Mantle cell lymphoma survival rates improving with new targeted therapies

Photomicrograph showing mantle cell lymphoma / Science Source
Photomicrograph showing mantle cell lymphoma / Science Source

Over the last year, oncologists have added new weapons to their arsenal against mantle cell lymphoma (MCL), an aggressive B-cell subtype of NHL that accounts for 6% of all cases of the disease.1

Currently, MCL is treated using combination chemotherapy or chemotherapy plus immunotherapy, followed by stem cell transplantation.  However, agents such as ibrutinib and lenalidomide have recently demonstrated an ability to improve progression-free survival (PFS) and overall survival (OS) by targeting B-cell receptor signaling.1

“We have gone from a 3-year survival rate to a median of 7 years for MCL,” said Thomas Witzig, MD, Professor of Medicine at the Mayo Clinic, Rochester, MN.  “Over the last year, we've added new drugs to the armamentarium and this has markedly improved survival rates.”

Evaluating the Effects of Bruton's Tyrosine Kinase Inhibition

Response rates to initial combination chemotherapy regimens are often very good in patients with MCL; however, relapse is very common. A recent phase 2 study by researchers at Ohio State University found that durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma and could produce an overall response rate of 68%.2 Ibrutinib inhibits Bruton's tyrosine kinase (BTK), which is a B-cell receptor signalling mediator essential for normal B-cell development. Inhibiting BTK with ibrutinib causes cell death and decreases cellular migration and adhesion in malignant B-cells. 

“Ibrutinib is very promising,” said senior study author Kristie Blum, MD, an associate professor of medicine and the head of the Ohio State University Comprehensive Cancer Center, Columbus, OH.  “It is certainly exciting because it is well tolerated and has a high activity rate.”

In this study, Dr. Blum and her colleagues looked at 111 patients with relapsed or refractory MCL who received ibrutinib orally.  The trial was conducted at 18 sites and the patients had received one to five prior treatments, which could include bortezomib.  The researchers found that 21% of patients achieved a complete response and 47% achieved a partial response.  The estimated median response duration was 17.5 months and the estimated median PFS was 13.9 months.  The median OS was not reached, but the estimated OS rate was 58% at 18 months.

“A lot of people get really aggressive treatment.  It is possible [that ibrutinib] could be used earlier in the course of the disease,” Dr. Blum said in an interview with ChemotherapyAdvisor.com.

Lenalidomide for Relapsed/Refractory MCL

The immunomodulatory agent lenalidomide has been shown to have consistent activity and a tolerable safety profile in patients with relapsed/refractory MCL. Dr. Witzig and his team conducted a pooled analysis to examine the efficacy and safety of this agent in 206 patients with relapsed/refractory MCL.  The researchers found that the overall response rate (ORR) with lenalidomide was 32%, with a median time to response of 2.1 months.3

In this pooled analysis, the median age of the patients was 67 years (range, 33-84 years) and 91% of the patients had stage 3/4 disease; the mean daily dose of lenalidomide was 21 mg. Among the 206 patients, 51% had received four or more prior treatment regimens and 76% had been previously treated with bortezomib.  Overall, results showed that 10% of the patients achieved a complete response and the median duration of response was 16.6 months.

“About a third of patients respond and they usually respond pretty quickly—within 2 months of taking the drug,” Dr. Witzig told ChemotherapyAdvisor.com.  “It is usually pretty tolerable.  Some people get a little fatigued, but it is certainly designed to be taken long-term and it has a good safety profile.” 

Dr. Witzig added that lenalidomide's mechanism of action is completely different from that of ibrutinib, and so the two agents may be able to be combined to produce even more benefits in some patients with MCL.

 

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