Tag: MCL

Ibrutinib is Effective Therapy for Patients with Previously Treated Mantle Cell Lymphoma

On June 20, 2013, the exciting results of a phase 2 clinical trial of ibrutinib in patients with previously treated mantle cell lymphoma (MCL) were published in the New England Journal of Medicine. Ibrutinib is an oral inhibitor of Bruton’s Tyrosine Kinase (BTK), an enzyme that plays a critical role in the survival and growth of some lymphomas, including MCL, CLL/SLL, follicular lymphoma, DLBCL, and Waldenstrom’s macroglobulinemia.

In this trial, 111 patients with MCL received oral ibrutinib at a dose of 560 mg daily. Despite a high number of prior therapies, 68% of patients experienced a significant response to ibrutinib, including 21% of patients experiencing a complete response. The estimated average response duration was almost 18 months. Overall, the treatment was well tolerated. The study authors concluded that ibrutinib is highly effective in treating relapsed and refractory MCL, achieving responses comparable to intensive chemotherapy regimens with less toxicity. Weill Cornell’s Dr. Peter Martin, one of the study’s lead authors, commented, “It has been tremendously gratifying to be able to offer ibrutinib to our patients with mantle cell lymphoma. We are all working hard so that this drug can be made available to all patients in the near future.”

The Lymphoma Program at Weill Cornell will be participating in an early access trial that will help provide ibrutinib to patients with MCL pending its official FDA approval.  Look to this space for further updates.

ASCO 2013: Single-agent Lenalidomide Produces Promising Results in Relapsed/Refractory Mantle Cell Lymphoma

jruanBy Jia Ruan, MD, PhD

Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma (NHL) characterized by a short remission duration to standard therapies, poor prognosis, and median overall survival of 4-5 years. The immunomodulatory agent lenalidomide has consistently exhibited a tolerable level of safety in multiple phase II studies of relapsed/refractory aggressive NHL and MCL post-bortezomib.  At the recent 2013 annual meeting of the American Society of Clinical Oncology, Dr. Thomas E. Witzig of the Mayo Clinic presented results from a combined analysis of multiple phase II trials testing the efficacy and safety of single-agent lenalidomide in relapsed/refractory MCL patients.

Of the 206 patients with relapsed/refractory MCL the overall response rate with lenalidomide was 32%, with a median time to response of 2.1 months and median duration of response of 16.6 months. Kaplan-Meier estimates for median progression free survival and overall survival were 5.4 and 23.9 months, respectively. Mean daily dose of lenalidomide was 21 mg.  Grade 3/4 adverse events included neutropenia (44%), thrombocytopenia (29%), anemia (11%), and fatigue (7%), other side effects included tumor flare reaction (7%), venous thromboembolic events (7%), and invasive second primary malignancies (3%).

This study adds to the growing body of literature supporting the promise of lenalidomide for treating patients with MCL.  At the Weill Cornell Lymphoma Program these breakthroughs are augmented by our own trials exploring the utility of lenalidomide in treating patients with MCL.

Update: this study is closed to enrollment. 

The Weill Cornell Lymphoma Program is now enrolling patients in a new, investigator-initiated phase II study of lenalidomide in combination with rituximab in patients with previously untreated MCL (NCT01472562). The purpose of the study is to test the synergy of combining lenalidomide, a biological agent that targets the tumor micro-environment, with rituximab, an antibody that targets lymphoma cells. By including a maintenance phase of lenalidomide and rituximab therapy, we hope to improve treatment effectiveness and maintain quality of life for patients.

This is an outpatient treatment strategy because lenalidomide, the study medication, can be taken at home.  After the first month on study, patients will be seen in clinic on average once a month.  The study has two phases:

Induction Phase, Weeks 1-48:

  •  Treatment dose lenalidomide taken by mouth on days 1-21 of a 28-day cycle for 12 cycles
  •  Rituximab infusion for a total of 9 doses

Maintenance Phase, Week 49 until disease progression or for a maximum of 5 years from study entry:

  • Maintenance dose lenalidominde taken by mouth on days 1-21 of a 28-day cycle
  • Rituximab infusion one dose every 8 weeks

Lenalidomide Approved for Mantle Cell Lymphoma Patients by FDA

Today, June 5 the FDA approved lenalidomide capsules for the treatment of patients with mantle cell lymphoma (MCL), who have experienced relapse or progression after receiving two prior therapies including bortezomib.

According to the FDA press release:

“The approval was based a single-arm, multicenter clinical trial enrolling 134 patients with mantle cell lymphoma who have relapsed after or were refractory to bortezomib or a bortezomib-containing regimen. All 134 patients received prior treatment with bortezomib and 60% were documented to have disease refractory to bortezomib therapy. Patients received a median of 4 prior therapies for MCL. The median age was 67 years, 81% were male, 96% were Caucasian, and 61% had MCL for at least 3 years.

The efficacy endpoints were overall response rate (ORR) and duration of response (DOR). The ORR was defined as the proportion of patients whose best response was complete response (CR), complete response unconfirmed (CRu), or partial response (PR). In the 133 patients who were evaluable for efficacy, the ORR was 26% (95% CI: 18.4, 33.9). CR or CRu was achieved by 9 patients (7%) and 25 patients (19%) achieved a PR. The median DOR for the 34 patients who achieved a CR, CRu, or PR was 16.6 months (95% CI: 7.7, 26.7).”

Here at the Weill Cornell Lymphoma Program we will endeavor to follow up with any further announcement regarding this new development.