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Poor outcomes likely for ibrutinib-resistant patients with mantle cell lymphoma
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Patients with mantle cell lymphoma who experience progression after ibrutinib treatment likely will not respond to salvage chemotherapy, according to results of a retrospective review.
Ibrutinib (Imbruvica; Pharmacyclics, Janssen), an oral Bruton’s tyrosine kinase inhibitor, has shown excellent efficacy in the treatment of mantle cell lymphoma. Results of a prior phase 2 trial showed an overall response rate of 68% and a median duration response of 17.8 months in this patient population.
However, researchers observed both primary and secondary resistance to ibrutinib, and outcomes in those patients were not well documented.
Chan Yoon Cheah, MD, clinical fellow in the department of lymphoma and myeloma at The University of Texas MD Anderson Cancer Center, and colleagues conducted a retrospective, single-institution study of patients with mantle cell lymphoma who were treated with ibrutinib and subsequently stopped therapy. The researchers measured patients’ response to salvage therapy and aimed to identify prognostic factors.
The analysis included 42 patients treated at MD Anderson from 2011 to January 2014, all of whom had been treated with ibrutinib but eventually discontinued use. Reasons for discontinuation included disease progression (n = 28), toxicity (n = 6), receipt of elective stem cell transplantation in remission (n = 4) and withdrawal of content to treatment (n = 4).
The median age was 69 years and 83% of the patients were men. The median number of prior treatments was two (range, 1-8) and the median time from initial diagnosis of mantle cell lymphoma to start of ibrutinib treatment was 3 years (range, 0.5-15.5 years). Patients received a median of 6.5 cycles (range, 1-43) of ibrutinib.
From the overall population, 31 patients experienced disease progression and underwent salvage chemotherapy. In this subgroup, the overall response rate was 32% and the complete response rate was 19%.
After a median follow-up of 10.7 months (range, 2.4-38.9), median OS was 8.4 months and the estimated 1-year OS was 22.1% (95% CI, 8.3-40.2).
“If patients fail ibrutinib, only one-third of them respond to their next line of treatment,” Cheah told HemOnc Today. “Those who do respond experience only brief remissions and have poor outcomes, irrespective of stem cell transplantation.”
Outcomes also were mixed in the cohort of patients who underwent stem cell transplantation.
Among those receiving allogenic stem cell transplantation, three had died — the first after 6 days of pneumonia, a second at 86 days after transplant from systemic and central nervous system progression, and a third at 129 days after transplant from acute graft-versus-host disease. Two other patients remained alive and in remission, one at 7 months post-transplant and the other at 10 months post-transplant.
Two patients underwent autologous stem cell transplantation. One died of disease progression and the other remained alive in remission at 4 months after transplant.
“Considering recent evidence suggesting the presence of subclonal heterogeneity in patients with mantle cell lymphoma, our findings suggest that in such patients, ibrutinib exposure may have selected an aggressive chemo-refractory clone,” Michael Wang, MD, professor in the department of lymphoma and myeloma at The University of Texas MD Anderson Cancer Center, a researcher on the study, told HemOnc Today. “A concerted effort to better understand the mechanisms of resistance to ibrutinib is critical for us to prevent and overcome it and improve the survival of the increasing number of patients who will find themselves in this situation.” – by Anthony SanFilippo
For more information:
Chan Yoon Cheah, MD, and Michael Wang, MD, can be reached The University of Texas MD Anderson Cancer Center, Department of Lymphoma/Myeloma, 1515 Holcombe Blvd., Houston, TX 77098.
Disclosure: The researchers report grant support from Pharmacyclics and Janssen Biotech.
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