March 28, 2018
2 min read

Ibrutinib plus venetoclax improves outcomes in poor-prognosis mantle cell lymphoma

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Ibrutinib plus venetoclax improved outcomes among patients with mantle cell lymphoma predicted to have poor outcomes when treated with standard therapies, according to study findings.

“Until recently, patients with chemotherapy-resistant [mantle cell lymphoma] had few effective treatment options,” Constantine S. Tam, MBBS, MD, FRACP, hematologist and disease group lead at Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues wrote. “Recent treatment advances have included the emergence of targeted therapies for B-cell neoplasms. Ibrutinib [Imbruvica, Pharmacyclics] and venetoclax [Venclexta, AbbVie] are two of the most active agents in the treatment of chronic lymphocytic leukemia and mantle cell lymphoma.”

The researchers performed a single-group, phase 2 study of 24 patients aged 47 to 81 years with either relapsed or refractory mantle cell lymphoma (n = 23) or treatment-naive mantle cell lymphoma (n = 1), comparing patients with historical controls. Patients received up to six previous treatments. Most (75%) had a high-risk prognostic score and half had aberrations of TP53.

Patients began with 560 mg per day of ibrutinib monotherapy — a Bruton’s targeted kinase inhibitor — and starting at 4 weeks received stepwise, weekly increasing doses of up to 400 mg per day of venetoclax, a BCL2 inhibitor. Treatment continued until either an unacceptable level of adverse events or disease progression.

Researchers used flow cytometry in bone marrow and allele-specific oligonucleotide-polymerase chain reaction in blood to assess minimal residual disease.

Rate of complete response at week 16 served as the main outcome.

CT showed a complete response rate at week 16 of 42%. This was significantly greater than the historical result of 9% with ibrutinib monotherapy (P < .001).

When assessed with PET, the complete response rate was 62% at 16 weeks and 71% overall.

Flow cytometry confirmed clearance of minimal residual disease among 67% of patients, whereas allele-specific oligonucleotide-polymerase chain reaction confirmed clearance among 38%.

Through time-to-event analysis, researchers estimated 78% of patients with a response had ongoing response at the 15-month mark.

Two patients experienced tumor lysis syndrome. Most patients experienced diarrhea (83%), fatigue (75%), and nausea or vomiting (71%), which were generally low grade.

“Ibrutinib and venetoclax can be administered in combination, with side effects that are acceptable to both patients and physicians, and the combination is highly active,” the researchers wrote. “... Such outcomes appear to be substantially better than those that have been reported for ibrutinib or venetoclax monotherapy.” – by Andy Polhamus


Disclosures: Tam reports grant support and personal fees AbbVie and Janssen during the conduct of the study, as well as personal fees from Pharmacyclics outside the submitted work. Please see the full study for all other authors’ relevant financial disclosures.