, one-third of the patients had bulky disease, and one-third had received prior transplants," Dr. Goy said.

CHOP add-on

In the Italian study, Dr. Chiappella and her colleagues looked at LR-CHOP21 in 49 patients (median age 69 years) with DLBCL. Nine of the patients had been treated with LR-CHOP21 at the maximum tolerated dose in phase I of the study.

The regimen consisted of six cycles of CHOP (cyclophosphamide, hydroxydaunomycin [doxorubicin], Oncovin [vincristine], and prednisone) plus rituximab at a dose of 375 mg/m², and lenalidomide at a dose of 15 mg daily on days 1-14 of each 21-day cycle.

Of the 294 total planned cycles of LR-CHOP21, 277 (94%) were administered. Some patients required a dose or a day reduction of lenalidomide, some received R-CHOP21 only, and some did not receive all planned cycles.

The final response, assessed after six cycles, included a complete response in 42 patients, a partial response in 3, no response in 3, and 1 death, for an overall response rate of 92%, At a median follow up of 22 months, the 2-year overall survival rate was 92%, which compares favorably with the 70% survival rate seen in historical controls treated with R-CHOP21 only, Dr. Chiappella said.

Of the four patient deaths, one was due to trauma, one to sepsis and multiple organ failure in a patient who had a complete response and had been off treatment for 6 months, one was due to heart failure, and one was from lymphoma progression.

The 2-year progression-free survival at 22 months’ median follow-up was 73%. The rate in R-CHOP21-treated historical controls was 57%.

Based on International Prognostic Index (IPI) risk, 2-year progression-free survival was 84% in patients with low- or intermediate-risk disease, and 65% in patients with intermediate/high-risk or high-risk disease.

Grade 3 or 4 adverse events in the per-protocol group included neutropenia (9% grade 3, 22% grade 4), febrile neutropenia (3%, 1%), leukocytopenia (15%, 13%), and thrombocytopenia (6%, 7%).

"These encouraging data warrant a future phase III randomized trial comparing LR-CHOP21 and R-CHOP21 in elderly patients with untreated DLBCL," Dr. Chiappella said.

MCL rescue

Dr. Goy and his colleagues looked at single-agent lenalidomide in patients with MCL who experienced disease relapse, progression, or who were refractory to bortezomib in the EMERGE trial (MCL-001 study).

In the phase II open-label study, 134 patients with MCL received lenalidomide 25 mg/day for 21 days out of every 28, with CT scans every two cycles until disease progression or unacceptable toxicities. The patients had to have failed prior anthracycline- or mitoxantrone-based therapy, cyclophosphamide, rituximab, and bortezomib.

The overall response rate by central review was 28%, with 8% of patients having a complete response or complete response unconfirmed (CR/CRu), 20% having a partial response, 29% having stable disease, and 26% experiencing disease progression.

The median time to response was 2.2 months, median time to CR/CRu was 3.7 months, median progression-free survival was 4 months, and median overall survival was 19 months at a median follow-up of 9.9 months. The median duration of response was more than 16 months, with the longest response more than 29 months at the time of data cutoff in July 2012.

The most common grade 3 or 4 adverse event was myelosuppression, consistent with the known safety profile of lenalidomide in non-Hodgkin’s lymphoma, Dr. Goy said.

Both Dr. Chiappella’s and Dr. Goy’s studies were supported in part by Celgene, maker of lenalidomide. Dr. Chiappella reported having no relevant disclosures. Dr. Goy is on Celgene’s speakers bureau.

Lenalidomide branches out to lymphoma therapy