New Jersey's John Theurer Cancer Center has made substantial progress on two oral formulations to treat refractory mantle-cell lymphoma (MCL), a particularly challenging form of non-Hodgkin's lymphoma that leads to chemoresistance over time. The organization published two studies recently demonstrating the success of the two novel treatments.
The first-ever oral drug for MCL, lenalidomide, which is a thalidomide analog, showed in a pivotal Phase II study to be effective with a 28% objective response rate over a median of 16.6 months, a result that co-author Andre Goy told FierceDrugDelivery "is very impressive in that setting," and which the cancer center called a breakthrough in the treatment of MCL. Because MCL leads to chemoresistance, it's also important that this occurred reliably in patients who failed prior therapies, Goy said. The drug, now marketed by Celgene ($CELG) as Revlimid, is only the second drug ever approved for MCL and the first oral version, as published in the Journal of Clinical Oncology.
"(L)enalidomide has many properties, and the actual mechanism is not well identified, and relative parts of each mechanism among diseases and patients might vary," Goy wrote in an email. "Practically, the immunomodulator function is likely the most important, stimulating T cells and NK cells as well as helping to restore immunological recognition of tumor cells, which hide from the immune system. The immunological synapses between tumor cells and lymphocytes, or killer cells, is improved after exposure to lenalidomide in vivo."
A second study published in the New England Journal of Medicine brought the cancer center together with the MD Anderson Cancer Center and others, according to a release, to study the oral Johnson & Johnson ($JNJ) drug ibrutinib, currently under the FDA's priority review. The treatment is the first Bruton's tyrosine kinase inhibitor, putting the compound in a new class of drugs that target and restrain the B-cell receptor pathway. This pathway has been found to aid in lymphoma cells' survival, Goy said.
"The Phase II study showed a response rate of 68% (75 patients) with complete response rate of 21% even in patients heavily pretreated or who had received prior bortezomib, and the estimated median response duration was 17.5 months," Goy wrote. "This provides another new oral option in the future if approved and then offers great opportunities for combinations."
- here's the release
- read the Journal of Clinical Oncology abstract
- and the NEJM abstract