Home Lymphoma Ibrutinib Effectiveness in Symptomatic, Previously Treated Waldenström Macroglobulinemia

Ibrutinib Effectiveness in Symptomatic, Previously Treated Waldenström Macroglobulinemia

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Among a subset of patients with previously treated Waldenström macroglobulinemia (WM), ibrutinib appears to be promising, and may lead to long-term disease control, according to study results published in the Journal of Clinical Oncology.

Previous research has shown that MYD88 and CXCR4 mutations are common in patients with WM, with mutated (Mut) MDY88 noted in up to 97% of patients. MDY88Mutis  linked to Bruton tyrosine kinase (BTK) activation via the hematopoietic cell kinase (HCK). CXCR4Mut, by contrast, is found in up to 40% of patients, and is associated with resistance to ibrutinib, an inhibitor of both BTK and HCK.

Initial data from a study evaluating the safety and efficacy of ibrutinib in previously treated, symptomatic WM showed an overall response rate of 90%. In the present paper, the authors reported both the long-term efficacy of ibrutinib in this setting, and the impact of MDY88Mutand CXCR4Muton treatment response.

Overall, 63 patients were enrolled and received ibrutinib monotherapy. The median age was 63 years (range, 44-86), 48 (76%) patients were men, and the median number of prior therapies was 2 (range, 1-9). In addition, 14 (22%) patients, 27 (43%) patients, and 22 (35%) patients had International Prognostic Scoring System for Waldenström Macroglobulinemia (IPSSWM) measures of low, intermediate, and high, respectively. Of the cohort, 36 patients had mutated MDY88Mutand wild type (WT) CXCR4, 22 patients had both MDY88Mut/CXCR4Mut, and 4 patients had WT of both genes.

The median follow-up period was 59 months. Overall, 57 (90.5%) patients had a response: 7 (11.1%) had a minor response, 31 (49.2%) had a partial response, and 19 (30.2%) had a very good partial response. The most responses were reported in patients with MDY88Mut/CXCR4WT. Of note, the 4 patients with MDY88WT/CXCR4WThad either no response (50%) or minor response (50%).

The overall response rate in MDY88Mut/CXCR4WT was 100%, among which 18 (50%) were partial responses and 17 (47.2%) were very good partial responses. Among patients with mutated MDY88Mut/CXCR4Mut, the overall response rate was 86.4%, among which 13 (59.1%) were partial responses and 2 (9.1%) were very good partial responses.

Overall, the median 5-year progression-free survival (PFS) rate was not reached but was 70% and 38% for patients with MDY88Mut/CXCR4WT and MDY88Mut/CXCR4Mut, respectively (P =.02). The 5-year overall survival rates were 87% for the entire cohort, and 93% and 80% for patients with MDY88Mut/CXCR4WT and MDY88Mut/CXCR4Mut, respectively. Patients with MDY88WT had a median PFS of 0.4 years.

Grade 3 or worse adverse events that may have been related to ibrutinib treatment included neutropenia (15.9%), thrombocytopenia (11.1%), and pneumonia (3.2%). The majority of neutropenic and thrombocytopenic events occurred in patients treated with 3 or more prior therapies.

“A key finding was the long durability for ibrutinib response, with the median PFS [longer than] 5 years. By comparison with other agents and combinations used in relapsed or refractory WM, the median PFS observed with ibrutinib is superior,” the authors noted.

“Prospective, randomized studies against other commonly used treatment options, such as bendamustine and rituximab, other BTK-inhibitors, and combinations that include CXCR4 or BCL2 inhibitors, are needed to further define the optimal use of ibrutinib in WM management,” the investigators concluded.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Treon SP, Meid K, Gustine J, et al. Long-term follow-up of ibrutinib monotherapy in symptomatic, previously treated patients with Waldenström macroglobulinemia. J Clin Oncol. Published online September 15, 2020. doi:10.1200/JCO.20.00555

https://www.hematologyadvisor.com/home/topics/lymphoma/ibrutinib-effectiveness-in-symptomatic-previously-treated-waldenstrom-macroglobulinemia/

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