Imbruvica gives hope to rare blood cancer patients10 Aug 2015
Ibrutinib (Imbruvica) produced rapid and durable responses in heavily treated patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), according to an updated report of the safety and efficacy of an open-label phase 2 registration trial. Imbruvica is an oral inhibitor of Bruton tyrosine kinase.
"MCL, a rare type of non Hodgkin lymphoma, is not curable and relapse is common with the majority of patients dying from progressive disease (PD)," Michael Wang, MD, the University of Texas MD Anderson Cancer Center, Houston, Texas, and multi-center colleagues report in Blood.
"In addition, the commonly used chemotherapeutic regimens can cause myelosuppression that can make treatment particularly difficult in elderly patients [so] novel agents with improved efficacy and less toxicity are needed."
Characteristics of the enrolled patients
The study was an open-label multicenter, phase 2 study carried out at 18 sites in the US and Europe. Patients with relapsed or refractory MCL were enrolled without randomization and classified as either bortezomib-treated (2 or more cycles) or bortezomib-naive (fewer than 2 cycles or no prior treatment with bortezomib).
- The median age of the group was 68 years
- Almost half had a high-risk Mantle Cell Lymphoma International Prognostic Index score
- The median number of prior therapies was three (range one-five)
- All patients had failed to achieve at least a partial response (PR) to prior therapy or had progressed after the most recent treatment.
Patients were given fixed continuous doses of oral ibrutinib, 56 mg per day, until they progressed or experienced unacceptable toxicity.
Clinical results of the international trial
Among 111 patients with R/R MCL treated with oral ibrutinib, 560 mg once a day for a median of 8.3 months, the analysis of the data showed that:
- The overall response rate (ORR) was 67% with a median duration of response of 17.5 months
- Some 46% of patients were treated for longer than one year and 20% were treated for two years or longer
- 23% of patients achieved a complete response (CR)
- The median time to initial response for all patients was 1.9 months and the median time to a CR was 5.5 months
- The 24-month progression-free survival (PFS) rate was 31% and the overall survival (OS) rate at 24 months was 47%.
"There were no apparent differences in ORRs with respect to tumor volume," investigators observe. However, CR rates as well as duration of response, OS, and PFS were generally higher for patients with less bulky tumors, they add.
- ORR was also similar in patients who had received prior bortezomib at 65% as well as for those who had received prior lenalidomide at an ORR of 59%.
- For patients whose best response was a PR, the estimated median duration of response was 14.9 months and for those who achieved a CR, the median duration of response had not been reached at the point of the current analysis.
What about the adverse events?
The most common adverse events included:
- diarrhea, which occurred in 54% of patients;
- fatigue in 50% of patients,
- nausea in 33% of patients, and
- Dyspnea in 32% of patients.
The most common grade 3 or higher hematologic adverse events were:
- neutropenia in 17% of patients,
- thrombocytopenia in 13% of patients, and
- Anemia in 11% of patients.
No hematologic event led to the discontinuation of ibrutinib but the dose was reduced in 7 cases of neutropenia.
The most frequent grade three or higher infections included:
- urinary tract infection, and
But these occurred in only a small minority of patients.
Grade three or higher bleeding events included hematuria and subdural hematoma at 2% in each instance.
“The data continue to demonstrate a favorable benefit-risk profile of ibrutinib”
"The prevalence of infection, diarrhea, and bleeding was highest for the first six months of therapy and less thereafter," the investigators observed.
Eighteen patients or 16% of the cohort experienced grade five (fatal) adverse events within 30 days of the last dose of ibrutinib, eight of which were reported as MCL by investigators and six of which were considered to be associated with disease progression.
"In summary, we have presented extended (26.7 month follow-up) data which continue to demonstrate a favorable benefit-risk profile of ibrutinib in R/R MCL patients," investigators conclude. "And approximately one-third of patients remain progression-free at 24 months."Source: MedPage Today